DOPAMINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Dopamine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84579-4 1. Dopamine-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on dopamine. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON DOPAMINE ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Dopamine ...................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 63 The National Library of Medicine: PubMed ................................................................................ 91 CHAPTER 2. NUTRITION AND DOPAMINE .................................................................................... 139 Overview.................................................................................................................................... 139 Finding Nutrition Studies on Dopamine................................................................................... 139 Federal Resources on Nutrition ................................................................................................. 145 Additional Web Resources ......................................................................................................... 145 CHAPTER 3. ALTERNATIVE MEDICINE AND DOPAMINE .............................................................. 147 Overview.................................................................................................................................... 147 National Center for Complementary and Alternative Medicine................................................ 147 Additional Web Resources ......................................................................................................... 167 General References ..................................................................................................................... 172 CHAPTER 4. DISSERTATIONS ON DOPAMINE ................................................................................ 173 Overview.................................................................................................................................... 173 Dissertations on Dopamine........................................................................................................ 173 Keeping Current ........................................................................................................................ 178 CHAPTER 5. PATENTS ON DOPAMINE........................................................................................... 179 Overview.................................................................................................................................... 179 Patents on Dopamine................................................................................................................. 179 Patent Applications on Dopamine ............................................................................................. 196 Keeping Current ........................................................................................................................ 230 CHAPTER 6. BOOKS ON DOPAMINE .............................................................................................. 231 Overview.................................................................................................................................... 231 Book Summaries: Federal Agencies............................................................................................ 231 Book Summaries: Online Booksellers......................................................................................... 232 Chapters on Dopamine............................................................................................................... 235 CHAPTER 7. PERIODICALS AND NEWS ON DOPAMINE ................................................................ 241 Overview.................................................................................................................................... 241 News Services and Press Releases.............................................................................................. 241 Academic Periodicals covering Dopamine ................................................................................. 243 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 245 Overview.................................................................................................................................... 245 U.S. Pharmacopeia..................................................................................................................... 245 Commercial Databases ............................................................................................................... 246 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 251 Overview.................................................................................................................................... 251 NIH Guidelines.......................................................................................................................... 251 NIH Databases........................................................................................................................... 253 Other Commercial Databases..................................................................................................... 255 The Genome Project and Dopamine........................................................................................... 255 APPENDIX B. PATIENT RESOURCES ............................................................................................... 261 Overview.................................................................................................................................... 261 Patient Guideline Sources.......................................................................................................... 261 Finding Associations.................................................................................................................. 263 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 265 Overview.................................................................................................................................... 265
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Preparation................................................................................................................................. 265 Finding a Local Medical Library................................................................................................ 265 Medical Libraries in the U.S. and Canada ................................................................................. 265 ONLINE GLOSSARIES................................................................................................................ 271 Online Dictionary Directories ................................................................................................... 271 DOPAMINE DICTIONARY ........................................................................................................ 273 INDEX .............................................................................................................................................. 363
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with dopamine is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about dopamine, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to dopamine, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on dopamine. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to dopamine, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on dopamine. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON DOPAMINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on dopamine.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and dopamine, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “dopamine” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Dopamine in Gastrointestinal Diseases Source: Digestive Diseases and Sciences. 35(9): 1153-1161. September 1990. Summary: Dopamine is an important enteric neuromodulator. In this article, the authors review the data that support a role for dopaminergic involvement in experimental duodenal and gastric ulceration; gastric, pancreatic, and duodenal secretion; gastrointestinal motility; and gastric and intestinal submucosal blood flow regulation. There also is support for the use of dopamine and dopamimetic agents in the treatment of certain experimental gastrointestinal diseases. Some highly selective dopamine agonists are gastroprotective when given either parenterally or centrally. Based on these observations, the authors suggest that dopamine is a key element of the 'brain-gut axis' and represents a potentially important target for pharmacotherapeutic exploration. 89 references. (AA).
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Metoclopramide: A Dopamine Receptor Antagonist Source: American Family Physician. 41(3): 919-924. March 1990. Summary: This article discusses metoclopramide, a dopamine receptor antagonist with unique properties of increasing lower esophageal sphincter pressure and increasing the rate of gastric emptying. These gastrointestinal motility actions are useful in the treatment of diabetic gastroparesis and severe gastroesophageal reflux and in postoperative situations involving visceral atony. The author covers the chemistry, pharmacology, clinical uses, adverse reactions, and drug interactions of metoclopramide. Metoclopramide is a useful adjunctive drug for intestinal intubation and radiologic examination. It has also been used intravenously to control the nausea and vomiting of intensive cancer chemotherapy, such as with cisplatin. Intravenous metoclopramide is generally not intended for long-term use. The most common adverse reactions are restlessness, drowsiness, fatigue, and lassitude. 3 tables. 35 references. (AA-M).
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Effect of Postoperative Low-Dose Dopamine on Renal Function After Elective Major Vascular Surgery Source: Annals of Internal Medicine. 120(9): 744-747. May 1, 1994. Summary: This article reports on a study undertaken to determine the effect on renal function of postoperative low-dose dopamine administered to patients after elective, major vascular abdominal surgery. The randomized, double-blind placebo-controlled trial involved 37 patients undergoing either elective repair of an abdominal aortic aneurysm or aortobifemoral grafting--18 received dopamine, and 19 received placebo. Plasma creatinine levels, urea levels, and creatinine clearance were measured preoperatively and postoperatively (at 24 hours and 5 days). Two postoperative deaths occurred in the dopamine group (from renal failure and myocardial infarction). Four patients had myocardial infarction--three of whom received dopamine. Plasma creatinine levels remained unchanged in both groups. The authors conclude that, within the limitations of the small size of the study, low-dose dopamine appeared to offer no advantage to euvolemic patients after elective abdominal aortic surgery. However, patients with acute oliguric renal failure were not included in the study. 3 tables. 16 references. (AA-M).
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Dopamine Receptor Genetic Variation, Psychosis, and Aggression in Alzheimer Disease Source: Archives of Neurology. 55: 1335-1340. October 1998. Summary: This journal article describes a study that examined whether selected polymorphisms in the dopamine receptor genes DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or aggressive behavior in patients with Alzheimer's disease (AD). Researchers evaluated a cohort of 275 elderly outpatients diagnosed with probable AD for behavioral symptoms and classified them for the presence of psychotic symptoms and physical aggression. Data showed that, among white patients, psychosis and aggression were significantly more frequent in DRD1 B2/B2 homozygotes; psychosis was significantly more frequent in DRD3 1/1 or 2/2 homozygotes. The joint risk for psychosis caused by the DRD1 and DRD3 polymorphisms exceeded the risks caused by either locus alone; this suggests an interaction. Neither the DRD2 S311C polymorphism nor the presence of long alleles for the DRD4 exon III repeat sequence was associated with psychosis or aggression. The authors conclude that genetic variation in DRD1 and DRD3 genes may act to modify the
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course of AD by being predisposed to the development of psychotic or aggressive symptoms. 4 tables, 58 references (AA-M).
Federally Funded Research on Dopamine The U.S. Government supports a variety of research studies relating to dopamine. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to dopamine. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore dopamine. The following is typical of the type of information found when searching the CRISP database for dopamine: •
Project Title: ADENOSINE /DOPAMINE INTERACTIONS IN A2A RECEPTOR KO MICE Principal Investigator & Institution: Chen, Jiang F.; Neurology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-MAY-2004 Summary: (from applicant's abstract): The adenosine A2a receptor (A2aR) is coexpressed with the dopamine D2 receptor (D2R) in striatopallidal neurons and exerts an antagonistic influence on postsynaptic D2R function in brain. Our understanding of A2aR-dopamine interaction, however, is based primarily on pharmacological evidence that is intrinsically limited by the lack of specificity of adenosinergic agents. To elucidate the cellular mechanisms underlying the interaction between A2aRs and the dopaminergic system in vivo, we have generated A2aR knock-out (KO) mice. Our initial characterization of A2aR KO mice reveals a presynaptic role for the A2aR by demonstrating its facilitative effect on striatal dopamine release and, in turn, on dopamine-mediated locomotor activity. Thus, we propose a modified model for the interaction between the A2aR and the dopaminergic system: A2aR-mediated presynaptic facilitation of dopamine release may counterbalance the A2aR-mediated postsynaptic inhibition of D2R function. Hence A2a adenosinergic regulation of dopaminergic activity may depend upon a fine balance between pre- and post-synaptic functions of A2aRs. To pursue this hypothesis, we will study A2aR-dopamine interactions at presynaptic sites using a synaptosomal preparation and in vivo microdialysis (SA #1), and at postsynaptic sites using reserpinized mice and primary cultures of striatal neurons (SA #2). Furthermore, using D2R KO and A2aR-D2R double KO mice we will address the central question whether or not the D2R mediates A2aR functions in vivo (SA #3). We will explore A2aR-dopamine interactions at the behavioral
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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(locomotor activity), neurochemical (dopamine release) and cellular (cAMP formation and c-Fos expression) levels to gain insight into the integrated role of A2aR in vivo. By complementing classical pharmacological studies with these transgenic approaches receptor function, we seek more refined answers to several fundamental questions of adenosine physiology: (1) Do basal levels of endogenous adenosine acting at the A2aR exert tonic physiological effects (inhibitory or excitatory) on the brain dopaminergic system? (2) What are the cellular mechanisms underlying A2aR-dopamine interactions at pre- and post-synaptic sites? (3) Does A2aR specifically require the D2R to exert its neuronal functions in vivo? The answers to these questions will foster the rational development of A2aR agents as an alternative or adjunctive treatment for Parkinson's disease and related disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMPHETAMINE REGULATION OF DOPAMINE TRANSPORT Principal Investigator & Institution: Galli, Aurelio A.; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-JUL-2002 Summary: (provided by applicant): Amphetamine (AMPH) abuse constitutes a significant public health issue with important economic and social ramifications. Treatments are hampered by a lack of knowledge of how AMPH works at the molecular level. The long-term objective of this project is to obtain an understanding of the acute pharmacological modulation of the human dopamine transporter (hDAT) activity by AMPH. Dopamine transporters (DATs) that largely control dopamine (DA) clearance are targets for psychostimulants such as cocaine and AMPH. By acting on the DAT, AMPH attenuates the DAT clearance efficiency. As a consequence, AMPH increases synaptic DA levels and enhances dopaminergic transmission with profound effects on behavior. There has been very little study of the effects of AMPH on DATs at the molecular level. This project will combine molecular biology, biochemistry, confocal microscopy and biophysics to elucidate the mechanisms involved in the acute pharmacological regulation of hDAT function by AMPH. The key issues to resolve include how AMPH causes massive release of DA via bDAT, and how AMPH causes hDAT cell surface redistribution, a novel mechanism recently uncovered by us. Both these processes affect the hDAT-mediated DA reuptake, ultimately increasing the extracellular DA concentration. The experimental plan links mechanistic aspects of the transporter function to the pharmacological properties of AMPH, namely AMPHinduced hDAT currents to AMPH-stimulated DA efflux and AMPH-induced hDAT cell surface redistribution. The proposed studies address the following specific aims: 1) to characterizethe ion, voltage and substrate regulation of the AMPH-induced hDAT currents; 2) to determine the relationship between AMPH-induced hDAT current and AMPH-stimulated DA efflux; and 3) to identify the cellular components involved AMPH-induced trafficking of the hDAT. This proposal seeks to identify molecular mechanisms of the AMPH action and to reveal new cellular targets for substance abuse therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATTENTIONAL PROCESSING OF TEMPORAL INFORMATION Principal Investigator & Institution: Buhusi, Catalin V.; Assistant Professor; Psychology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 04-FEB-2002; Project End 31-JAN-2007
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Summary: (provided by applicant): Fundamental behavioral processes such as associative learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals in the seconds-to-minutes range (interval timing). One of the underlying assumptions of most timing theories is that subjects are able to readily abstract from the input stimulus the temporal information, and to tune their behavior according to this cue, irrespective of non-temporal properties the real timed event. In contrast, evidence suggests that both animal and human timing is highly sensitive to properties of the timed signal thus supporting the notion of an "attentional switch/gate" interval timing mechanism. The objective of this proposal is to study attentional processing of temporal information in the seconds-to-minutes range (interval timing) using a multi-level, behavioral, neuropharmacological, and computational approach. Behaviorally, the investigator will study a newly developed interval timing procedure shown to engage attentional processing of temporal cues. Within this procedure, the investigator proposes to evaluate the impact of the characteristics of stimuli on timing and memory for timing. Pharmacologically, the investigator proposes to dissociate the clock effects and attentional effects of specific dopamine agonists and antagonists on interval timing. We also propose to investigate the neural substrates involved in the attentional switch/gate mechanism of timing. Computationally, the investigator proposes to develop a model of the attentional switch/gate mechanism of interval timing in order to address the effect of behavioral and pharmacological manipulations on attentional processing of temporal information. The studies will inform current models of timing, time perception, and neuropharmacology of interval timing. They will provide new means for understanding the impact of attentional factors on complex cognitive mechanisms that require temporal processing. They will help elucidate the pharmacological and neural basis of attentional processing of temporal information Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASAL GANGLIA NEUROPHYSIOLOGY DURING DBS IN RATS Principal Investigator & Institution: Chang, Jing-Yu; Assistant Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Parkinson's disease (PD) is a degenerative neurological disorder affecting millions of patients all around the world. Renewed use of the deep brain stimulation (DBS) method provides a new opportunity for treating PD. A key issue to improve the treatment is to fully understand the neural mechanisms underlying the therapeutic effects of DBS. In this proposed study, two unique techniques developed in our laboratory: the chronic multiple-channel single unit recording and rat model of DBS, will be employed to study the neural responses in multiple basal ganglia regions during behaviorally effective DBS in rat model of Parkinsonism. A first objective is to establish a rodent model of DBS in Parkinsonian conditions. The effects of DBS will be evaluated in dopamine lesioned rats performing treadmill locomotion and limb use asymmetry tests. Locomotor d deficits during treadmill walking and imbalance usage of forelimb in vertical exploratory behaviors will develop after unilateral dopamine lesion. High frequency stimulation (HFS) of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) will then be applied to alleviate these motor abnormalities. The degree of dopamine depletion in the basal ganglia will be detected by immunohistochemical staining of dopamine marker and this result will be correlated with the severity of motor deficits and DBS effects. Second, the basal ganglia neural responses following a dopamine lesion and during
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behaviorally effective HFS will be examined. Single neural activity and local field potential in the striatum globus pallidus, STN and SNr will be recorded simultaneously in a 64 channel recording system in the rat performing these behavioral tests. Neural responses following dopamine lesion will help us to understand the pathophysiologic process of developing Parkinsonian syndromes while the neural responses during behaviorally effective HFS will shed light on how DBS can restore normal information processing in the basal ganglia neural circuits that are disrupted following dopamine lesion. Several important improvements on recording and stimulation techniques will be made in cooperation with Biographic Inc. to achieve optimal conditions for high frequency stimulation and artifact free recording. The goal of this study is to explore the basic neural mechanism underlying the therapeutic effects of DBS and the knowledge obtained form this study will help us to improve the clinical treatment of PD with DBS method. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL CHARACTERIZATION OF ACUTE&CHRONIC AMPHETAMINE Principal Investigator & Institution: Segal, David S.; Professor; Psychiatry; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 29-JUN-1976; Project End 31-MAY-2006 Summary: Methamphetamine abuse has significantly increased over the past decade and the availability of relatively pure, high potency forms of the drug has led to more chronic, high dose exposure patterns. Converging evidence suggests that profound neurochemical and neuropsychiatric changes can result from methamphetamine abuse and that alterations in striatal dopamine transmission may be implicated in many of these effects. However, it is unclear whether these changes reflect neurodegeneration or adaptational adjustments, nor if functional recovery occurs after discontinuation of drug. Such information is a critical prerequisite to the rational development of effective therapeutic interventions. The proposed research will use a newly developed methamphetamine treatment paradigm that closely simulates, in rats, the drug exposure conditions associated with a high dose, maintenance pattern of methamphetamine abuse, in order to characterize the temporal changes of a broad spectrum of neurochemical and behavioral indices associated with striatal dopamine neuronal transmission. The specific studies are designed to test our hypotheses that: (1) repeated multiple daily administration of methamphetamine will produce profound neurochemical (striatal dopamine nerve terminal markers) and behavioral (spontaneous activity, behavioral organization, and short-term memory) impairments in the absence of dopamine neuronal degeneration; (2) the changes in dopamine transmission (including measures of the dopamine transporter and the vesicular monoamine transporter, as well as extracellular dopamine) and related behavioral deficits will exhibit complete recovery over time; (3) during the late stages of methamphetamine treatment, a spectrum of behaviors associated with the development of paranoid psychosis in stimulant abusers (hyperarousal, increased aggressivity and responsiveness to stress) will gradually emerge, corresponding to a shift in the relative caudateputamen and nucleus accumbens dopamine responses; and, (4) both the altered behavioral and dopamine effects in response to acute methamphetamine challenge will exhibit gradual recovery over time after discontinuation of chronic treatment. The results of these studies should provide greater insight into the mechanisms and processes contributing to the behavioral and neurochemical consequences associated with a common pattern of methamphetamine abuse.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL EFFECTS AND ABUSE OF DOPAMINERGIC DRUGS Principal Investigator & Institution: Bergman, Jack; Associate Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2003; Project Start 01-AUG-1985; Project End 31-JAN-2008 Summary: (provided by applicant): The abuse and addictive power of psychomotor stimulants such as methamphetamine and cocaine continue to be a critical national concern. Much evidence has pointed to the interplay of dopaminergic and nondopaminergic mechanisms in the effects of these drugs; however, mechanisticallybased medications are not yet available. Research is proposed along two lines to address this continuing lack of anti-stimulant therapeutics. The first, based on the use of the partial agonist buprenorphine for the management of opioid addiction, pertains to the analogous development of dopamine partial agonists for stimulant addiction. A goal of the present research is to examine the potential value of dopamine partial agonists by examining their anti-stimulant effects in monkeys. This will be done using a novel selfadministration choice procedure: in this procedure, subjects learn to distribute their behavior on the basis of the relative reinforcing strengths of an i.v. solution that is available for self-injection and an alternative reinforcer (food). This procedure is especially designed to divorce the reinforcing strength of drugs from their other behavioral effects. Partial agonists at different subtypes of dopamine receptors will be studied for their ability to specifically counter the reinforcing strength of methamphetamine and cocaine. A second line of research is based on the need for a firm grasp of the role of nondopaminergic mechanisms in the behavioral effects of psychomotor stimulants, especially in primate species. In acute studies, psychomotor stimulants will be studied by analyzing the cholinergic and noradrenergic mechanisms that complement dopamine activity in preclinical assays of abuse liability, in chronic studies with different types of dopaminergic drugs, behavioral assays and in vitro autoradiography will be used to describe changes in monoamine transporter and receptor densities that may accompany alterations in pharmacological sensitivity. Overall, this program will strengthen our fundamental understanding of dopaminemediated behavioral effects of methamphetamine and other psychomotor stimulant drugs. This research should point to novel directions for the development of medications with which to manage the abuse and addictive liabilities of psychomotor stimulant drugs Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BEHAVIORAL GENETICS OF IMPULSIVITY Principal Investigator & Institution: Fairbanks, Lynn A.; Associate Professor; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): Impulsivity is a common feature of numerous psychological, psychiatric and social problems, including conduct disorder, attention deficit hyperactivity disorder, substance abuse, antisocial personality disorder, criminality and violence. Behavioral genetics studies have consistently demonstrated significant genetic contributions to individual differences in personality traits and behavioral outcomes related to impulsivity, and there is increasing evidence that impulsivity and impulsive aggression may be mediated, in part, by activity of the
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monoaminergic (serotonin, dopamine and norepinephrine) neurotransmitter systems. However, little is known about the genetic covariance between behavioral and neurobiological phenotypes, or the role of specific environmental influences in the development of impulsivity within a complex natural social system. Proposed here is a longitudinal study that follows related individuals from infancy to adulthood, collects objective, prospective measures of environmental variables and behavioral phenotypes, and concurrently assesses neurobiological variables in a nonhuman primate model appropriate for quantitative behavioral genetics analysis. Subjects for this research are 725 vervet monkeys (Cercopithecus aethiops sabaeus), living in naturally composed social groups in a multigenerational, pedigreed colony that includes full siblings, maternal and paternal half siblings, and dyads of varying degrees of relatedness. The objectives of this investigation are to a) assess the relative contribution of genetic and environmental factors to variation in impulsivity at different life stages, b) to determine the contribution of specific early experiences (maternal style, family social status, peer relationships) to variation in impulsivity, and c) to evaluate the role of monoaminergic neurotransmitter systems in mediating genetic influences on impulsivity. To accomplish these objectives we propose to 1) measure individual differences in impulsivity in standardized situations from one year of age to adulthood, 2) collect objective, prospective data on individual experiences during development, 3) assess longitudinal variation in metabolites of serotonin, dopamine and norepinephrine in cerebrospinal fluid, and 4) identify genetic polymorphisms at loci in serotonergic and dopaminergic pathways (serotonin transporter, tryptophan hydroxylase, dopamine transporter and dopamine receptor DRD4 genes) for use in candidate gene linkage analysis. The proposed research will provide new information on the genetic, environmental and neurobiological contributions to development of individual differences in a dimension of temperament that is a major risk factor for behavioral, psychological and psychiatric problems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN DOPAMINE ALTERATIONS IN HUMAN COCAINE USERS Principal Investigator & Institution: Little, Karley Yates.; Associate Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY-2007 Summary: (provided by applicant): Brain dopamine neurons appear to be injured by chronic cocaine exposure in human users. Striatal VMAT2 binding sites, VMAT2 IR, and dopamine concentrations, as well as midbrain melanized neurons and DAT mRNA are decreased in post mortem human samples that we have examined. Cocaine-related neurotoxicity in humans could contribute to disordered reward experience, and specific symptoms such as craving and depression. Goal #1 is to confirm that dopamine neurons are lost in midbrain, paralleled by loss of striatal dopaminergic fibers, in human cocaine users. Specific Aim #1 is to test the hypotheses that dopamine neurons are lost in the anterior dorsal tier of pars compacta of human cocaine users. Dopamine cell numbers will be quantitated in major dopamine nuclei at four AP levels in available specimens, using stereological methods and naturally occurring melanin inclusions and tyrosine hydroxylase (TH) immunohistochemical staining to identify dopamine cells. GABA neurons will be evaluated to assess the specificity of the cocaine effect. VMAT2 decreases could result from cocaine-induced regulation of VMAT2 protein, or neurotransmitter vesicles. Goal #2 is to clarify if human cocaine users experience dopamine-specific regulation of neurotransmitter vesicle levels. Specific Aim #2 is to
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test the hypotheses that the vesicle-associated protein, synaptotagmin 1, decreases, while the synapse-associated protein, syntaxin, does not, specifically in dopamine neurons. VMAT2, syntaxin, and synaptotagmin 1 mRNA levels will be quantitated in midbrain regions, while further characterization of synaptotagmin subtypes and other synaptic protein levels will be assessed in striatum. Dopamine neurons have specific, topographically organized projections that subserve distinct motor versus limbic functions. Goal #3 is to better understand the anatomical extent that dopamine function is affected in cocaine users and to determine if regional pattems exist in stdatum. Distinct among dopamine markers, striatal dopamine transporter (DAT) function is increased, and could be related to the toxic effects of long-term cocaine exposure. Specific Aim #3 will test the hypothesis that cocaine users display both decreased striatal VMAT2 binding sites and increased DAT binding in a co-varying pattern that is most intense in anterior ventromedial striatum. DATNMAT2 expression in amygdalar nuclei subserving reward/emotional functions will also be examined. Methamphetamine toxicity in mice appears to involve excessive sodium influx into dopamine neurons, inducing increases in energetic (COX-l) and sodium exchange (NHE-1) enzymes, which were both increased in six cocaine users. Goal #4 is to confirm these increases and determine if induction of related genes occurs in human cocaine users. Specific Aim # 4 is to test the hypotheses that COX-l, NHE-1 and related mRNA's are increased in dopamine neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN DOPAMINE FUNCTION IN ADULTS WITH ADHD Principal Investigator & Institution: Wang, Gene-Jack; Brookhaven Science AssocBrookhaven Lab Brookhaven National Lab Upton, Ny 11973 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Attention-deficit hyperactivity disorder (ADHD) is the most frequent psychiatric disease in children affecting about 3 million children in the USA. Yet we know very little about the pathophysiology of the disease or of the effects of chronic treatment with psychostimulant drugs (which have been used for ADHD for more than 40 years) in the human brain. This places a sense of urgency on identifying the neurochemical changes occurring in ADHD and their response to treatment. There is mounting evidence that brain dopamine (DA) dysfunction is involved in ADHD and that psychostimulant-induced elevations in brain DA are involved in its treatment. Here we hypothesize that ADHD subjects have a deficit in DA cell function, which results in too little extracellular DA and leads to synaptic adaptations (decreases in DA transporters (DAT) that remove synaptic DA) to compensate for this deficit. We also postulate that while acute treatment temporarily compensates for this deficit, chronic treatment could further exacerbate the DA changes. We propose to test these hypotheses in never-medicated adults with ADHD. We will use positron emission tomography (PET) to measure DAT using [11C]cocaine (DAT radioligand) and to assess DA cell function using the dopamine D2 receptor radioligand [11C]raclopride with and without a challenge dose of methylphenidate (drug that increases DA by blocking DAT). We propose to test ADHD subjects (n = 35) at baseline and after 12-14 months treatment with psychostimulant medication. Normal controls (n = 35) will be similarly evaluated and will be retested 12-14 months later to assess reproducibility. The working hypotheses for this proposal are: (1) Never-medicated ADHD subjects will have lower than normal function of DA cells (seen as decreased extracellular DA) and a compensatory reduction in DAT. (2) Chronic treatment of ADHD subjects with psychostimulant medication, which increase extracellular DA, will result in an increase
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of DAT and reductions in extracellular DA (when tested off medication). Despite the high prevalence of ADHD and its multiplicity of adverse consequence, the diagnosis of ADHD has remained controversial. This controversy is driven by a lack of understanding of the biological basis of the disorder and the fact that the most frequently used medications in the treatment of ADHD (methylphenidate and amphetamine), have reinforcing effects and can be diverted for drug abuse. After a halfcentury of clinical recognition and treatment of ADHD, a better understanding of the neurochemistry underlying this disease and the potential effects that chronic stimulant treatment may have on the human brain is long overdue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CALCIUM SIGNALING IN REWARD CIRCUIT AND DRUG ADDICTION Principal Investigator & Institution: Morikawa, Hitoshi; Waggoner Center for Alcohol and Addiction Research; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Dopaminergic neurons in the ventral midbrain, i.e., the ventral tegmental area and the substantia nigra pars compacta, are believed to be critically involved in the perception of reward and addiction to drugs of abuse, such as psychostimulants and opioids. The firing pattern of dopamine neurons, which is controlled by excitatory and inhibitory synaptic inputs, is significantly modulated by presentation of rewards and administration of drugs of abuse. Modulation of dopamine neuron firing affects dopamine release in target structures, and hence contributes to reward-driven motivated behaviors in vivo, including drug-seeking and drug-taking behaviors. It has been shown recently that repetitive stimulation of glutamatergic inputs to dopamine neurons evokes a slow inhibitory postsynaptic potential mediated by activation of metabotropic glutamate receptors (mGluRs). This hyperpolarization results from the opening of calcium-activated potassium channels following release of calcium from intracellular stores. The overall hypothesis of the proposal is that this calciummediated inhibition plays a key role in controlling the excitability of dopamine neurons and in psychostimulant-induced modulation of dopamine neuronal activity. The first aim is to determine the intracellular signaling pathway mediating the release of calcium following the activation of mGluRs. This will be accomplished by combined whole-cell patch clamp recording and confocal calcium imaging techniques using acutely prepared midbrain slices from rats. Furthermore, flash photolysis of caged compounds will be performed to examine the effects of second messengers applied directly into the cytosol on a millisecond time scale. These methods will enable detailed examination of the intracellular events that follow the activation of plasma membrane receptors. The second aim is to determine the impact of this glutamate-induced hyperpolarization on the firing pattern of dopamine neurons. An effort will be made to reproduce the firing pattern observed in vivo in an in vitro slice preparation. The third aim is to investigate how acute administration of psychostimulants interferes with the mGluR-induced inhibition to modulate the firing pattern of dopamine neurons. The information obtained will open a new avenue toward the understanding of the neural mechanism responsible for the development of drug addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CART AND THE DOPAMINE SYSTEM IN THE NUCLEUS ACCUMBENS Principal Investigator & Institution: Hunter, Richard G.; Pharmacology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-OCT-2002; Project End 31-JUL-2004 Summary: (provided by applicant): CART (cocaine- amphetamine-regulated transcript) was discovered as an mRNA up-regulated in ventral striatum after acute cocaine and amphetamine. Further studies have shown the peptide and mRNA are expressed at high levels in the projection neurons of the nucleus accumbens (NA), particularly in the shell. Furthermore these neurons appear to receive input from dopamine terminals originating in the VTA. Increases in locomotion result from intra-VTA injection of CART peptide, an effect which is blocked by haloperidol. These data suggest a relationship between CART neurons in the NA and the mesolimbic dopamine system. No CART receptor is yet known. The aim of this study is to test the hypothesis that CART and the dopamine (DA) system interact in the NA. Using double in situ hybridization, it will be determined if CART co-localizes with dopamine receptors in cells of the NA. To examine if DA regulates CART, CART mRNA and peptide will be measured. The interaction will be tested using 6-OHDA lesions, and local and systemic injection of dopamine receptor selective agonists and antagonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CENTER FOR GENE-ENVIRONMENT STUDIES IN PARKINSON DISEASE Principal Investigator & Institution: Chesselet, Marie-Francoise S.; Charles H. Markham Professor of Neurolog; Brain Research Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 26-AUG-2002; Project End 31-JUL-2007 Summary: The Center for Gene-Environment studies in Parkinson disease at UCLA (UCLA-CGEP) will bridge three major NIH and VA-supported awards in Parkinson's disease (PD) and one NIH-sponsored study of Huntington's disease. The central hypothesis of the proposed UCLA-CGEP is that gene and environmental toxins combine to increase the risk for PD in susceptible individuals through an interplay between pesticides and mechanisms regulating dopamine homeostasis. We postulate that critical factors in this interaction are oxidative stress and resulting alterations in proteasomal function. Project I "Environmental toxins and genes that influence dopamine in Drosophila and humans" will examine interindividual variability of dopamine vesicular transporter (VMAT) expression due to promoter variants in two human populations in parallel with a reporter gene assay. These populations will be genotyped for functional VMAT2 variants and association analyses of gene-environment interactions and pesticide exposures collected in the parent grant will be conducted. In addition, Drosophila genetics will be used to determine how the expression of VMAT affects dopamine-mediated toxicity and identify genes that modulate VMAT function, which will then be examined in the human population for their relevance to increased risk of PD. Project II "Interaction between pesticides and genetic alterations in dopamine homeostasis in mice" will test the hypothesis that pesticides and genetic variations in combination increase the vulnerability of dopaminergic neurons, and that one of the mechanisms involved is oxidative stress. Genetically engineered mice with a reduction in expression of VMAT or the cytoplasmic dopamine transporters, and mice with altered expression of alpha-synuclein and parkin, two proteins known to cause familial
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PD, will be examined. Behavior and quantitative anatomy will be used to assess the effect of pesticides on dopaminergic neurons in these genetically altered mice. Histology, gene expression profiling, in vivo neurochemistry and slice electrophysiology will be used to examine the role of oxidative stress in this interaction. Project III, "Pesticides and Proteasomal Dysfunction: genetic susceptibility in cellular models" will test the hypothesis that proteasomal dysfunction is central to the deleterious effects of the combined environmental and genetic insults. Cell lines, primary neuronal cultures from genetically altered mice, and human lymphoblasts will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE INDUCED OPIOID, DOPAMINE AND BEHAVIORAL CHANGES Principal Investigator & Institution: Unterwald, Ellen M.; Associate Professor; Pharmacology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAR-2003 Summary: APPLICANT'S ABSTRACT: The goal of the proposed research is to identify neurochemical alterations that occur during in vivo exposure to cocaine and to elucidate their functional significance. The identification of neurobiological imbalances that occur due to prolonged exposure to cocaine is critical for understanding the long-term consequences of cocaine abuse and for developing effective pharmacological treatment strategies. In previous studies, cocaine was administered to rats in three daily injections given at one-hour intervals for 14 days to mimic the binge-pattern of administration that often occurs in human cocaine abusers. Results demonstrate that mu and kappa opioid receptors and Dl dopamine receptors are upregulated in several brain regions of rats treated chronically with cocaine. In addition, the ability of delta opioid receptor agonists to inhibit adenylyl cyclase activity is attenuated, suggesting a functional uncoupling of delta opioid receptors and G-proteins. These finding are the basis of the proposed research, with the following specific aims. Studies will be performed to determine the impact of dosing regimen on the neurochemical alterations produced by cocaine. The effect of cocaine administered by several paradigms that produce either behavioral sensitization or tolerance on opioid receptors, dopamine receptors, and dopamine transporter sites will be determined. To investigate the functional consequences of cocaine-induced receptor alterations, the ability of opioid and dopamine receptor agonists to regulate adenylyl cyclase activity will be determined in brain regions of control and cocaine treated rats. Adenylyl cyclase activity will be assessed by measuring the accumulation of cAMP in the nucleus accumbens, caudate putamen, and olfactory tubercle. Cocaine-induced changes in opioid receptor binding and opioid receptorregulated adenylyl cyclase activity may be due to changes in the coupling of opioid receptors and G-proteins. The state of opioid receptor coupling will be investigated by determining the sensitivity of opioid agonist binding to guanine nucleotides and by comparing the affinities of opioid agonists and antagonists in brain sections from control and cocaine-treated animals. Receptor/G protein coupling will be assessed in several specific brain regions by performing these assays on tissue sections and generating autoradiograms. Finally, the regulation of opioid receptors dopamine receptors, and adenylyl cyclase activity during cocaine administration will be determined in murine models. Studies in mice will establish that the neurochemical perturbations caused by cocaine administration are relevant across species, and, hence, may be more generalizable to human cocaine abuse. In addition, the mechanism of cocaine's actions on opioid and dopamine systems will be investigated by studying this regulation in transgenic mice, in mice with targeted gene deletions (gene knock-outs), and in mice
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with a particular genetic trait such as a genetic preference for cocaine, morphine, and ethanol. For example, the role of Dl receptors in cocaine-induced opioid receptor regulation will be investigated by determining the effects of cocaine on opioid receptor expression in mice that are devoid of Dl receptors. Collectively, these studies will identify the neurochemical perturbations that occur during chronic cocaine exposure and identify the cellular and molecular mechanisms of this regulation. The potential outcome of these studies may be the information necessary for the development of more selective pharmacotherapeutic agents for the chronic management of cocaine addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE-BINDING DOPAMINE TRANSPORTER: MOLECULAR BIOLOGY Principal Investigator & Institution: Bannon, Michael J.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-APR-1990; Project End 31-JAN-2008 Summary: (provided by applicant): Neurons utilizing dopamine (DA) as a neurotransmitter constitute a rare neurochemical phenotype but nevertheless play an important role in regulating locomotion, motivation, cognition and hormone release. The DA transporter (DAT) is a plasma membrane transport protein that controls the spatio-temporal domains of DA neurotransmission by rapidly reaccumulating DA that has been released into the extracellular space. A wide spectrum of neurological and psychiatric disorders, including drug abuse, Parkinson's disease, schizophrenia, affective disorders, and attention deficit hyperactivity disorder is thought to involve DA systems and the DAT. The DAT is an important target for therapeutic and illicit drugs (e.g. methylphenidate, buproprion, amphetamine, and cocaine), and serves as the point of entry for DA-specific neurotoxins. DAT radioligand binding provides an in vivo measure of DA cell integrity and can be used to monitor the efficacy of therapeutic interventions in neurodegenerative disease. The Aims of this project are to identify the silencing element(s) and cognate transcription factor(s) that repress transcription of the human dopamine transporter gene in non-dopaminergic cells, as well the mechanism by which the transcription factor nurrl activates human dopamine transporter gene transcription in dopamine neurons. It is likely that a greater understanding of the regulation of the DAT expression will impact the diagnosis and treatment of a number of neuropsychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF COGNITIVE FUNCTIONS: FRONTAL LOBE Principal Investigator & Institution: Diamond, Adele D.; Professor, Department of Psychiatry; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 10-JUN-1997; Project End 31-MAY-2004 Summary: The goals of the proposed research are three:(1) to test children with brain damage localized to frontal cortex on tests (a) which have been linked specifically to frontal cortex function through neuroanatomical and behavioral studies with infant and adult monkeys and (b) on which we know the normal developmental progression in children. Important aspects of this work will be to look for converging evidence from diverse tests all linked to the same subregion of frontal cortex, and to attempt to dissociate performance on these tests from performance on tests linked to other neural circuits. The goal is to develop non-invasive tests capable of detecting frontal cortex
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damage in infants and young children. Presently such damage often goes undetected for many years because of the lack of such tests. (2) to investigate the relationship of dopamine levels to performance on these tasks, and to begin to investigate the hypothesis that the fundamental maturational change which underlies the emergence of cognitive abilities dependent on frontal cortex during infancy is increasing levels of frontal cortex dopamine. To do this, children with early-treated PKU, who have no known structural brain damage but who are vulnerable to reduced levels of dopamine will be tested. Because their general cognitive functioning is good, if deficits are found they are likely to be selective. If they are selectively impaired on tests of frontal cortex function, this will be the first demonstration in humans of a cognitive deficit on frontal cortex tasks from dopamine depletion alone. Because L-dopa and the dopamine precursor, tyrosine, can be taken orally, there is an excellent chance that if deficits are found, therapeutic interventions will be possible to alleviate any impairments. (3) to better understand the abilities required for success on tasks that depend on frontal cortex function. Hypotheses will be considered that suggest that memory for space, and/or time, or for relational information in general is dissociable from memory for other information and dependent upon frontal cortex function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF POTENTIALLY SELECTIVE DOPAMINE AGONISTS Principal Investigator & Institution: Nichols, David E.; Professor; Medicinal Chem/Molecular Pharm; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 31-MAR-2006 Summary: (provided by applicant): This application requests continued support of our drug design efforts aimed both at novel ligands that are dopamine receptor (DAR) isoform-selective agonists, and that can be used as tools to probe the structure and function of this subfamily of GPCRs. Although we are one of the few academic laboratories in the world actively pursuing these lines of research, this project has had a long and successful history in the design and synthesis of dopamine D1/D5 agonists, and their use in understanding DAR function. The design and synthesis efforts supported by this work occur in the context of an independently funded long-term collaboration that provides important pharmacological and computational input. One direction to be pursued is synthesis and characterization of new molecules that will permit the development of a body of data that would lead to the design of agonists selective for the D5, the D1, or both isoforms. These are classes of drugs that do not currently exist, but for which there would be exquisite research and even clinical utility. Full efficacy dopamine D1/D5 agonists are starting to be recognized for their potential as the most effective therapeutic agents for the treatment of mid- and late stage Parkinson's disease, and there is now good evidence that such agonists may also be useful in treating cognitive deficits induced by certain neuroleptics, improving memory, in reversing the negative symptoms of schizophrenia, etc. The approach to be employed is driven by medicinal chemistry and proposes the synthesis of structural modifications that focus on the B-phenyl-B-dopamine pharmacophore that we have identified and used as a template with outstanding success. We have produced three structurally diverse dopamine agonists from this template, and all of them have shown remarkable efficacy vs MPTP-parkinsonism in nonhuman primates. This work provides a foundation for molecular exploitation that will lead to additional important compounds. These will define structure-activity relationships that will help to define the nature of
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the binding domains necessary to activate the target dopamine receptors. We shall also follow-up on substantial improvements in pharmacokinetic properties we have made without sacrificing desired pharmacodynamic characteristics. The products of this work have a high likelihood of significant impact on basic studies of receptor function, and on the therapy of numerous CNS disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL NEURODEGENERATION
PESTICIDE
EXPOSURE
AND
Principal Investigator & Institution: Miller, Gary W.; Associate Professor; Environmtl/Occupatnl Hlth Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Developmental Organochlorine Exposure and Neurodegeneration Parkinson's disease (PD) is characterized by the selective death of nigrostriatal dopamine neurons. The resultant loss of dopamine input to the striatum leads to hallmark motor symptoms of the disease. Epidemiological studies have revealed pesticide exposure as a risk factor for PD and post-mortem studies have demonstrated that organochlorine insecticides are elevated in PD brains. Our lab has previously shown that exposure of adult mice to organochlorine insecticides alters the expression and function of the dopamine transporter (DAT), a key regulator of dopamine neurotransmission and a gateway for dopaminergic toxins. We now have evidence that exposure to these compounds during development increases DAT expression in young mice. The purpose of this study is to examine the effects of organochlorine insecticides on the development of the nigrostriatal dopamine system and to determine if such exposures predispose the animals to parkinsonism. Specific Aim 1. Gestational and lactational exposure to organochlorine insecticides disrupts the development of the nigrostriatal dopaminergic system. In this aim, we will test the hypothesis that developmental exposure to organochlorine insecticides disrupts nigrostriatal dopamine system gene expression in young and adult mice. Real-time PCR, laser capture microdissection, behavioral testing, neurochemistry, and immunochemistry will be performed to determine the effects of the insecticides on the dopamine system. Specific Aim 2. Gestational and lactational exposure to organochlorine insecticides increases susceptibility of dopamine neurons to MPTP. This aim will test the hypothesis that permanent alterations in the expression of key components of dopaminergic neurons by developmental exposure to organochlorines renders these animals more susceptible to the parkinsonism-inducing toxin MPTP. After developmental exposure to insecticides, adult mice will be exposed to MPTP and analyzed as in Aim 1. Completion of these specific aims will provide crucial information regarding the effects of developmental exposure of pesticides on the integrity and vulnerability of the nigrostriatal dopamine system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL ANTIPSYCHOTICS
PSYCHOPHARMACOLOGY
OF
Principal Investigator & Institution: Wiley, Jenny L.; Associate Professor; Pharmacology and Toxicology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008
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Summary: (provided by applicant): Antipsychotics are administered to children and adolescents for a number of disorders with chronic use often continuing into adulthood. Yet, little is known about short- and long-term effects of these agents on the developing brain and behavior. Research on the effects of atypical antipsychotics (e.g., clozapine) that do not produce extrapyramidal motor effects is particularly lacking. The major hypotheses of this grant proposal are that (1) developing animals are more sensitive to the effects of dopamine antagonists, including antipsychotics, on motor processes than are adult animals and (2) chronic dosing with antipsychotics during development produces long-term changes in response to challenges with dopaminergic agents in later life such that animals are more sensitive to the effects of dopamine agonists and less sensitive to those of dopamine antagonists. In order to test the first hypothesis, rats of different ages (postnatal day 22 to adult) will be administered acute doses of selected antipsychotics; subsequently, they will be evaluated in behavioral procedures designed to measure motor activity (locomotion and catalepsy). In order to test the second hypothesis, rats will be chronically injected with selected antipsychotics during development. After reaching adulthood, these rats will be evaluated in behavioral procedures to evaluate motor activity (locomotion and catalepsy), cognition (sensorimotor gating, acquisition of a response, short-term memory), and the reinforcing efficacy of food. In addition to baseline activity in these procedures, the effects of challenges with antipsychotics and dopamine agonists will also be assessed in these rats. In order to determine possible underlying changes in dopamine receptor binding and distribution, autoradiography of the brains of rats that received identical chronic injection regimens will be performed using radioligands selective for dopamine D1 and D2 receptors. The proposed studies will provide empirical information on acute and long-term effects of traditional and atypical antipsychotics on the developing brain and behavior. This information will help to provide a more rational basis for making treatment decisions concerning children and adolescents who may benefit from treatment with an antipsychotic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE & ACH REGULATION OF INHIBITION IN PFC Principal Investigator & Institution: Seamans, Jeremy K.; Professor; Physiology and Neuroscience; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 07-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): The prefrontal cortex (PFC) is involved in the ability to use previously acquired information to guide forthcoming action, termed working memory. The cellular processes underlying working memory are regulated by both inhibitory neurons and dopamine (DA). Dysfunction of inhibitory and DA systems in the PFC is also thought to underlie aspects of schizophrenia, yet the manner in which these systems interact, is relatively unknown. The main goal of the proposed research is to study the mechanisms of dopamine (DA) modulation of inhibition in the prefrontal cortex (PFC). Preliminary data showed that dopamine has temporally biphasic effects on inhibitory postsynaptic potentials (IPSCs) onto pyramidal neurons in the PFC, producing an initial D2-mediated reduction in IPSC amplitude, followed some minutes later by a D1- mediated increase in IPSC amplitude. Based on preliminary data it was hypothesized that the D1 mediated increase in IPSCs was due to increased excitability of interneurons and their axons. Proposed experiments will test this hypothesis by investigating the direct effect of D1 agonists on ionic currents in subtypes of interneurons as well as potential D1 receptor effects on synaptic inputs to interneurons
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in PFC brain slices. In addition, we will test whether the signaling cascades mediating the D1 effects involve adenylate cyclase and protein kinase A, as in other brain regions, by using selective agents which either inhibit or activate these molecules. Preliminary data also showed an interesting interaction between acetylcholine (Ach) and D2 receptors. Specifically, Ach muscarinic antagonists eliminated the D2-mediated reduction in IPSCs while muscarinic agonists mimicked the D2 effect. Based on these data, it was hypothesized that D2 receptors released Ach that acted through muscarinic receptors to reduce GABA release. A number of experiments will test aspects of this hypothesis, including, depletion of vesicular Ach and lesions of the Ach terminals in the PFC, in order to eliminate Ach release and thus D2 mediated effects on IPSCs. These studies will provide a more comprehensive understanding of DA regulation in inhibition in the PFC, and how it might regulate cellular processes involved in working memory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE AND OXIDATIVE STRESS IN PARKINSON'S DISEASE. Principal Investigator & Institution: Sidhu, Anita; Associate Professor; Pediatrics; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2007 Summary: (provided by applicant): Oxidative stress is an important causative factor in the onset and maintenance of several neurodegenerative conditions, such as Alzheimer's disease and Parkinson's Disease (PD). While dopamine (DA)-replacement therapy can control the symptoms of PD, it can also cause severe dyskinesia in patients. Blockage of the D1 DA receptors with Dl-selective antagonists in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-lesioned primates, significantly improves dyskinesia, through unknown mechanisms. Autoxidation of DA is a major source of free radicals; activation of D1 receptors also triggers oxidative stress, and these effects are additive, such that the resulting damage produced in the postsynaptic cell is several fold greater than that elicited by sources of free radicals (hydrogen peroxide (H202)), which does not stimulate the D1 receptor. Several indices of oxidative stress, lipid peroxidation, nitrite production, nitric oxide synthases, neurofilament (NF)-kappaB nuclear translocation, are all elevated two to six fold higher with DA-mediated D1 receptor activation, than H202 alone. We will examine in detail the contribution of D1 receptor stimulation, through the use of agonists and antagonists, in causing oxidative stress in SK-N-MC human neuroblastoma cells, which endogenously express the D1 receptor and is representative of postsynaptic cells. We will examine the mechanism and functional consequences of D1 receptor stimulation on signaling pathways, as well as by selectively blocking parts of the oxidative stress cascade(s). The participation of D1 receptors and oxidative stress in cell death and apoptosis will also be measured. Since blockage of D1 receptors in the MPTP model of PD improves some of the symptoms of PD, we will investigate whether D1 receptors augment MPTP effects in SK-N-MC cells. Conversely, blockage of D1 receptors with antagonists may attenuate MPTP effects on the various indices of oxidative stress. A clear understanding of the effects of dopamine autoxidation and the participation of D1 DA receptors in inducing oxidative stress, is important for understanding patient response to agonist therapy in PD, and may aid in the design of novel therapeutic treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE AND RETINAL ADAPTATION Principal Investigator & Institution: Witkovsky, Paul; Professor; Ophthalmology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2000; Project Start 01-APR-1980; Project End 31-MAR-2005 Summary: (Adapted from applicant's abstract): The main emphasis of the proposed research is to investigate the cellular and synaptic mechanisms underlying the processes of light and dark adaptation. The major tenet is that the hard wiring anatomically defines the physical synapses, but synaptic efficacy is modified by neuromodulators, such as dopamine, to accommodate the shift from rod- to cone-vision during dark and light adaptation. Studies are proposed to examine the dependency of light, voltage, Ca2+ and dopamine (D2 receptors) on glutamate release by photoreceptors in a "reduced" retina preparation consisting of mostly photoreceptors, and by photoreceptorderived synaptosomes. The effects of dopamine (D2) ligands on rod-cone coupling, as well as rod photovoltage and its flicker response will be examined with intracellular recordings and dye-coupling experiments. In addition, the kinetics of horizontal cell responses and coupling in the horizontal cell network will be studied during light/dark adaptation and during pharmacological manipulations. Recordings from isolated horizontal cells will be used to examine the modulatory effects of amino acid neurotransmitters on time- and voltage-dependent channels, and to assess the contribution each channel makes to sinusoidal modulation of the horizontal cell voltage within the physiological range. The role horizontal cells play in center-surround organization of ganglion cells and the variation of the surround strength as a consequence of light and dark adaptation will also be studied by passing current into horizontal cells while recording extracellular ganglion cell activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE D4 RECEPTOR IN SUSTAINED ATTENTION Principal Investigator & Institution: Zhang, Kehong; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of attention, hyperactivity and excessive impulsive behavior. Although the cause of this syndrome is unknown, genetic factors contribute strongly to its etiology. Recent advances in molecular biology have revealed that such a genetic component is based partially upon the polymorphism of the dopamine D4 receptor gene (DRD4). Using juvenile rats with neonatal dopaminergic lesions, a widely utilized animal model of ADHD, we recently found motor hyperactivity in this model is dosedependently reversed by several D4 receptor-selective antagonists and exacerbated by a D4 agonist. We also found the severity of lesion-induced hyperactivity is significantly correlated to the changes of D4 receptor binding in the basal forebrain. These findings represent rare evidence of a physiological function of D4 receptor, and provide first experimental basis for a specific role of this receptor in ADHD. Recent clinical studies suggest that DRD4 polymorphism is associated with the predominantly inattentive type ADHD as well as attention problems in general population. The importance of D4 receptor in attention is also indicated by converging evidence from biochemical and pharmacological studies in animals. Thus, increased dopamine neurotransmission in frontal cortex, a brain area critical for cognitive function, has been correlated to better performance in an attentional task in rats. Such an increase in dopamine transmission can be produced by D4 antagonists. Accordingly, we propose to study the role of D4
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receptor in sustained attention using a five-choice serial reaction time task (5-CSRTT). Effects of D4 antagonists will be examined in normal rats versus rats screened for poor performance, a putative model for ADHD. Results from the proposed study shall clarify the role of D4 receptor in normal attention process, as well as under conditions that correspond to clinical ADHD. The findings may also provide a pharmacological basis for innovative treatment for ADHD to replace stimulant therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE FUNCTION AFTER PRENATAL ETHANOL EXPOSURE Principal Investigator & Institution: Shen, Roh-Yu; Senior Research Scientist; None; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Our previous studies demonstrate that prenatal ethanol exposure produces a persistent reduction in the electrical activity of midbrain dopamine neurons and alters dopamine receptor sensitivity. These changes are normalized by DA agonist administration. Midbrain DA neurotransmission is involved in many important CNS functions including reward, motor control attention, and locomotor activity. Therefore, prenatal ethanol exposure-induced dopamine hypofunction may contribute to the attention/hyperactivity problems commonly observed in children with fetal alcohol effects, fetal alcohol syndrome (FAE/FAS). In the proposed studies, we will use extracellular and intracellular electrophysiological recording techniques to further characterize the postnatal developmental process of dopamine systems that prenatal ethanol exposure. We will study how these changes may be normalized by dopamine agonists. We will also initiate behavioral experiments to correlate dopamine hypofunction and attention problems. In addition, the cellular leading to a reduction in the electrical activity of dopamine neurons after prenatal ethanol exposure will be examined. The results of these studies will better our understanding in the etiology of behavioral symptoms in FAE/FAS and help us to develop more appropriate animal models to advance the pharmacological treatment of FAE/FAS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE PARTIAL AGONISTS AND PSYCHOSTIMULANT DEPENDENCE Principal Investigator & Institution: Koob, George F.; Director; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 15-AUG-1997; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract) This proposal seeks to extend the focus of investigation conducted during the previous funding period, which was concerned with the effects of dopamine D2 partial agonists on multiple measures of cocaine self-administration and withdrawal, to study the neuropharmacology of methamphetamine dependence. Work during the previous funding period has allowed the characterization of the effects of dopamine D2 partial agonists on both cocaine and amphetamine self-administration under conditions of limited daily access and across full dose effect functions. In addition, the addictive liability of partial agonists has been examined showing that terguride, a prototype dopamine D2 partial agonist, does not function as a substrate for self-administration and does not act as a priming agent reinstating extinguished self-administration. Furthermore, initial studies have addressed the hypothesis that partial dopamine agonists may also act as candidates for pharmacotherapy for amphetamine and methamphetamine dependence. The aim of the
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Dopamine
proposed studies is to further characterize the effects of partial dopamine agonists acting on D1, D2 and D3 dopamine receptor subtypes on methamphetamine dependence. For this purpose, a variety of animal tests tailored to model several components of the methamphetamine dependence cycle will be employed. The guiding hypothesis of the present proposal is that dopamine partial agonists may provide innovative pharmacological measures of interaction with multiple aspects of methamphetamine-seeking behavior that may ultimately lead to the loss of control which represents the cardinal feature of the psychostimulant addictive cycle. A detailed characterization of the effects of dopamine partial agonists on multiple measures of methamphetamine self-administration will allow insight into the effects of these drugs on the acute reinforcing properties of methamphetamine in Specific Aim 1. Specific Aim 2 and 3 will examine the abstinence phase investigating the potential of partial agonists to prevent different behavioral changes associated with withdrawal. The potential of partial agonists to induce relapse or prevent methamphetamine-induced relapse of methamphetamine-seeking behavior will also be evaluated. Specific Aim 4 will then characterize the transition from moderate to excessive methamphetamine-seeking behavior and investigate whether partial dopamine agonists modify drug intake in rats with a history of drug escalation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE SENSITIZATIO
RECEPTORS
IN
METH-INDUCED
BEHAVIOR
Principal Investigator & Institution: Blackshear, Margaret A.; Tennessee State University 3500 Centennial Blvd Nashville, Tn 37203 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: The major objective of the proposed study is to investigate the role of dopamine D3 receptor mechanisms involved in methamphetamine (METH) behavioral sensitization. Stimulation of dopamine D3 receptors in the limbic/nucleus accumbens area reduces locomotor activity after acute administration. The hypothesis is that chronic METH administration results in adaptive downregulation of D3 receptors in the nucleus accumbens. And downregulation of D3 receptors is believed to play a role in METH sensitization. To test this hypothesis, we will compare the acute and chronic effects of putative D3 receptor agonist, PD 128907 and the more selective D3 agonist, 7 OHDPAT, on METH-induced locomotor activity. To further assess the role of D3 receptors in METH sensitization, METH-induced locomotion will be compared in wildtype and D3 receptor mutant animals. The METH sensitization model, i.e. reverse tolerance paradigm, will be used to assess changes in METH-induced behaviors. Acute and chronic behavioral studies will be conducted in specific aim #1 to define the behavioral effects of selective D3 agonists on METH-induced sensitization. Behavioral studies also will be conducted in specific aim #2 to define the effects of chronic METH administration in dopamine D3 receptor mutant mice. In specific aim #3, dopamine D3 receptor mediated changes in c-fos expression will be used to assess changes in D3 neuronal function the limbic/nucleus accumbens using immunohistochemistry studies. The proposed studies will provide further insight into dopamine receptor mechanisms involved in METH sensitization. Considering that METH sensitization is used as an animal model for amphetamine psychosis, the proposed studies may also have important implications for mechanisms involved in amphetamine psychosis. Additionally, drug sensitization has been implicated in the pathology of drug addiction and drug relapse; the proposed studies may provide further insight into the mechanisms involved.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE REGULATION IN PARKINSONIAN RAT BY GENE THERAPY Principal Investigator & Institution: Kang, Un Jung.; Associate Professor; Neurology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-MAR-2007 Summary: (provided by applicant): L-3,4-dihydroxyphenylalanine (L-DOPA) is the mainstay of therapy for Parkinson's disease (PD). Chronic L-DOPA therapy is limited, however, by the development of motor response complications, such as progressively shorter duration of improvement in akinesia (wearing-off) and the appearance of LDOPA-induced abnormal involuntary movements. Innovative methods of sustained and localized central nervous system (CNS) dopamine delivery may further optimize LDOPA therapy. Such methods are being explored clinically by CNS transplantation studies with fetal dopaminergic neurons and experimentally by neuronal stem cell implants and gene therapy. Our studies during the past funding cycles have defined optimal sets of genes necessary for dopamine replacement using ex vivo gene therapy using genetically modified fibroblasts. We also developed rat behavioral models that are relevant to the akinesia of PD patients. Using akinesia behaviors, we have noted that lesion severity has a major influence on the shortening of the response duration with minor contribution by the chronic intermittent L-DOPA therapy. Therefore, studies proposed in this continuing renewal application will determine the optimal parameters of gene therapy to improve akinesia and minimize and prevent motor response complications. We will use adeno-associated virus vectors to deliver tyrosine hydroxylase and guanosine triphosphate (GTP) cyclohydrolase 1 genes. The optimal combination of anatomical targets for gene therapy to improve akinesia will be defined by examining the effects of gene therapy delivered to basal ganglia structures, such as subthalamic nucleus, substantia nigra par reticulata, that receive dopaminergic inputs, in addition to the striatum. The optimal timing to initiate dopamine replacement gene therapy to forestall development of motor response complications will also be examined. These results will have significant implications beyond dopamine replacement gene therapy proposed here and guide other therapies such as fetal dopaminergic cell transplantation, neurotrophic factor therapy, stem cell therapy, and other CNS targeted delivery systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE TRANSPORTER STRUCTURE-FUNCTION STUDIES Principal Investigator & Institution: Surratt, Christopher K.; Pharmacology and Toxicology; Duquesne University 600 Forbes Avenue Pittsburgh, Pa 15282 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Cocaine initiates its euphoric effects in the brain by binding to the dopamine transporter (DAT), blocking uptake of synaptic dopamine. No specific DAT-ligand contacts have been identified to date, but it is widely held (owing to a previous report) that the DAT transmembrane (TM) 1 aspartic acid residue (D79) forms an ionic interaction with charged nitrogen atoms in both dopamine and cocaine that governs recognition of the ligand. Alternatively, the D79 residue may contribute to a ligand aromatic binding pocket, an ion permeation pore that influences ligand binding, or may simply form intramolecular contacts that retain DAT infrastructure. Toward the goal of elaborating on the nature of DAT substrate and inhibtor binding
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Dopamine
sites, it is critical to determine whether the "ion pair" model for DAT-ligand interactions is credible. The objective of this proposal is to address the validity of the ion pair model, while also assessing alternative potential contributions of the D79 residue to DAT structure and function. D79 DAT mutants that modify side chain size, charge or hydrogen bonding potential will be pharmacologically characterized with a diverse collection of DAT substrates and inhibitors. Other, cysteine-substituted, DAT mutants will test the accessibility of a given position in the DAT polypeptide to cysteine-specific alkylating agents, and whether such alkylation events influence DAT function. By measuring accessibility of an introduced DAT TM 1 (or vicinity) cysteine residue (variably located) in the presence and absence of substrates or inhibitors, the spatial relationship between D79 and DAT substrates and inhibitors will be explored. Because the TM 1 aspartate has been implicated as a contributor to the substrate permeation pore, the substituted cysteine accessibility method will also be used to elaborate on the secondary structure and cell membrane orientation of TM 1 in the vicinity of D79, for which there are multiple models. The proposed experiments should significantly enhance understanding of the TM 1 aspartate residue role in DAT function, as well as advance structure-function studies on the plasma membrane norepinephrine and serotonin transporters which share this residue. Clarification of the role of this residue in recognition of dopamine and cocaine may forward rational design of therapeutics that block cocaine action without significantly interfering with dopamine uptake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE TRANSPORTER--SUBSTRATE & COCAINE BINDING SITES Principal Investigator & Institution: Javitch, Jonathan A.; Associate Professor of Psychiatry and Ph; Psychiatry; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 20-FEB-1998; Project End 31-MAR-2003 Summary: (Applicant's Abstract): Dopamine reuptake at the plasma membrane by the dopamine transporter (DAT) is a major mechanism for terminating dopaminergic synaptic transmission. DAT and the related sodium- and chloride-coupled neurotransmitter transporters combine functional aspects of both G-protein-coupledreceptors and ion channels: namely binding sites for substrate, inhibitors, and ions, and a gated channel or transport pathway through which substrate and ions move. Binding of substrate, sodium and chloride mediates a conformational change which exposes the substrate and ions to the intracellular environment where they are released. Therefore, a water-accessible transport pathway must be formed among the membrane-spanning segments. This pathway should be accessible to hydrophilic reagents applied extracellularly. Although they may not be identical, the binding sites for substrate, ions and inhibitors, such as cocaine, likely lie, at least in part, within this transport pathway. We have developed an approach, the substituted-cysteine-accessibility method, to obtain information about the structure of binding sites and channels by systematically identifying the residues which line the site or channel. Our approach combines: sitedirected mutagenesis to replace putative membrane-spanning segment residues, one at a time, with cysteine; heterologous expression of the mutant; and probing the aqueous surface accessibility of the engineered cysteine residue by its ability to react with small, charged, hydrophilic, lipophobic, sulfhydryl-specific reagents. The long-term goals of this project are to determine the structural bases of the transport of substrate by DAT and its inhibition by drugs such as cocaine. The specific aims are: l) To identify the amino acid residues forming the surface of the cocaine binding site, the dopamine
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binding site, and the transport pathway in DAT. 2) To determine the secondary structure of the membrane-spanning segments containing these residues. 3) To identify conformational changes of the membrane-spanning segments associated with transport. The approach outlined in this proposal will enable us to create a low resolution structural model of DAT, thereby laying a foundation for understanding, at the molecular level, the binding and transport of dopamine and its inhibition by cocaine. This approach might lead to a differentiation of the binding sites for cocaine and for dopamine and thereby facilitate the development of cocaine antagonists which do not inhibit dopamine transport. Furthermore, the approach will provide insights into structure-function relationships for other members of the neurotransmitter transporter family, such as the serotonin transporter and norepinephrine transporter, which are targets for a wide variety of antidepressant drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE/ANGIOSTENSIN HYPERTENSION
RECEPTORS
IN
GENETIC
Principal Investigator & Institution: Felder, Robin A.; Professor of Pathology, Director Medical; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Because the kidney is important in the long term regulation of blood pressure and is the major organ involved in the regulation of sodium homeostasis, many studies have focused on abnormal renal handling of sodium chloride in the pathogenesis of essential hypertension. The autocrine/paracrine agents, dopamine and angiotensin II, work in an opposing manner to regulate renal function. Specifically, dopamine, via dopamine D1 and D3 receptors, is natriuretic while angiotensin II, via AT1 receptors, is antinatriuretic. Increased activity of the renin angiotensin system (RAS) and loss of function in the dopaminergic system lead to sodium retention and hypertension. We have reported that impairment of the renal D1 receptor in mice caused by overexpressing the G protein-coupled receptor kinase type 4 variant, GRK4 A142V, leads to high blood pressure. A similar mechanism may be operating in human essential hypertension; the GRK4 gene locus (chromosome 4p16.3) is linked to and GRK4 variants are associated with hypertension. GRK4 variants impair D1 receptor function in human renal proximal tubules. Expression of GRK4 variants in cell lines replicates the D1 receptor defect noted in renal proximal tubules. Inhibition of GRK4 function or expression normalizes D11 receptor function in and human renal proximal tubule cells/cell lines expressing GRK4 gene variants. Moreover, renal selective prevention of the expression of GRK4 in spontaneously hypertensive rats attenuates the development of hypertension. The overall goal of this PPG is to test the hypothesis that in genetic hypertension the reduction of D1 and D3 receptor function, caused by GRK4, cannot oppose AT1 receptor function leading to increased renal sodium reabsorption and high blood pressure. To accomplish our goal, we have organized a team of investigators, experienced in studies of dopamine and RAS, to elucidate the nature of their gene/gene interactions in health and in hypertension. Project 1 will test the hypothesis that variant GRK4 proteins have increased constitutive activities that desensitize the D1 receptor but not the AT1 receptor. Project 2 will test the hypothesis that salt sensitivity is produced when GRK4 variants desensitize the D1 receptor in the kidney, and that hypertension is produced when variants related to the RAS are also present. Project 3 will test the hypothesis that renal proximal tubule sodium transport is regulated, in part, by an interaction among D1, D3, and AT1
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Dopamine
receptors and that an aberrant interaction occurs in hypertension because of GRK4 variants. Project 4 will test the hypothesis that the natriuresis in AT1A-/- mice is caused by increased D1 and D3 receptor function, and that the decreased dopamine-mediated natriuresis in GRK4 A142V mice is caused by increased AT1, receptor function. These gene/gene interactions are in keeping with the critical roles these receptors play in the polygenic causation of genetic hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE: ALCOHOL RISK AND SENSITIVITY Principal Investigator & Institution: Mccaul, Mary E.; Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Multiple neurotransmitter systems are involved in alcohol reinforcement. These systems are altered by environmental and genetic determinants of risk for alcohol use disorders. Recently, there has been considerable attention to the role of mesolimbic dopamine in alcohol and drug reward. For example, it has been demonstrated that D2 dopamine receptor density is negatively related to stimulant liking, such that individuals with low D2R density report more pleasant effects following stimulant administration than individuals with high D2R density. The proposed research will examine relationships between two key PET-derived measures of the dopamine system (D2 receptor density and dopamine transporter density) and alcohol sensitivity and liking. Additionally, the research will characterize the impact of several well-established predictors of alcoholism risk on these associations. Specific alcoholism risk factors will include family history of alcoholism, high trait anxiety and high excitement seeking. Subjects (N=100) will be social drinkers who do not meet diagnostic criteria for alcohol abuse or dependence but who differ on risk factors known to influence alcoholism development. All subjects will undergo a 13-day inpatient protocol that includes PET imaging of D2R and DAT density, and laboratory measurements of alcohol sensitivity and liking. Alcohol-related measures will include subjective, physiological and psychomotor responses to alcohol ingestion. This project represents an important extension of our earlier and current research on alcoholism. Knowledge gained from both this independent R01 proposal and through interaction with the other IRPG proposals will provide critical new scientific and clinical knowledge on involvement of the dopamine neurotransmitter system in alcohol reward, particularly in persons at differential risk for alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINERGIC MODULATION OF DENDRITIC EXCITABILITY Principal Investigator & Institution: Antic, Srdjan D.; Cellular/Molecular Physiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 10-AUG-2001; Project End 31-JUL-2004 Summary: (From the Applicant's Abstract): The goal of the proposed research is to understand the neuromodulatory effects of dopamine on signal integration in basal and apical dendrites of individual pyramidal neurons. A developing neuronal model for the pathophysiology of schizophrenia, based on the nature of electrophysiological actions of dopamine in the prefrontal cortex, suggests that pyramidal basal and apical dendrites are modulated in a qualitatively different way. According to the model dopamine suppresses the excitability of apical, and enhances the excitability of basal dendrites, resulting in a selective "tuning" of pyramidal neurons to either transcortical-associative,
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or horizontal-intralaminar input pathways. The model suggests the link between prefrontal cortex pyramidal layer 5 neurons and both, (1) clinical symptoms, and (2) postmortem pathological findings in schizophrenic subjects. Direct simultaneous measurements from apical and basal dendrites of prefrontal cortex pyramidal neurons would facilitate our understanding of (1) dopamine effects on dendritic excitability and information processing, and (2) dopamine's role in the pathogenesis of schizophrenia (dopamine hypothesis). We propose to use recently developed multi-site voltagesensitive dye imaging, in order to investigate directly the amplitudes and time courses of synaptic and backpropagating action potentials along basal and apical dendrites, and how these potentials are affected by dopamine D1 and D2 receptor activation. Voltagesensitive dye imaging will also be used to determine whether dopamine induced changes in dendritic excitability can alter the action potential initiation pattern, and whether dopamine differentially modulates basal and apical dendrites within the same neuron. Our efforts are meant to provide the impetus for new therapeutic approaches in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINERGIC MODULATION OF OLFACTORY SIGNAL TRANSDUCTION Principal Investigator & Institution: Lucero, Mary T.; Assistant Professor; Physiology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-JAN-2004 Summary: Olfactory receptor neurons (ORNs) have been assigned the incredible task of distinguishing between over 10,000 odor molecules. Not only must ORNs decipher the quality of odors, they must also provide the brain with intensity information. Recent studies have made considerable progress in identifying and characterizing the components of signal transduction machinery in ORNs. Odors binding to receptor proteins on olfactory cilia initiate a G-protein-mediated second messenger cascade that results in the transient elevation of cAMP or IP3. Both second messengers gate specific ion channels in the ciliary membrane, resulting in the generation of receptor potentials. Olfactory mucus provides the perireceptor environment in which the initial steps of the transduction of a chemical odor signal to an electrical receptor potential occur. Extrinsic autonomic and trigeminal innervation controls mucus secretion and may release neurotransmitters into the mucus. The presence of antioxidant chemicals in the mucus suggests that the mucus environment is permissive for neurotransmitter persistence yet the actions of those neurotransmitters are unclear. The sensitivity of ORNs to cAMPgenerating odors is determined by both the sensitivity of the receptor proteins and the sensitivity of the cyclic nucleotide gated (CNG) channel. One possible role for neurotransmitters released into olfactory mucus is to modulate ORNs odor sensitivity. Potential sites for modulation include the receptor proteins, transduction cascades, and effector channels. The work in this proposal will test the hypotheses that the neurotransmitter dopamine is present in olfactory mucus, acts on D2 dopamine receptors on ORN dendrites and modulates the sensitivity of the system by changing basal levels of cAMP production. Our model suggest that the presence of dopamine in the mucus is under autonomic control and that increases or decreases in dopamine would increase or decrease the sensitivity of ORNs. This model fits with observations that stimulation of the trigeminal system decreases odor sensitivity in frogs, and that the psychophysical perception of odor intensity decreases after exposure to noxious substances (trigeminal stimuli). These studies may be clinically relevant to diseases where dopaminergic pathways are disturbed (Parkinson's) and which display decreased
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Dopamine
olfactory sensitivity as an early symptom. The work in this proposal will determine the modulatory role of dopamine on ORNs and will provide insights into how peripheral dopaminergic pathways may be involved in disease-related reduced olfactory sensitivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS SCHIZOPHRENIA
OF
PCP
IN
A
NOVEL
EXPLANT
MODEL
OF
Principal Investigator & Institution: Thomas, Mark P.; Pharmacology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2004; Project Start 16-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Schizophrenia is thought to result from the altered development of functionally inter-related forebrain structures that mediate goaldirected behavior and cognition. It has been proposed that a primary pathology in these forebrain structures results in a profound disruption of dopaminergic function that can manifest as positive or negative symptoms of schizophrenia. According to this hypothesis, negative symptoms result from diminished dopaminergic function, while positive symptoms are manifested during bouts of abnormally augmented dopaminergic function. The observation that non-competitive antagonists of the NmethyI-D-aspartate (NMDA) type of glutamate receptor (such as phencyclidine) can result in symptoms in normal individuals that are indistinguishable from schizophrenic patients suggests that glutamatergic hypofunction may play a role in the forebrain pathology that leads to dopaminergic dysregulation. In order to study the cellular mechanisms mediating interactions between these glutamatergic forebrain pathways and dopaminergic pathways, a novel rat brain explant preparation has been developed. This preparation contains key regions of the forebrain potentially implicated in schizophrenia as well as dopaminergic midbrain neurons which send fibers into their normal forebrain targets in the striatum and cortex. The goal of this proposal is to utilize this preparation to test the hypothesis that chronic non-competitive NMDA receptor antagonist exposure (mimicking glutamatergic hypofunction) leads to augmented phasic dopaminergic responses in the ventral striatum. The following specific aims will be addressed: (1) Determine the effects of synaptically released dopamine on intrinsic properties of ventral striatal spiny neurons that are known to be altered by exogenously applied dopamine. (2) Determine the effects of synaptically released dopamine on evoked glutamatergic synaptic responses in spiny neurons that are known to be altered by exogenously applied dopamine. (3) Determine whether phasic (burst-evoked) actions of dopamine on intrinsic and synaptic properties of ventral striatal spiny neurons are altered by chronic phencyclidine exposure. These experiments may lead to insights into the cellular mechanisms of action of phencyclidine, and thus indirectly into mechanisms mediating schizophrenic symptoms in patients. This would provide important data useful for the development of more effective antipsychotic medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELECTROANALYSIS MODULATORS
OF
NEUROTRANSMITTERS
AND
Principal Investigator & Institution: Wightman, Robert Mark.; Kenan Professor; Chemistry; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JAN-1980; Project End 31-DEC-2005
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Summary: (Adapted from applicant's abstract) The goals of this research proposal are to develop and use electrochemistry-based probes to monitor neurotransmitters in intact brain tissue. This work is motivated by the belief that monitoring the concentration changes of neurotransmitters in real time provides the most direct way to understand the processes that regulate and control neuronal communication. The neurotransmitter target molecules are dopamine, 5-hydroxytryptamine, and norepinephrine. These molecules are electroactive and are thus a natural target for electrochemical methods. In addition, the three molecules are vital to normal brain function. The information gained by observing these molecules undergoing their job as neurotransmitters will enable their role and their regulation in the brain to be more clearly understood. Furthermore, since real time information is not available for any other neurotransmitters in intact tissue, the information gained will help establish the ways in which neurotransmitters interact with neurons. In addition, we propose to measure local oxygen concentrations and pH. These are both indices of metabolic activity and are closely coupled to neurotransmitter activity. The specific plans of the proposed research are: 1. To improve the response time of carbon-fiber electrodes to neurotransmitter changes. Adsorption of neurotransmitters on carbon-fiber microelectrodes contributes to the sensitivity of these probes in vivo, but it also decreases response time. We propose to characterize the kinetics and mechanism of the adsorption and to minimize the temporal distortion. 2. Design of carbon-fiber surfaces for catecholamine detection. Two surface modification schemes are proposed to improve sensitivity and response time. Carbon surfaces will be exposed to activated carbon to remove impurities and will be covered with quinones. Both methods have been successfully used at large glassy carbon electrodes to improve responses to these neurotransmitters. 3. Probing the regulation of extracellular dopamine. The function of dopamine autoreceptors will be probed to distinguish between autoreceptors regulation of synthesis and release. In addition, we will probe the mechanism of the dopamine transporter in intact tissue. 4. Probing extracellular regulation of norepinephrine. Voltammetric techniques will be used to measure extracellular norepinephrine, an important neurotransmitter in the CNS. The rates of release, uptake, and extrasynaptic diffusion will be studied in several regions of the mouse brain. 5. In vivo electrochemical signals and local blood flow. The carbon fiber electrode can be used to detect extracellular 02 and pH in the brain. 02 levels are related to local blood flow. In this work, we plan to probe the relation between local pH and these other two indices. Our hypothesis is that these measures provide a general view of neuronal activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELECTROPHYSIOLOGY OF THE PREFRONTAL CORTEX Principal Investigator & Institution: O'donnell, Patricio; Proffesor; Ctr/Neuropharmacology/Neurosci; Albany Medical College of Union Univ Albany, Ny 12208 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-MAY-2007 Summary: (provided by applicant): The dopaminergic innervation of the prefrontal cortex is an important component of current hypotheses on the pathophysiology of schizophrenia. Unfortunately, the actions of dopamine in the cortex are not well understood, so we cannot envision a clear picture of how dopamine disturbances can result in symptoms. This field has a large number of inconsistent and often contradictory reports, with the actions of dopamine frequently characterized as inhibitory, excitatory or simply modulatory. We plan to test the hypothesis that dopamine in the prefrontal cortex sustains periods of depolarization (up states) during which synaptic activity is gated. The experiments will address: 1) whether dopamine
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Dopamine
cell activity is correlated with prefrontal cortical up states and whether inactivating the source of dopamine, the ventral tegmental area, eliminates or reduces up states; 2) whether dopamine cells and the prefrontal cortex enhance their synchrony in awake animals during conditions known to drive the dopaminergic projection; 3) whether dopamine can modulate plateau depolarizations resembling up states in a brain slice preparation; 4) whether activation of the mesocortical projection enhances metabolic activity in the prefrontal cortex; and 5) dopamine-glutamate interactions in prefrontal cortical slices obtained from animals with a neonatal ventral hippocampal lesion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL DRINKING IN RATS: ACCUMBAL CIRCUIT ACTIVITY Principal Investigator & Institution: Robinson, Donita L.; Psychiatry; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Candidate: Donita L. Robinson, Ph.D., is an Assistant Professor in the Department of Psychiatry and the Center for Alcohol Studies at the University of North Carolina School of Medicine. Her training has been in analytical chemical methodology for brain measurements of dopamine and ethanol in freely-moving animals. Her immediate goal is twofold: (1) to learn multineuron electrophysiological recording in behaving animals and (2) to learn a technique to measure neuronal firing and subsecond dopamine signaling at the same microelectrede in behaving animals. Her long-term goal is to develop a high-quality, independent research program in ethanol neuropharmacology and behavior, funded by independent extramural grants. This Research Career Award will help Dr. Robinson accomplish these goals by providing solid training in the above methods as well as research support to apply these techniques to ethanol studies. Environment: The University of North Carolina provides laboratory space, equipment, and access to faculty and staff that will allow Dr. Robinson to accomplish the training and research proposed herein. The combined electrophysiology electrochemistry technique was developed by Drs. Regina Carelli and Mark Wightman, who are thus best qualified to sponsor this application. The UNC Center for Alcohol Studies contains many well known experts in ethanol pharmacology and self-administration behavior, including Dr. Clyde Hodge. The sponsoring departments and institution are committed and supportive of Dr. Robinson's development of a successful, independent research program at UNC. Research: The nucleus accumbens (NA) is a limbic-motor integrator, assimilating memory and drive input and coordinating responsive behavioral output. Anatomical and pharmacological evidence indicates that the core and shell subregions of the NA perform overlapping but distinct roles in motivated behavior. The proposed experiments will examine NA core and shell functions in ethanol drinking behavior in rats, with particular focus on how dopamine input modulates NA activity on the millisecond timescale. Finding patterns of neurons in the NA core and shell during operant responding for concurrent ethanol and water will be fully characterized using multi-electrode arrays (Specific Aims 1 and 2). Phasic (subsecond) dopamine activity will be evaluated in the NA core and shell during operant responding for concurrent ethanol and water, while simultaneously recording firing patterns of nearby NA neurons (Specific Aims 3 and 4). Finally, opiate modulation of NA cell firing patterns (Specific Aim 2) and phasic dopamine signals (Specific Aim 4) will be assessed with naltrexone administration before the operant session. Together, these experiments will provide new and valuable information on the interaction of physiology, pharmacology and chemistry in the NA during behavior, comparing ethanol to water reinforcement and core to shell. These studies will best train
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the candidate in a unique and innovative method, and significantly advance our understanding of neural control of ethanol drinking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL, STRESS AND DOPAMINE Principal Investigator & Institution: Jones, Sara R.; Assistant Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Stress may influence the intake of ethanol in humans and animals. Stress appears to predispose rodents to ingest greater amounts of ethanol. However, the relationships between the effects of stress and alcohol on the brain are not fully known. One common neural consequence of both stress and alcohol is the activation of the dopamine system in several brain areas. The areas to be examined in this proposal include the nucleus accumbens (NAc), basolateral amygdala (BLA) and ventral tegmental area (VTA). The NPc and BLA are terminal fields for dopamine neurons that mainly originate in the VTA. We will document the impact of an acutely stressful event, intermittent footshock, on the dopamine system of genetically defined mice. Then we will document the impact of chronic exposure to alcohol on the same parameters. Finally, we will administer both stress and alcohol to the mice and see how the two events interact at the level of the dopamine system We will use microdialysis in freely moving mice and cyclic voltammctry in brain slices to examine the function and dynamics of the dopamine system in detail. These experiments will be performed first on inbred "alcohol-preferring" C57BL/6J mice and "alcohol-avoiding" DBA/2J mice. Not only are there differences between these two strains in preference for drinking oral alcohol, but stress/anxiety measures are also different In addition, dopamine parameters will be measured in mice created by genetic mutation or recombination that have extreme phenotypic responses to stress or ethanol exposure. One known mutation that results in a high-anxiety phenotype is the knockout of the 5HTIA receptor. We are interested in how the dopamine system in 5-HTIA knockout mice is affected by stress, ethanol, or a combination of the two by investigating several genetically different mouse strains. We hope to establish specific molecular relationships between stress and alcohol on dopamine systems in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXTRACELLULAR NEUROCHEMISTRY AND SUBSTANCE ABUSE Principal Investigator & Institution: Michael, Adrian C.; Associate Professor; Chemistry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-APR-2001; Project End 31-MAR-2004 Summary: Adapted from applicant's abstract): Several substances with significant abuse liability in man are known to interact with the nigrostriatal and mesolimbic dopamine pathways of the brain. Examples of such substances include cocaine, amphetamine, and phencyclidine. Detailed knowledge of the manner in which these drugs affect dopaminergic transmission is, therefore, of central importance in understanding the mechanisms that underlie substance abuse. For instance, understanding those mechanisms is a prerequisite for developing new therapeutic strategies for drug abusers. The objective of this application is to investigate how substances of abuse affect the spatiotemporal distribution of dopamine concentrations in the extracellular space of brain structures that received dopaminergic innervation. That distribution is regulated by the kinetics of dopamine release, molecular diffusion, and dopamine uptake. The
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possibility exists, therefore, that drugs might change not just the level of dopamine in the extracellular space but also it spatiotemporal distribution. Information on this aspect of dopaminergic transmission does not presently exist. This research will be conducted by using dopamine-selective microsensors that offer both high spatial and high temporal resolution. With these devices, the impact of drugs on the regulation of the spatiotemporal distribution of dopamine in the extracellular space of the caudate nucleus and nucleus accumbens of the rat will be observed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FETAL ALCOHOL EFFECTS IN MONKEYS: DOPAMINE AND BEHAVIOR Principal Investigator & Institution: Schneider, Mary L.; Professor; Kinesiology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2006 Summary: Fetal alcohol syndrome, (FAS) is the leading known cause of mental retardation today and currently represents an enormous problem for our society. The central question addressed by this proposal is whether moderate alcohol exposure constitutes a danger to the developing offspring. To address this issue, we propose to assess the behavior and physiology in 50 monkeys from four conditions: 1) mothers consumed moderate level alcohol daily throughout pregnancy 2) mothers experienced psychological stress; 3) mothers consumed moderate level alcohol and experienced psychological stress; and 4) mothers consumed sucrose (controls) (Schneider et al., 1997). The specific aims are as follows: 1) to characterize dopamine D2 receptor densities in striata of offspring using in vivo PET imaging techniques 2) to characterize dopamine synthesis in these same cohorts, also using PET imaging, and to uncouple presynaptic synthesis of dopamine from postsynaptic receptor binding availability; 3) to evaluate these monkeys with a standard battery of widely accepted tests and measurements, which index cognitive functioning and behavior; and 4) to determine the effects of a dopamine agonist, methylphenidate, on behavior and cognitive performance in this cohort of monkeys. Our primate model has allowed control of the exact timing and level of alcohol exposure to the fetus and the separation of the effects of alcohol from other life-style factors, such as psychological stress The proposed studies provide a unique and unprecedented opportunity not only to better understand the underlying neurobiology of fetal alcohol effects, but also to discover potential in vivo diagnostic markers for detecting fetal alcohol- induced brain damage. Increasing our understanding of the association between behavior, cognition, and molecular mechanisms of neuronal function in fetal alcohol-exposed primates could aid in early identification and appropriate treatment of children with prenatal alcohol exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENDER DIFFERENCES IN DOPAMINE FUNCTION AFTER TBI Principal Investigator & Institution: Wagner, Amy K.; Physical Medicine and Rehabilitation; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 06-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Traumatic brain injury (TBI) is an epidemic in the United States with survivors often having many decades of productive life loss. An estimated 5.3 million Americans currently live with disabilities resulting from TBI. Despite the fact that about 25% of the population with TBI are women, the large
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majority of clinical and animal research on TBI to date has been with males. Evidence shows that females have more difficulties with post-concussive symptoms and poorer outcome after TBI compared to males. It is suspected that dopamine I (DA) plays a crucial role in working memory and other aspects of executive functioning, and decreases in DA system function after TBI are thought to affect cognitive recovery. Estrogen is well known to play a significant role in dopaminergic functioning, and estrogen has been shown to have a neuroprotective effect acutely after TBI. However, no one has evaluated the effect of estrogen on DA functioning and cognitive recovery from TBI. The goal of this proposal is to evaluate the effects of estrogen on DA pathways in female rodents compared to male rodents after TBI. The effects of methylphenidate on cognitive performance and DA function in females and male rodents after experimental TBI will also be studied. The long-term goal is to delineate the role of estrogen on DA system mediated cognitive deficits in order to develop and optimize new and existing therapies that specifically target and enhance recovery of both males and females after TBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR AGING DISORDERS Principal Investigator & Institution: Geller, Alfred I.; Assistant Professor; Neurology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 31-JAN-2005 Summary: Parkinson's Disease (PD) is a neurodegenerative disorder that primarily affects the aging brain, and the symptoms of PD are principally due to degeneration of nigrostriatal neurons. Current treatments center around restoring striatal dopamine levels and are effective initially. But these treatments gradually lose efficacy, and they do not alter the progression of the Disease. Thus, improved treatments for PD should first, restore the function of the nigrostriatal system, and second, alter progression of the Disease by protecting the remaining nigrostriatal neurons. We have begun to develop a gene therapy treatment for PD. Gene transfer is performed using a helper virus-free Herpes Simplex Virus vector system we pioneered. Two complementary treatment strategies are being implemented. First, restore striatal dopamine levels by producing dopamine in striatal cells. We have shown that expression of tyrosine hydroxylase (TH) in striatal cells supports long-term (1 year) biochemical and behavioral correction of a rat model of PD. Second, protect remaining nigrostriatal neurons by delivering specific neurotrophic factors to these neurons, and enhance the function of the remaining nigrostriatal neurons. Many investigators have shown that glial cell line-derived neurotrophic factor (GDNF) can protect nigrostriatal neurons in rodent and primate models of PD and that brain derived neurotrophic factor (BDNF) has similar capabilities. We have expressed specific neurotrophic factors (NGF, BDNF, NGF receptor) from HSV-1 vectors and demonstrated neuroprotection and other changes in neuronal physiology in specific systems. The function of the remaining nigrostriatal neurons might be enhanced by activating specific signal transduction pathways in these neurons. We have shown that a constitutively active protein kinase C (PKC) increases release of catecholamines from cultured neurons and targeting this PKC to nigrostriatal neurons modulates rotational behavior. We now propose to systematically develop an improved gene therapy for PD by first determining the preferred mechanism to support each treatment strategy and then combining the preferred strategies. The first specific aim will improve biochemical and behavioral correction by systematically investigating the preferred combination of genes (TH, GTP cyclohyrolase, aromatic amino acid decarboxylase, a vesicular monoamine transporter) to support production of dopamine.
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Dopamine
The second specific aim will improve protection of nigrostriatal neurons by systematically investigating the preferred neurotrophic factor(s) (GDNF and/or BDNF) and the preferred site of production. This aim will also examine the function of the remaining nigrostriatal neurons by expressing the constitutively active PKC. The third specific aim will both restore striatal dopamine levels and improve protection of nigrostriatal neurons by systematically combining the preferred strategies from aims 1 and 2. Vectors will be evaluated in cultured cells and then in the rat models of PD for both long-term biochemical and behavioral correction and protection of nigrostriatal neurons. Potential changes in the neurochemistry of nigrostriatal or striatal neurons will also be examined. The long-term goal is to develop human gene therapy for PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ABBERATIONS IN HPRT DEFICIENCY Principal Investigator & Institution: Friedmann, Theodore; Professor; Pediatrics; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Lesch Nyhan disease (LND) is a complex neurobehavioral disease caused by deficiency of the X-linked purine salvage pathway enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT). The abnormal neurological phenotype includes retardation, choreoathetosis and self-injurious behavior. The CNS defects are associated with a basal ganglia deficiency of dopamine (DA). A mouse HPRT knockout model displays a relatively normal neurological phenotype but also shows a deficiency of dopamine in the striatum. Primary cultures of midbrain neurons from HPRT-deficient mice demonstrate a reduction of dopamine levels and dopamine uptake. However, to date there has been relatively little progress toward an understanding of the mechanisms by which HPRT deficiency leads to dopamine deficiency. To identify the potential intermediary role of secondary genes functionally downstream of HPRT activity, we have used microarray gene expression analysis on commercially available MU74 oligonucleotide mouse genome chips that interrogate approximately 12,000 known genes and ESTs. In preliminary comparisons of gene expression in dissected striata from wild type and HPRT-deficient mice, we have detected reproducible changes in the expression of a small number of genes and ESTs, including those encoding translation initiation factors IF2s3 and IF3s1, genes associated with striatal dopaminergic neuron function such as sepiapterin reductase that regulates expression of the tetrahydrobiopterin co-factor of tyrosine hydroxylase, and casein kinase I-epsilon that phosphorylates DARPP-32, the principal striatal target for dopamine function. We have also found preliminary evidence for dysregulation of a number of other cDNAs and ESTs of still uncertain relevance to HPRT deficiency. We propose now to complete a more thorough genome characterization of normal and HPRT-deficient mice, to examine the functional effects of aberrant expression of these genes in cultured midbrain and striatal DA neurons and in transgenic and knockout mice. We also plan to determine the biochemical and neurotransmitter effects of genetic correction of these functions by gene transfer techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTAMATE-DOPAMINE PLASTICITY IN NIGROSTRIATAL INJURY Principal Investigator & Institution: Jakowec, Michael W.; Assistant Professor; Cell & Neurobiology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033
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Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): The MPTP-lesioned mouse serves as an excellent model to study the mechanisms involved in the return of striatal dopamine after basal ganglia injury. The administration of MPTP to C57BL/6 mice leads to the destruction of nigrostriatal dopaminergic neurons and subsequent depletion of striatal dopamine. An advantage of MPTP-lesioning is that the degree of neuronal cell death can be titrated such that remaining dopaminergic neurons may act as a template for repair and recovery in response to the injury. Our hypothesis is that glutamate, acting through altered expression of the AMPA-subtype of receptor, activates the transcription factor phospho-CREB and leads to increased tyrosine hydroxylase expression and axonal sprouting in surviving nigrostriatal dopaminergic neurons. This research proposal is designed to define changes that take place after MPTP injury in the expression of AMPA receptors (including their phosphorylated state), the transcription factor CREB, dopamine receptors (Dl, D2, and D3), and the growth-associated protein GAP-43. The effect of blocking glutamate neurotransmission with the AMPA receptor antagonist GYKI-52466 on these parameters will be determined. The molecular tools of immunocytochemistry, western immunoblotting, in situ hybridization, and anterograde labeling will be used to define the mechanisms involved in the return of striatal dopamine. The long-term goal of these studies is to elucidate features of plasticity following injury to the brain and to identify new therapeutic interventions for the treatment of neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONES, NEURONAL PHOSPHOPROTEINS AND BEHAVIOR Principal Investigator & Institution: Mani, Shailaja K.; Assistant Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-APR-1998; Project End 31-MAY-2009 Summary: (provided by applicant): The ovarian steroid hormones, estradiol and progesterone, regulate functions in the central nervous system resulting in alterations in physiology and reproductive behavior. One means by which estradiol and progesterone exert their neural effects on reproductive behavior is via their interaction with cognate, intracellular receptors functioning as ligand-dependent transcription factors. Studies from my laboratory have shown that in addition to steroid hormones, neurotransmitter dopamine can activate progestin receptors in a ligand-independent manner. Dopamine facilitation of reproductive behavior in female rats and mice occurs by means of crosstalk between membrane receptors for dopamine and intracellular progestin receptors. Signal transduction cascades initiated by dopamine and progesterone, cause an increase in the level of cAMP, PKA activity and phosphorylation of DARPP-32, on Threonine34 in the hypothalamus. In addition to its phosphorylation on Threonine34, DARPP-32 can also be phosphorylated on Threonine75, as well as two Serine residues Ser102 and Ser137. This multisite phosphorylation amplifies the effects of DARPP-32 by converting it into a better substrate for PKA phosphorylation and potentiating its inhibitory effects on the downstream protein phosphatase-1 (PP-1) cascade. While both progesterone and dopamine enhance PKA activity in the hypothalamus, the mechanism(s) by which this increase regulates DARPP-32 inhibition of PP-1 have not been evaluated. This proposal focuses on the mechanisms underlying this multi-site phosphorylation of DARPP-32 by progesterone and dopamine and their effects on female reproductive behavior. Specific aim 1 will evaluate the effects of progesterone and dopamine on DARPP-32 phosphorylation at Thr34 and Thr75 in the hypothalamus and the resultant regulation of
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PP-1 in mediating the biological effects. Specific aim 2 will determine the modulatory role of dopamine and progesterone on the state of phosphorylation of DARPP-32 on Ser102 and Ser 137 in the hypothalamus and examine their effects on the amplification of DARPP-32/PP-1 cascade. Specific aim 3 will examine the effects of progesterone and dopamine on reproductive behavior using mutant mice with point mutations at Thr34, Thr75, Ser102 and Ser137 of DARPP-32. These studies will provide information on the PKA/DARPP-32/PP-1 cascade regulation by progesterone and dopamine in mediating reproductive behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HT/DA SYSTEM INTERACTION IN PSYCHOSTIMULANT DRUG EFFECTS Principal Investigator & Institution: Tancer, Manuel E.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 15-APR-1998; Project End 31-MAR-2004 Summary: (Applicant's Abstract) The neurobiological mechanisms underlying the subjective, reinforcing effects, and discriminative stimulus effects of psychomotor stimulants have been investigated extensively in nonhumans. In general, these studies have indicated that dopaminergic pathways play a crucial role in drug-taking behavior, particularly those pathways that are part of the reward circuitry. However, laboratory studies in humans, such as those involving the administration of specific dopamine agonists and antagonists, have not replicated animal findings and treatment approaches using dopamine antagonists have not been successful. There is increasing evidence that serotonin systems interact with dopaminergic pathways, modulate dopamine release, and can reduce self-administration of psychostimulants in animals. The main goal of the experiments described in this proposal is to increase our understanding of the interaction between serotonin and dopamine systems in mediating the subjective, discriminative stimulus, and reinforcing effects of psychostimulant drugs in humans. This proposal will use three primary approaches to study serotonin/dopamine interactions: first, a drug with mixed serotonin/dopamine properties, 3,4,methylendioxymethamphetamine (MDMA), will be compared with drugs with more selective dopamine (e.g. d-amphetamine) vs. serotonin (e.g., d-fenfluramine) mechanisms of action; second, d-amphetamine and d-fenfluramine will be coadministered in such a way as to produce mixed serotonin/dopamine effects which will be compared to the effects of the compounds administered alone; third, serotoninmediated effects will be blocked by fluoxetine or tryptophan depletion in order to isolate the effects of dopamine with the expectation that serotonin blockade will have differential effects on the subjective, reinforcing, behavioral, and neurochemical effects on d-amphetamine, d-fenfluramine, and MDMA. In addition, these studies will provide objective data on the neurochemical, neurohormonal, subjective and reinforcing effects of MDMA under standardized laboratory conditions. Most importantly for the primary goal of this K08 Award, these studies will provide the PI with the opportunity to receive specialized training in substance abuse research methodology, an essential step in the goal of becoming an independent, productive drug abuse researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN NEURAL STEM CELLS IN PRIMATE PARKINSON'S MODEL Principal Investigator & Institution: Redmond, D Eugene.; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047
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Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): This project will study the hypothesis that human neural stem cells (hNSCs) implanted into monkeys can normalize parkinsonism resulting from the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). These primordial, uncommitted, pluripotent cells can be propagated in large numbers and then safely differentiated into most cell types of the nervous system, including dopamine-producing neurons. NSCs migrate to populate developing or degenerating brain regions, perhaps allowing a more functionally correct and effective reconstruction. Pilot studies now show engraftment of hNSCs in the brain of fetal, neonatal, infant, and adult monkeys, for at least a month. Dopamine depleted adult monkeys showed graftderived tyrosine hydroxylase positive cells and appropriate migration from the site of injection to dopamine-depleted areas. This project will test hypotheses in monkeys: (1) that hNSCs will survive, differentiate, and integrate in the brain of normal adult monkeys without immunological rejection or harmful overgrowth; (2) that hNSCs will eliminate parkinsonism after MPTP treatment, and that the presence of dopamine injury will influence their distribution and fate. NSCs will be identified and quantitated using genetic markers, immunohistochemistry, and multi-synaptic tract tracing. The following will be characterized and compared in normal monkeys and monkeys after MPTP: hNSC survival, migration, cell division, differentiation, connectivity, immunogenicity, stability of expression of a transgene (LacZ), apoptosis, and effect of host environment on all of these. In the dopamine-depleted parkinsonian monkey, dopamine and its metabolite concentrations, autoradiography of dopamine transporters, behavioral reversal of parkinsonism, dose effects, and synaptic connections will be studied over time courses of 7 days, 1, 3, 6, and 12 months. Comparisons will also be made with effects of primary fetal ventral mesencephalic tissue transplants in parkinsonian monkeys from prior and parallel studies. These studies will advance our understanding of the neurobiology and safety of human neural stem cells in a well established clinically relevant primate model of Parkinson's disease, and, if successful, support safe clinical studies in patients with Parkinson's disease in the future. The results will also advance understanding of useful methods for studying and treating a broad range of neurodegenerative, genetic, and traumatic conditions of the nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYSTEMS
INDIVIDUAL
DIFFERENCES IN
MESOLIMBIC DOPAMINE
Principal Investigator & Institution: Meaney, Michael J.; Professor; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 05-SEP-2001; Project End 31-JUL-2004 Summary: (applicant's abstract): There are considerable individual differences in vulnerability for drug abuse. We are exploring the possibility that variation might reflect the effects of early experience on the development of neural systems that mediate drugseeking behavior. While the precise role of the mesocorticolimbic dopamine system in drug self-administration is not clear, this system does appear to be critically involved in drug self-administration. We found that maternal separation in early life decreases dopamine transporter levels and increases extracellular dopamine responses to stress in the n. accumbens in the rat. Likewise, these animals show increased stress-induced sensitization to the locomotor effects of amphetamine and increased behavioral responsivity to cocaine. In the studies proposed here we are examining the effects of maternal separation on dopamine as well as excitatory amino acid responses to stress in the prefrontal cortex. Normally, increased dopamine activity in the prefrontal cortex
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serves to inhibit dopamine release in the n. accumbens. These studies also examine the question of laterality, comparing responses in the left and right regions of the prefrontal cortex. In a second set of studies we are examining the relationship between individual differences in hypothalamic-pituitary-adrenal responses to stress and those observed in the mesocorticolimbic dopamine systems. Adult animals exposed to maternal separation in early life show increased HPA responses to stress that are associated with elevated levels of corticotropin-releasing factor (CRF) mRNA in the paraventricular n. of the hypothalamus and the central n. of the amygdala. Piazza and colleagues have suggested that adrenal glucocorticoids regulate dopamine responses to stress in the n. accumbens as well as behavioral sensitization to repeated stress or psychostimulant drug administration. These studies examine the possibility that the effects of maternal separation on ascending dopamine systems may be mediated, in part, by differences in glucocorticoid and/or CRF activity. Finally, we are examining the potential influence of selected neuropeptide regulators of mesocorticolimbic dopamine systems, such as enkephalin and dynorphin systems. These studies are based on recent findings from the McEwen lab that these neuropeptide systems might mediate individual differences in behavioral responses to stress. We feel that these studies will provide us with an understanding of the way in which early environmental events might contribute to the development of individual differences in neural systems that mediate drug-seeking behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDUCTION OF DOPAMINE NEURONS FROM MONKEY STEM CELLS Principal Investigator & Institution: Zhang, Su-Chun; Assistant Professor; Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Embryonic stem (ES) cells are non-transformed primitive cells derived from early embryos and are capable of essentially unlimited proliferation in an undifferentiated state yet retain the potential to give rise to all cell and tissue types of the body. Thus ES cells provide an almost limitless source for deriving specialized cells for cell therapy. Both human and nonhuman primate ES cell lines have been established by James Thomson of the Wisconsin Regional Primate Research Center and they behave similarly in vitro and in vivo. This proposal will explore the feasibility of using rhesus monkey ES cells (which are available only from the Wisconsin Regional Primate Research Center) as a source to produce dopamine neurons, the major cell type lost in human Parkinson?s disease. First, the ES cells will be directed to neural precursors in a "neural promoting" condition. Second, the ES cellderived neural precursors will be coaxed to become specialized dopamine neurons based on the developmental requirement of midbrain dopamine neurons. Third, the ES cell-derived dopamine neurons will be examined for their therapeutic potential in restoring motor dysfunction in a rat model of Parkinson?s disease. If successful, this exploratory/developmental grant (R21) will be expanded to a five-year proposal to transplant the monkey ES cell-derived dopamine neurons to a monkey model of Parkinson?s disease in the future. Information gained from these studies will be crucial in ultimately utilizing human ES cells to treat neurological illnesses including Parkinson?s disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MONKEYS
INTRANIGRAL
TRANSPLANTATION
IN
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Principal Investigator & Institution: Subramanian, Thyagarajan; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's Abstract): Recent investigations indicate that dopaminergic (DArgic) neurons in the substantia nigra (SN) secrete dopamine not only in their axonal terminals within the striatum but also via their dendrites within the SN pars reticulata (SNr) and that loss of dopamine in the SNr may have a role in the development of parkinsonism in primates. As a corollary, restoration of both nigral and striatal dopamine inputs may produce better recovery of function in Parkinson's disease than restoration of dopamine inputs in the striatum alone. Therefore, the PI proposes to examine the effects of combined DArgic fetal ventral mesencephalic (FVM) cell transplantation into the SN and the striatum in 1-methyl-4-phenyl-1, 2, 3, 6tetrahydropyridine (MPTP)-treated hemiparkinsonian (HP) monkeys and compare the results with FVM transplants in the striatum or SN alone. Animals will be periodically assessed by investigators blinded to the type of transplantation using a behavioral battery of tests (BBT). All animals will be treated with intracarotid MPTP injections to cause a stable HP state and briefly treated with oral levodopa to verify responsiveness to DArgic therapy prior to randomization into 4 equal groups (1-4). Microelectrode recordings of neuronal activity and magnetic resonance imaging (MRI) will be used to guide all transplantation procedures. In specific aim 1 (SA 1), group 1 animals will receive simultaneous FVM transplants into both striatum and the SN, group 2 animals will receive striatal FVM transplants, group 3 animals will receive FVM transplants into the SN and group 4 animals will receive "control" fetal tissue transplants into the SN. Periodic BBT assessments and immunochemical assessment of the transplanted animals compared across groups 1-4 will be used to test the hypothesis that combined striatal and nigral FVM transplants ameliorates parkinsonism to a greater extent than striatal FVM or nigral FVM transplants alone. In SA 2, neuronal recordings will be obtained before and after tissue transplantation from all 4 groups of animals from the SNr and the subthalamic nucleus (STN) and compared. This experiment will examine the hypothesis that striatal FVM transplantation will alter neuronal discharge patterns in both SNr and in the STN, while nigral FVM transplantation will alter neuronal discharge patterns in the SNr only. In SA 3, dopamine levels will be measured in vivo using microdialysis before and after nigral FVM transplantation from the SN and STN in group 3 and group 4 animals. This experiment will test the hypothesis that nigral FVM transplants restore dopamine content in the SN but do not effect dopamine content in the STN. These 3 experiments will objectively evaluate the role of restoring DArgic inputs into the SN in addition to restoring DArgic inputs into the striatum to ameliorate parkinsonian behavioral signs in primates and will help to understand the role of SNr in the pathophysiology of primate parkinsonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IRON DEFICIENCY AND DOPAMINE Principal Investigator & Institution: Beard, John L.; Professor; Nutritional Sciences; Pennsylvania State University-Univ Park 110 Technology Center University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-JUL-2005
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Summary: (provided by applicant): The principal long-term goal of this research is to determine the extent to which iron deficiency anemia (IDA)in early life leads to changes in monoamine biology with related changes in behavior. We will also determine when in development the effect becomes irreversible despite later iron therapy. It is abundantly clear that iron deficiency in early life impairs the biobehavioral development of millions of young children and infants. The previously funded project demonstrated that brain iron deficiency pro and post weaning results in dramatic changes in dopamine metabolism. We demonstrated decreases in dopamine (DA) uptake, DA transporter (DAT) density, and in DA (D1 and D2) receptor density. Iron repletion only restored some of these measures of neurotransmitter metabolism to normal. Certain behaviors, like "exploration" or "anxiety" were related to caudate and prefrontal cortex iron and dopamine variables. Recent pilot studies suggest that metabolism of all central nervous system monoamines (serotonin, norepinephrine, and dopamine) is sensitive to brain iron deficiency. We now hypothesize that brain iron deficiency results in alterations in all three monoamine systems. Specific Aim 1: To demonstrate the extent to which brain iron deficiency during preweaning results in irreversible changes in monoamine metabolism using both short and long term repletion research designs. The hypothesis is that early pre-weaning iron deficiency leads to significant changes in neuronal functioning that are irreversible with iron repletion. Specific Aim 2: To determine the extent to which brain iron deficiency during preweaning alters the emergence of motor and behavioral activities. We will determine the extent to which specific behaviors are related to the alterations in monoamine metabolism measured in Aim 1 through statistical models. Specific Aim 3: To determine the mechanism by which iron deficiency affects the metabolism of moneamine transporters and receptors. These cell culture studies will test the hypothesis that neuronal iron deficiency results in a decrease in the expression of monoamine transporters and potentially monoamine receptors through regulation of gone expression and protein trafficking. This expansion of study to other neurotransmitters will significantly contribute to our knowledge of the effects of iron deficiency on brain functioning in early life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: K OPIOIDS AND DOPAMINE--MECHANISMS OF STIMULANT ABUSE Principal Investigator & Institution: Izenwasser, Sari; Research Professor; Neurology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-JUL-2004 Summary: (Applicant's Abstract) Psychostimulant abuse is a considerable problem in society. Both cocaine and amphetamine are widely used, and the use of methamphetamine on the rise. These psychostimulant drugs produce their reinforcing effects via interactions with the dopamine transporter, cocaine by inhibiting dopamine uptake (the inward flow of dopamine into the neuron), and amphetamines by stimulating dopamine release via reversal of the transporter. These actions result in an increase in extracellular dopamine, which then interacts with dopamine receptors to increase dopaminergic transmission. In order to develop a treatment for the abuse of these substances, it is necessary to find a mechanism by which the activity of the dopamine transporter and dopamine receptors can be regulated. Repeated administration of a selective kappa-opioid agonist produces a down-regulation of the dopamine transporter, and of dopamine D: receptors, suggesting that the kappa-opioid regulation of dopamine neurotransmission might provide a mechanism by which to
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alter the effects of psychostimulants such as cocaine and amphetamine. The specific hypothesis of this proposal is that the dopamine transporter can be regulated via manipulations of kappa-opioid receptors, and that this will alter the neurochemical, and hence the behavioral effects of psychostimulant drugs such as cocaine and amphetamine. Specifically, the anatomical and pharmacological alterations in the dopamine transporter and dopamine receptors, as well as the associated behavioral changes, will be measured following chronic administration of kappa-opioid receptor agonists. We will measure receptor binding using in vitro autoradiography and homogenate binding. Dopamine transporter function will be measured using dopamine uptake and release assays, and dopamine receptor function will be evaluated using adenylyl cyclase and GTPgammaS binding assays. Behavior will be measured using locomotor activity studies. Understanding of the regulation of dopamine neurotransmission by kappa-opioid receptor agonists will provide leads to the development of a therapeutic agent for treating abuse of psychostimulant drugs. Altered dopamine receptor function has been implicated in numerous neurological disorders including schizophrenia, Parkinson's disease, Tourette's syndrome, and Huntington's chorea, in addition to psychostimulant drug abuse. Treatments for most of these syndromes involve use of agonists and antagonists at particular receptors, a state that often leads to marked side effects. Hence, the ability to regulate dopaminergic transmission via alterations of the dopamine transporter would be useful in the treatment of such syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LEVODOPA PHARMACOKINETCA AND PHARMACODYNAMICS Principal Investigator & Institution: Nutt, John G.; Professor; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUL-1984; Project End 31-JUL-2004 Summary: Parkinson's disease (PD) is a common disorder, occuring in 1-2 percent of people over the age of 55. The efficacy of levodopa, our best symptomatic therapy, is limited by the development of motor fluctuations and dyskinesia. Understanding the mechanisms underlying emergence of these motor complications is essential to developing methods to prevent or treat them. The goal of this proposal is to assess the contribution of the remaining striatal monoaminergic terminals to the clinical response to levodopa and its evolution during long-term levodopa therapy. There are three aims. 1) Determine the importance of reuptake of dopamine into residual dompamine terminals by examining the effects of inhibition of the dopamine transporter (DAT) using the DAT inhibitor, methylphenidate. The effects of methylphenidate alone and in combination with levodopa will be examined to determine if dopamine reuptake influences the off drug severity of PD and whether it alters the response to a 2 hour levodopa infusion, specifically, makes it appear more like that observed in advanced PD patients. 2) Determine if serotonin terminals and the serotonin transporter (SERT) assume a role in reuptake and storage of dopamine in advanced PD when the serotonergic terminals become a large portion of the residual stiatal monoaminergic terminals. The effects of paroxetine, a selective SERT inhibitor, on response to a 2 hour levodopa infusions will be examined. 3) Determine if autoreceptors on residual dopamine terminals influence PD severity by examining the response to a step wise infusion with apomorphine, a D-1, D-2 receptor agonist capable of inhibiting motor behavior at low doses in animals. These studies assess the importance of the remaining monoaminergic terminals on the response to levodopa, determine how loss of reuptake
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Dopamine
contributes to the development of motor complications and suggest whether the remaining terminals might be pharmacologically manipulated to therapeutic advantage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIGHT AND DARK ADAPTATION IN THE PRIMATE RETINA Principal Investigator & Institution: Marshak, David W.; Professor; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: The visual system remains responsive over an enormous range of ambient illumination, and this adaptation is accomplished entirely within the retina. While some of these changes in sensitivity are mediated by the rods and cones, themselves, there are also important contributions to adaptation from the other neurons in the retina. Dopamine will be the focus in the first grant period because it is thought to play a critical role in light adaptation, changing the strength of chemical and electrical synapses so that the retina remains sensitive to contrast as the intensity of the background light increases. The major targets of the dopaminergic neurons in mammals, All amacrine cells are known to be uncoupled both by dopamine and b photopic light stimulation. However, it is still uncertain which other effects of light are attributable to dopamine in mammalian retinas and what role, if any, dopamine plays in dark adaptation. Last year, the membrane properties of dopaminergic neurons were described for the first time, and they were found to fire action potentials spontaneously in vitro. Two other surprising, new findings were that, in total darkness, All amacrine cells are uncoupled and dopamine is released from the retina. These data led to the hypothesis that dopaminergic neurons are spontaneously active in total darkness, tonically inhibited in scotopic backgrounds and receive both excitatory and inhibitory input in brighter background. The goal of the proposed experiments is to test elements of this hypothesis more rigorously using computer models. It is clear that dopaminergic retinal neurons pla an important role in human vision since the electroretinogram is abnormal in patients with Parkinson's disease, in which dopaminergic neurons degenerate, and in patients taking neuroleptic drugs that block dopamine receptors. The results of these experiments may also be applicable to dopaminergic neurons elsewhere in the Central nervous system. For example, the effect of dopamine on electrical coupling was discovered in the retina and later found to occur in the brain, as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MAPPING THE D2/D3 DOPAMINE RECEPTOR BINDING SITES Principal Investigator & Institution: Luedtke, Robert R.; Pharmacology & Neuroscience; University of North Texas Hlth Sci Ctr Fort Worth, Tx 761072699 Timing: Fiscal Year 2002; Project Start 20-JUL-2001; Project End 31-MAY-2005 Summary: (Provided by applicant): A variety of neurological and neuropsychiatric disorders appear to be due to disturbance of the dopaminergic system. Since recent studies indicate that Di-like and D4 dopamine receptor selective antagonists are not effective antipsychotics, there is a renewed focus on D3 dopamine receptors as a target for antipsychotic drugs used in the treatment of schizophrenia. In addition, recent studies suggest that the D3 dopamine receptor subtype might be an important target for the development of agents for pharmacotherapeutics that could be used in the rehabilitation of individuals who abuse cocaine. However, it has been difficult to develop selective D3 receptor compounds that can be used for experimental or clinical studies on the role of the D3 dopamine receptor subtype in neuropsychiatric disorders
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or drug abuse because the D2 and D3 dopamine receptors have a high degree of amino acid sequence homology within the transmembrane spanning regions, which construct the neutotransmitter binding site. In collaborative studies, our laboratory has identified a series of structurally related compounds that range from 5- to 50-fold selective for the LB compared to the D2 dopamine receptor subtype. The experiments described in this proposal are designed to identify the amino acid residues within the D2 and LB dopamine receptor binding sites that directly interact with the currently available LB selective compounds. This will be accomplished by preparing mutant receptors structurally related to the D2 and LB dopamine receptor subtypes to precisely define the position of the pharmacophore within the neurotranamitter binding site. The results of these studies will 1) provide information on how our current LB dopamine receptor selective compounds bind to the neumtransmitter binding sate and 2) provide additional structural information that will assist us in the design of novel compounds with increased selectivity for LB dopamine receptors Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ACTION OF DRUGS OF ABUSE--AMPHETAMINE Principal Investigator & Institution: Kuczenski, Ronald L.; Psychiatry; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-JUN-1993; Project End 31-MAR-2005 Summary: (Adapted From The Applicant's Abstract) This application seeks renewal of research support to continue to study the sites and mechanisms of action of psychomotor stimulants. Its general aim is to study the effects of amphetamine on striatal glutamate and dopamine neurotransmission and the sites of termination of glutamate and dopamine axons relative to the different neostriatal output cells. Specifically, it will address three issues related to the effects of systemic amphetamine: the presynaptic mechanisms contributing to neostriatal changes associated with addiction, and the circuitry that brings about the amphetamine-induced increase in neuronal activity of the direct striatal output pathway. The motor effects of these drugs depend on their ability to increase dopamine (DA) transmission. Several motor responses are enhanced by repeated amphetamine administration; a phenomenon termed behavioral sensitization. Changes in the sensitivity of DA somatodendritic and terminal axon autoreceptors may contribute to behavioral sensitization. Experiments are proposed using terminal excitability, an in vivo electro- physiological measure of presynaptic receptor stimulation, and microdialysis to further study the bases for presynaptic changes in nigrostriatal DA axon terminals in sensitized rats. DA terminal fields in nucleus accumbens and prefrontal cortex will also be examined. Alterations in glutamatergic transmission may also be critical in the development of sensitization. Excitability measurements will assess possible presynaptic changes in the glutamatergic afferents to the neostriatum, nucleus accumbens and ventral tegmental area. Other studies will examine the relation between impulse-induced long-lasting changes in presynaptic corticostriatal excitability and postsynaptic expressions of long- term potentiation or depression. Electron microscopic studies are proposed to further elucidate the neostriatal circuitry involving the DA and glutamate afferent systems. It will be determined whether DA inputs onto spiny dendrites are associated with inputs from specific cortical and thalamic regions and if these patterns of convergence differ for spiny neurons identified as belonging to the direct and indirect output pathways. The thalamus is a major excitatory input to the striatum, yet little is known regarding differences in innervation from specific thalamic regions. Differences in the thalamic input onto cholinergic and spiny neurons participating in the two output pathways will
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Dopamine
be examined and the morphology and other afferents of these cells determined. The possibility of nonsynaptic release sites on nigrostriatal DA afferents will be assessed by labeling components of the release mechanism and then correlating them with the locations of dopamine receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF DOPAMINE & SEROTONIN IN TOURETTE SYNDROME Principal Investigator & Institution: Wong, Dean F.; Vice Chair for Research; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) The mechanisms and significance of the dopaminergic and serotonergic neurotransmission systems in Tourette Syndrome (TS) have not been thoroughly investigated and explained. A more complete understanding of their roles in TS would lead to better selection of pharmacological treatments for these patients and provide insight into the pathophysiology of TS. This project will examine pre-, and post- and intrasynaptic dopamine neurotransmission DA transporter (DAT), D2 density (D2Bmax) and DA release (DArel), simultaneously in patients with TS. Serotonin abnormalities will be studied in patients with TS and obsessive-compulsive disorder (OCD), a co-morbid disease. Based on our prior neuroreceptor imaging experience with positron emission tomography (PET) in TS and other neuropsychiatric disorders, we hypothesized that DArel stimulated by an amphetamine challenge will be increased in TS and will correlate with the severity of symptoms (Aim 1). In Aim 2 we will investigate how the relationship between the pre-, post- and intrasynaptic measures of dopamine differ between patients with TS and normal controls. For example, we predict dopamine release and D2 dopamine receptors will both be increased in TS compared to normal subjects. There is a need to establish appropriate serotonin and dopamine/serotonin combinations in the treatment of TS. We hypothesize that there are abnormal serotonin receptors and transporters in TS subjects prior to treatment and that the differences will be most pronounced in subjects with symptoms of OCD. We will examine pre-synaptic serotonin transporters(SERT) and post-synaptic (5HT24R) in TS subjects with and without OCD and compare the results to controls with and without OCD (Aim 3). In Aim 4 we will explicitly examine the relationship of DArel together with the serotonergic measures to explore dopamine serotonin interactions in the same individual. The measurement of pre-, and post- and intrasynaptic dopaminergic parameters has never been performed simultaneously in the same TS subject. Serotonin 5HT24R and SERT have not been studied in same patients with TS and symptoms of OCD. We propose to carry out experiments using PET to establish a more complete understanding of the neurotransmission in TS. This will also help establish new ationales for improved therapeutics in TS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF DRUGS OF ABUSE Principal Investigator & Institution: Kuhar, Michael J.; Candler Professor of Pharmacology; Pharmacology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2004; Project Start 15-APR-1999; Project End 31-MAR-2009 Summary: (provided by applicant): This is an application for a NIDA Research Scientist Award. A long-term research objective is to delineate the neurochemical events that
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underlie drug abuse and dependence. In other words, drugs produce their effects through neurochemicals in the brain, and when taken repeatedly, drugs change the chemical makeup of the brain. The long-term neurochemical changes form the basis of dependence and relapse. When these changes become known, novel strategies for treatments and medications can be developed. The specific goals of this proposal focus on relatively new and relevant neurochemicals, the CART peptides. These peptide neurotransmitters are: found in brain regions related to reward and reinforcement, mobilized by psychostimulant drugs, and appear to mediate or modulate the actions of these drugs by interacting with mesolimbic dopamine. Mesolimbic dopamine is involved in reward and reinforcement for most or all drugs of abuse. Having shown that CART peptides can both mimic or blunt the actions of cocaine, depending on their site of action, and having shown that neurons containing CART interact with mesolimbic dopamine containing neurons, two aims of this project are to elucidate many aspects of the CART-dopamine interaction. The first aim will test the hypotheses that CART in the VTA can release accumbal dopamine, can be stimulated by dopamine and if CART peptides and dopamine receptors are found on the same cells in the nucleus accumbens. Given the evidence that psychostimulants can rapidly modulate CART gene expression in the accumbens, the second aim will identify transcription factor binding sites in the proximal promoter of the CART gene that regulate expression of the CART gene. Finally, because of the need to study the CART receptors, the last aim will attempt to identify the receptor(s) by binding techniques. Taken together, these studies will: clarify the interaction of dopamine and CART, elucidate the regulation of the CART gene in the brain, and hopefully open a new area for study of the CART receptors. Preliminary data indicate that this work is feasible. Since CART peptides are important for stress and feeding and other processes, the findings in these studies will impact other areas as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDIAL PREFRONTAL CORTEX AND COCAINE SENSITIZATION Principal Investigator & Institution: Steketee, Jeffery D.; Associate Professor; Pharmacology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 31-MAR-2005 Summary: Behavioral sensitization, the enhanced motor-stimulant response that occurs with repeated, intermittent exposure to cocaine, has been proposed to play a role in drug craving and relapse. An increased understanding of the mechanisms involved in the development of sensitization may lead to improved pharmacotherapies for drug addiction. It has been suggested that cocaine-induced changes in the ventral tegmental area (VIA) and nucleus accumbens are involved in the initiation and expression of sensitization, respectively. However, recent studies do not entirely support this hypothesis. Thus, the present proposal will test the hypothesis that sensitization results from a decrease in dopamine-mediated glutamate transmission from the medial prefrontal cortex (mPFC). We have reported that depletion of dopamine in the mPFC by 6-hydroxydopamine lesions enhances the motor-stimulant response to cocaine. Follow up studies will determine whether these lesions also enhance glutamate transmission in the mPFC and dopamine and glutamate transmission in regions innervated by the mPFC such as the VTA and nucleus accumbens. A second set of studies will determine whether sensitization to cocaine is associated with changes in dopamine and glutamate transmission in the mPFC using in vivo microdialysis. The temporal relation of neurochemical changes in the mPFC, compared with those previously shown in the nucleus accumbens, will also be assessed. The role of mPFC dopamine in the
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development of sensitization will be further examined by determining the effects of site specific injections of dopamine receptor agonists or antagonists into the mPFC on behavioral and neurochemical responses to cocaine. Preliminary data suggest that sensitization to cocaine may result from a decrease in dopamine receptor function in the mPFC. To determine this, the effects of repeated cocaine exposure on dopamine receptor regulation of adenylyl cyclase activity in the mPFC will be examined. Results of these studies should provide a better understanding of the role the mPFC plays in the development of sensitization to cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATORS OF NICOTINE-MEDIATED DOPAMINE RELEASE Principal Investigator & Institution: Efange, Simon Novoneuron, Inc. 1 Ne 19Th St, Ste 399 Miami, Fl 33136
M.;
Associate
Professor;
Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JAN-2005 Summary: (provided by applicant): The goal of this project is to develop nicotine agonists that selectively modulate central dopaminergic function via a-conotoxin Mllsensitive nicotinic acetylcholine receptors (nAChRs). Nicotinic receptors of this subtype mediate nicotine-induced dopamine release in the nigrostriatal dopaminergic system. Selective activation of these nAChRs therefore constitutes a potentially useful strategy for the management of PD. In preliminary experiments, we have discovered a substituted chroman that stimulates release of dopamine from rat striatal membranes without evoking the release of acetylcholine (ACh) from rat cortex. Moreover, electrophysiologic recordings of Xenopus oocytes expressing human nAChRs confirm the preferential activation of a3b2 nAChRs by this compound. The objective of the present investigation is thus to expand the pool of lead compounds in this structural class. Specifically, we propose to synthesize 8 related substituted chromans and coumarins. These compounds will be screened for 1) binding to alpha3beta2, alpha6/alpha3beta2, alpha4beta2, alpha7, alpha3beta4 and alpha1beta1delta nAChRs; 2) ability to activate these nAChR subtypes in heterelogous expression systems; and 4) their ability to stimulate a-conotoxin MIl-sensitive striatal dopamine release, cortical ACh release and cation (Rb-86) efflux. The most potent and selective activators of aconotoxin MIl-sensitive striatal dopamine release will be used as the starting point for an intensive lead optimization effort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MPFC, N. ACCUMBENS AND REINSTATEMENT OF COCAINE SEEKING Principal Investigator & Institution: Pierce, Chris; Associate Professor; Pharmacol & Exper Therapeutics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 10-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): One of the major determinants of reinstatement of cocaine use among human addicts is acute re-exposure to the drug, which often precipitates cocaine craving and relapse. This grant proposal will use an animal model of cocaine relapse in order to determine the anatomical and pharmacological determinants of reinstatement of cocaine-seeking behavior following a priming injection. These experiments will focus on the nucleus accumbens and medial prefrontal cortex (mPFC); two nuclei know to play important roles in cocaine reinforcement. All experiments will be performed in rats. Specific Aims 1 and 2 will examine the role of
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dopamine in the nucleus accumbens and mPFC in cocaine relapse by administering a priming microinjection of cocaine, selective dopamine reuptake blockers, D1-like or D2like dopamine agonists into the nucleus accumbens or mPFC. In order to assess further the role of specific dopamine receptors in cocaine relapse, selective dopamine receptor antagonists will be administered directly into the nucleus accumbens or mPFC prior to a systemic priming injection of cocaine. Specific Aim 3 will focus on the role of glutamate in reinstatement of cocaine seeking. Although cocaine does not directly influence the glutamate system, recent evidence indicates that ionotropic glutamate receptor agonists administered into the nucleus accumbens reinstate cocaine-seeking behavior. Since the mPFC sends a major glutamatergic projection to the nucleus accumbens, it will be determined if cocaine microinjections into the mPFC reinstate cocaine-seeking behavior by altering glutamate and/or dopamine transmission in the nucleus accumbens. This will be achieved by microinjecting AMPA, NMDA, D1-like or D2-like antagonists into the nucleus accumbens prior to a priming microinjection of cocaine into the mPFC. Collectively, the proposed research will provide fundamental information on the anatomy and pharmacology of relapse to cocaine-seeking behavior and will facilitate the development of effective pharmacological strategies for relapse prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPY/ALCOHOLISM
NEUROBIOL
MECHANISM/ACUPUNCTURE
Principal Investigator & Institution: Ye, Jiang-Hong; Associate Professor Anesthesiology; Anesthesiology; Univ of Med/Dent Nj Newark Newark, Nj 07107
of
Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Alcohol abuse and alcoholism pose serious social and economic problems in the United States and around the world. Despite the increasing number of pharmacotherapies for alcoholism, current treatments have limited success and high rates of relapse. Although acupuncture has shown promising results in alleviating alcohol craving, the mechanism causing this effect remains unclear. Our long-range goal is to understand the neurobiological principles underlying acupuncture therapy for alcoholism. The objective of this proposal is to identify the changes induced by alcohol withdrawal and by acupuncture in rat dopamine neurons of the ventral tegmental area (VTA), a reward center of drug abuse. The central hypothesis is that acupuncture reverses or attenuates the reduction in excitability of dopamine neurons induced by the withdrawal of chronic ethanol administration and thus restores "normal" function of the dopamine system The changes caused by acupuncture can be detected in brain slices. We plan to test our hypothesis and accomplish the objective of this application by pursuing the following two Specific Aims: 1. Identify effects of ethanol withdrawal on dopamine neurons in brain slices. 2. Identify effects of acupuncture on alterations induced by ethanol withdrawals. Research design and methods: To achieve these aims, acupuncture/sham acupuncture will be given to rats withdrawn from chronic alcohol administration. While behavioral responses to withdrawal will be examined in vivo, the neuronal activities will be examined on VTA brain slices, using patch clamp techniques. The proposed work is innovative, because it will use proven modern techniques to elucidate the mechanisms of both acupuncture and its use in treating alcohol addiction. This approach is expected to yield the following outcomes: it will identify the effects of ethanol withdrawal on dopamine neurons in brain slices; optimize parameters of acupuncture to alter the neuronal responses induced by ethanol withdrawal, and elucidate changes induced by acupuncture in dopamine neurons of rats withdrawn from chronic ethanol
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administration. This new knowledge will have a major impact on our understanding of how acupuncture works. The application of this knowledge is expected to improve the effectiveness of acupuncture treatment in alcohol addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROCHEMICAL EFFECTS OF PRENATAL COCAINE IN RAT STRIATA Principal Investigator & Institution: Jackson, Denise; Associate Professor and Director; Psychology; Northeastern University 360 Huntington Ave Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 20-FEB-1998; Project End 31-JAN-2003 Summary: (Applicant's Abstract) This research proposal examines the hypothesis that prenatal cocaine exposure alters nigrostriatal dopamine transmission in rat offspring. The functional integrity of nigrostriatal dopamine neurons after prenatal cocaine exposure will be assessed by measuring endogenous dopamine release and dopaminergic modulation of acetylcholine release from superfused rat striatal slices. Studies will examine the responsiveness of slices to electrical stimulation and to a variety of pharmacological drugs that affect several aspect of transmitter release including reuptake inhibition, receptor stimulation, and receptor blockade. This approach may reveal discrete effects of prenatal cocaine. Studies outlined in this proposal will examine the role of serotonin on dopamine transmission in rats exposed to cocaine prenatally. Earlier research has demonstrated that serotonin can modulate dopamine release from nigrostriatal afferents and striatal acetylcholine release. Recently it has been shown that prenatal cocaine exposure results in serotoninergic hyperinnervation of the striatum. Thus, dopamine transmission after prenatal cocaine exposure may be regulated by an inhibitory influence of these hyperinnervated terminals. Behavioral consequences of prenatal cocaine will be assessed by measuring stereotypy, a behavior that appears to involve striatal cholinergic neurons, in response to dopaminergic, serotonergic, and cholinergic drugs. The results of these studies should enhance our understanding of the effects of prenatal cocaine on interactions between striatal transmitters at neurochemical and behavioral levels. Moreover, examination of the effects of prenatal cocaine on stereotypy may yield valuable insights into postsynaptic consequences of alterations in dopamine transmission from prenatal cocaine exposure. The final group of experiments was designed to examine reported increases in behavioral sensitivity to cocaine in female rats and specifically whether female offspring are exposed to such increases. Investigating the impact o prenatal cocaine in female subjects should further our understanding of the basis for increased sensitivity to cocaine. By characterizing prenatal cocaine effects in prepubertal juvenile rats vs adult female rats, the contribution of female hormones on nigrostriatal interactions and behavior can be assessed. There are several health-related aspects of the studies cited in this proposal. First, by providing insights into alterations of striatal interactions in response to prenatal cocaine, we may be able to draw some parallels between findings in animals and findings in human babies exposed to cocaine in utero. These infants experience tremors and restlessness that may be indicative of changes in nigrostriatal basal ganglia circuitry. Second, evaluation of serotonergic hyperinnervation on dopamine transmission in prenatally cocaine exposed animals could lead to the development of serotonergic drugs to curb alterations in motor activity observed in human infants exposed to cocaine. Third, the results of the studies cited in this proposal may relate to issues involving propensity of children of cocaine-addicted mothers to abuse cocaine and to sex differences in cocaine sensitivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROCHEMICAL ADMINISTRATION
MECHANISMS
OF
ETHANOL
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SELF-
Principal Investigator & Institution: Gonzales, Rueben A.; Pharmaceutics; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The neurochemical mechanisms which underlie ethanol self-administration behavior are not well understood at present. Recent research has suggested that brain systems which mediate reinforcement of behavior are probably involved in the development and promotion of ethanol self- administration. One of the major pathways thought to be involved in reinforcement is the dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc). The goal of the present proposal is to test specific hypothesis about the involvement of dopamine in ethanol self-administration behavior in rats which have been trained to drink pharmacologically relevant amounts of ethanol. The major hypotheses to be tested are: (1) increased dopaminergic activity in the NAcc before or during ingestion underlies the control of ethanol and sucrose self-administration, (2) ethanol produces a different pattern of dopamine output in the NAcc compared with sucrose self- administration, (3) ethanol levels in brain produced by self- administration control, in part, dopamine levels in the NAcc along with the timing and pattern of subsequent ethanol drinking bouts, and (4) the mechanism for ethanol's effects on dopamine output is by increasing the release rather than inhibiting the uptake of dopamine. Five experiments will be carried out to determine (1) the relationship between extracellular dopamine in the NAcc during ethanol or sucrose self- administration in a limited access model, (2) the concentrationeffect relationship between brain ethanol and extracellular dopamine during limited access self-administration, (3) if the change in dopamine during 6 hours of access to ethanol is the same as during 30 minute limited access to ethanol, (4) whether ethanol concentrations in brain are related to extracellular dopamine concentrations during 6 hour access to ethanol, and (5) if i.p. administered ethanol alters the in vivo recovery of dopamine or the true extracellular concentration using quantitative microdialysis methodology (point of no-net-flux). Together the results of these experiments will clarify the potential role of dopamine as a neurochemical mediator in the control of ethanol self- administration under conditions in which the ethanol is clearly reinforcing. In addition, the project will provide direct experimental support for the mechanism by which ethanol affects mesolimbic dopaminergic function in vivo. Increased understanding of the neurochemical mechanisms which underlie ethanol selfadministration behavior may lead to new approaches for therapy of alcohol abuse and alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROMODULATORS AND SIGNALING CASCADES IN RETINA Principal Investigator & Institution: Iuvone, P. Michael.; Professor; Pharmacology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Photoreceptor cells are the primary sensory neurons of the visual system. In addition to being regulated by light, aspects of photoreceptor physiology are subject to control by neuromodulators, such as dopamine, adenosine, somatostatin, and nitric oxide. Much of the data supporting a role for these substances in photoreceptor cell function is pharmacological in nature, obtained from nonmammalian vertebrates, and much remains to be learned about the signaling
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mechanisms involved. Our preliminary data in mouse led to the hypothesis that dopamine, acting on dopamine D4 receptors, plays a major role in regulating cAMP metabolism in photoreceptor cells by Ca 2+ -dependent regulation of adenylyl cyclase and by regulating gene expression for components of the signaling cascade that links light exposure to inhibition of cAMP formation. Preliminary data also show that dopamine plays a major role in adaptive responses of mouse retina to changing illumination, possibly through a cAMP-dependent mechanism. The present goal is to test these hypotheses and to thereby elucidate the signaling mechanisms whereby dopamine produces it's effects on photoreceptor gene expression and retinal function during light- and dark-adaptation. Using mouse retina as an experimental model, we will test the following predictions of hypotheses: (1) Dopamine D4 receptors on photoreceptor cells regulate gene expression of one or more components of the signaling pathway that couples light-exposure to suppression of cAMP synthesis. (2) Dysfunctional cAMP regulation in photoreceptors of dopamine D4 receptor deficient mice alters photoreceptor gene expression profiles and posttranslational modification of key gene products, such as phosducin. (3) Dopamine and light decrease photoreceptor cAMP levels by reducing the activity of Ca 2+ / calmodutin-stimulated adenylyl cyclases. (4) Decreased expression of Ca 2+ / calmodulin-stimulated adenylyl cyclase(s) leads to the abnormalities of light and dark adaptation seen in dopamine D4 receptor deficient mice. The results of these experiments will significantly enhance our understanding of how dopamine and cAMP modulate photoreceptor function, especially light- and dark-adaptation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW CNS DOPAMINE RECEPTOR IMAGING AGENTS Principal Investigator & Institution: Kung, Hank F.; Professor; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-1987; Project End 31-MAY-2003 Summary: The objective of this project is to develop new single photon emission computed tomography (SPECT) imaging agents for evaluating dopaminergic receptors of the central nervous system (CNS) in normal and disease states. In the past funding period, we have reported the first Tc-99m labeled dopamine transporter imaging agent ([99mTc]TRODAT-1). The first dopamine transporter imaging study of a Tc-99m labeled agent in human brain was reported from our group (Eur J Nucl Med 23:1527-1530, 1996). Based on this milestone achievement, we propose to focus on the development of Tc99m labeled D2/D3 dopamine receptor imaging agents. Our objective is to test the hypothesis that it is feasible to prepare Tc-99m labeled "benzamide" derivatives with similar biological properties to those of [11C]raclopride and [123I]IBZM, the most commonly used D2/D3 dopamine receptor imaging agents. To test this hypothesis, a series of benzamide derivatives with chelating side groups will be prepared for complexing with Tc-99m. Specific aims include: 1) Synthesis of the proposed new ligands for radiolabeling. Four groups of benzamide derivatives containing an N2S2 chelating system for complexing TcO(IV) will be prepared. The chelating ligand system will form neutral and lipophilic [99mTc]TcON2S2 complexes, which can pass through the intact blood-brain barrier by a simple diffusion mechanism. The structure-activity relationship of the proposed benzamides will be evaluated. 2) Studies of radiochemistry for preparation of Tc-99m, Tc-99 and Re labeled target molecules. 3) Evaluation or biodistribution in rats and in vitro autoradiography as well as in vitro receptor binding study. 4) In vivo SPECT imaging studies in non-human primates. 5) Evaluation of in vivo metabolism and modeling. 6) Radiation dosimetry calculation and toxicology
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study. 7) Phase I clinical trial in humans. The proposed novel Tc-99m labeled D2/D3 dopamine receptor imaging agents, if successfully developed, can provide valuable tools for studying CNS dopamine receptors in vivo. It is likely that the Tc-99m based agents will be widely distributed and accepted as a routine procedure for differential diagnosis of patients with various CNS diseases, such as Huntington's, Alzheimer's and Parkinson's diseases. In addition, the D2/D3 dopamine receptor imaging agents may provide a novel method to study D2/D3 receptor occupancy, which may be critical in producing extrapyramidal side effects in schizophrenic patients undergoing neuroleptic treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIOD - DOPAMINE INTERACTIONS IN COCAINE ABUSE Principal Investigator & Institution: Daunais, James B.; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: This is a request for a Mentored Research Scientist Development Award (KO1). The proposed research is designed to elucidate the relationship between the opioid system and the dopamine system as a result of exposure to cocaine. The majority of what we know of cocaine's effects on the endogenous opioid system has been based on investigations carried out in rats. These studies may be of limited relevance however, to cocaine abuse in humans, because of the differences in expression of opioid receptors in rat vs human brain, as well as, neuroanatomical and neurochemical differences between these species. Moreover, the effects of self-administration on opioid receptors are largely unknown. A strategy combining in vivo and in vitro imaging methods is proposed to assess neuroadaptations in opioid and dopamine receptors that accompany cocaine self-administration in a primate model of cocaine abuse. The primary focus of the proposed studies is training in positron emission tomography (PET) imaging to map changes in brain receptor function that occur over time as a consequence of cocaine selfadministration and in response to a buprenorphine treatment regimen. One of the strengths of PET is that these parameters can be evaluated longitudinally within the same subjects thereby reducing error that is inherent in a between animal study. The data obtained with PET will be directly compared to data analyzed using in vitro autoradiographic techniques in the same subjects analyzed with PET as well as in groups of animals treated under identical conditions. Because alterations in receptor KD and BMAX values do not always correlate with functional activation of those receptors, the effects of these treatments on functional activation of opioid receptors will also be assessed with the [35S]GTPgammaS autoradiographic method which is used to identify receptor-activated G-proteins. A major strength of this proposal is the utilization of different experimental approaches that complement each other to assess the functional and anatomical distribution of receptors. The multidisciplined nature of this project, which will be conducted under the mentorship of Dr. Robert Mach, and in collaboration with faculty specializing in primate behavior, opioid/cocaine pharmacology and signal transduction, will provide a unique opportunity for the candidate to address issues regarding the long-term effects of cocaine. This project will thus enable the candidate to develop into an independent investigator in the sparsely populated arena of primate neurobiology to investigate the neurobiological substrates underlying the long-term effects of cocaine abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Dopamine
Project Title: PATHOPHYSIOLOGY OF DYSTONIA AND PARKINSONISM Principal Investigator & Institution: Mink, Jonathan W.; Associate Professor, Chief Child Neurolo; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 10-APR-2000; Project End 31-MAR-2004 Summary: Parkinson's disease (PD) affects nearly one million people and dystonia affects up to 500,000 people in North America. It is generally accepted that the motor manifestations of PD are due to degeneration of nigrastriatal dopamine neurons with resulting striatal dopamine depletion. Recent evidence has indicated that dystonia (involuntary muscle contractions that produce twisting postures) can also be associated with deficiencies in striatal dopamine neurotransmission. In monkeys, it has been shown that unilateral striatal dopamine depletion induced by intracarotid injection of MPTP causes a biphasic disorder with transient dystonia followed by stable parkinsonism. The association of both dystonia and parkinsonism with striatal dopamine deficiency raises questions about the fundamental pathophysiology of these conditions. The purpose of this project is to investigate the pathophysiology of parkinsonism and dystonia by recording the activity of globus pallidus neurons before and after the administration of MPTP in monkeys trained to perform a reaching task. Quantitative behavioral methods and [18F]FDOPA PET imaging will be used to measure the severity of parkinsonism and dopamine depletion. The activity of single neurons in globus pallidus internal segment (GPi) and external segment (GPe) will be recording in monkeys before MPTP and in the transient dystonic phase and chronic parkinsonian phase after MPTP. The specific aims are l) to determine the relationship of resting pallidal discharge rates and patterns to dystonia and parkinsonism, 2) to determine if there is expansion of somatosensory receptive fields due to striatal dopamine deficiency that is common to both dystonia and parkinsonism, and 3) to determine specific changes in movement-related neuronal activity that accompany dystonia and parkinsonism. These aims will test specific hypotheses of basal ganglia dysfunction related to dystonia and parkinsonism. The results from this study will complement those from the other projects in this program and will further understanding of the pathophysiology of parkinsonism and dystonia. Better understanding of the pathophysiology may lead to new therapies or improved application of currently available therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEROXYNITRITE IN NEURODEGENERATIVE DISEASES OF AGING Principal Investigator & Institution: Ischiropoulos, Harry; Associate Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 15-APR-1997; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): The activity of Tyrosine Hydroxylase (TH) is essential for the production of catecholamines. During the progression of Parkinson's disease (PD) distinct changes in TH activity and concentration have been described. A decrease in dopamine levels without a loss of either TH immunoreactivity or dopaminergic neurons has been described during the early phase of the disease. The middle stage of the disease is characterized by a loss in dopamine and immunoreactive TH without a loss of dopaminergic neurons. Loss of dopamine, TH and dopaminergic neurons characterize late phase of the disease. These distinct events in PD are faithfully reproduced in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) mouse model of PD. However, the biochemical basis to
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explain the changes in TH, activity and content prior to the death of dopaminergic neurons are not clearly understood. Our published data generated during the last two years of funding has provided a reasonable biochemical explanation for the changes in TH during the early phase of MPTP neurotoxicity. The data revealed that TH is a selective target for nitration. Nitration of tyrosine residues represents a posttranslational protein modification that results from the reaction of nitrating agents with proteins. Nitrating agents such as peroxynitrite are formed during oxidative stress. Oxidative stress has been implicated in the pathogenesis of PD and in the MTPT neurotoxicity. The published data showed that for the first 6 hours post MPTP injection, nitration of a single tyrosine in TH results in the inactivation of the enzyme. The inactivation of TH paralleled the decline in dopamine levels in the mouse striatum whereas the levels of TH protein remain unchanged. However, 12 hours after the last MPTP injection, preliminary data indicated that an apparent non proteolytic, enzymatic process has repaired nitrated TH and this is reflected by an increase in the catalytic activity of the protein and in brain dopamine levels. At the same time the protein levels of TH have declined to nearly 50 percent of control. The loss of protein appears to be mediated by the ubiquitin-proteosome pathway. Based on these preliminary data we formulated the following working hypothesis: Protein nitration (specifically TH) represents a pathophysiology stimulus that is managed by two processes; nonproteolytic repair involving a unique denitrase, and/or protein degradation. Critical aspects of this working hypothesis will be examined by: 1) determining the kinetics of repair and degradation of TH in the mouse MPTP and in the PC12 cell models, 2) purifying and characterizing the brain denitrase activity, and 3) investigating the molecular mechanisms for the proteolytic degration of TH. This application is a natural extension of our previous work that elucidated the biochemical mechanism for the inactivation of tyrosine hydroxylase during the early stages of MPTP toxicity. The proposed experiments will elucidate biochemical, cellular and molecular changes in TH during the middle stages of MPTP toxicity and PD by integrating our experiences with protein nitration chemistry and biological chemistry of reactive species, with Dr. Horwitz's PC12 cell model and Dr. Przedborski's MPTP mouse model. The collaboration between the three different laboratories has been productive. Understanding the basic biochemical and molecular changes in TH during the progression of MPTP and PD will facilitate the development of approaches to correct the functional deficit in dopamine production in PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PET IMAGING OF EXTRASTRIATIAL DOPAMINE LEVELS Principal Investigator & Institution: Kessler, Robert M.; Professor of Radiology; Radiation Oncology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Dopaminergic neurotransmission in cortex, limbic regions and thalamus is believed to be centrally involved in the pathophysiology of schizophrenia, psychostimulant drug abuse, and attention deficit disorder. While there are PET and SPECT methods for evaluating striatal dopamine (DA) release and baseline extracellular DA levels in man, at present there are no well validated methods for studying DA release and baseline extracellular DA levels in extrastriatal regions in man. [18F] fallypride is an extremely potent and selective dopamine D2 radioligand, i.e., a KD of 31 pM for the dopamine D2 receptor, which can be used do delineate and quantitate striatal, thalamic, limbic and cortical dopamine D2 receptors in man. Studies in primates demonstrate that [18F] fallypride is sensitive to levels of d-amphetamine released
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Dopamine
dopamine in both striatum and extrastriatal regions. We propose to perform [18F] fallypride PET studies in 12 normal subjects (ages 18-40, 6M, 6F) prior to and following d-amphetamine administration (0.43mg/kg orally) to study d-amphetamine induced dopamine release in extrastriatal regions. This dose of real d-amphetamine produces decrements in striatal [11C] raclopride binding potentials similar to those seen with a 0.2-0.3 mg/kg IV dose of d-amphetamine with similar variability, but with fewer and less severe side effects. We propose to perform additional [18F] fallypride PET studies in 12 normal subjects (ages 18-40, 6M, 6F) prior to and following a 36-hour course of 56.6 mg/kg alphamethylparatyrosine/24 hours (6 grams over 36 hours for a 70 kg subject) to estimate baseline extracellular dopamine levels in extrastriatal regions. The development of methods for estimating DA release and baseline extracellular DA levels in extrastriatal regions will allow important new research studies in a number of psychiatric and neurological disorders which may allow design and evaluation of new therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PET STUDY OF BIOCHEMISTRY AND METABOLISM OF THE CNS Principal Investigator & Institution: Frey, Kirk A.; Professor of Radiology; Radiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-DEC-1979; Project End 31-JUL-2006 Summary: This Program Project focuses on in vivo neurochemistry of human neurological disorders, emphasizing subcortical structures and their interactions in neurodegenerative and idiopathic functional disorders of movement. Studies in the proposal combine neurochemical phenotypes with functional measures, the latter including motor performance, blood flow activation, neurotransmitter release, ans aspects of sleep physiology. The Program consists of 4 Scientific Projects and 3 Cores. Project by Kilbourn, "New Radiotracers for Neurological PET", will introduce a novel functional approach to assessment of GABAA receptors through allosteric ligands of the chloride ionophore. GABAergic projects are critical components of striatal output and other extrapyrimidal sites. Assessment of GABAA function will complement glucose metabolism studies that may preferentially reflect excitatory glutamatergic pathways. Project by Frey, "Striatal Dopamine and Motor Performance in Aging and Parkinson's Disease" will determine functional motor correlates of nigrostriatal dopaminergic losses in aging and Parkinson's disease and will assess their reversal by acute dopaminergic challenge. Project by Gilman, "Neurochemical and Sleep Disorders in Multiple System Atrophy", will assess the relationships between disrupted sleep in extrapyrimidal neurodegeneration and brain stem cholinergic projections. Project by Albin, "Dopamine Synaptic Mechanisms in Tourette Syndrome", will assess striatal dopaminergic projects and their function from a multi-faceted approach, including measures of their density, their capacity for dopamine re-uptake, their capacity for dopamine release, and an assessment of ambient synaptic dopamine occupancy of D2-type dopamine receptors. Cyclotron/Radiochemistry, Tomography and Data Analysis, and Administrative Core functions support each Project. Overall , the disorders under study in this Program are of unknown pathogenesis and have only symptomatic therapies. The proposed studies will lead to enhanced insight into extrapyrimidal neurochemistry and will address important aspects of dysfunction and disability in these disorders. Novel and improved therapies and new pathophysiological mechanisms and insight may ultimately result. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHOSPHORYLATION TRANSPORTERS
AND
REGULATION
OF
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DOPAMINE
Principal Investigator & Institution: Vaughan, Roxanne A.; Biochem and Molecular Biology; University of North Dakota 264 Centennial Drive Grand Forks, Nd 58202 Timing: Fiscal Year 2003; Project Start 01-JUL-1999; Project End 31-MAR-2008 Summary: (provided by applicant): The dopamine transporter (DAT) is the primary system responsible for clearance of extracellular dopamine from the synaptic space. As such, it performs a key role in terminating synaptic transmission and in regulating the concentration of dopamine available for binding to pre- and post-synaptic dopamine receptors. DATs undergo protein kinase C mediated phosphorylation and display concomitant reductions in dopamine transport, suggesting that DATs undergo phosphorylation-induced functional regulation. This would provide the neuron with a mechanism for fine temporal and spatial control of extracellular dopamine concentrations, and subsequent downstream dopaminergic neural activity. DAT phosphorylation therefore has the potential to profoundly influence normal dopaminergic neurophysiology, and may be related to mechanisms of dopaminergic neurode.qeneration or abuse of psychostimulants such as cocaine, amphetamine, and methamphetamine. Current evidence suggests that PKC-mediated regulation of DAT occurs by modulation of intracellular traffickinq and control of DAT copy numbers at the plasma membrane, but a definitive relationship between DAT phosphorylation and trafficking has not been established. This study proposes te thoroughly characterize DAT phosphorylation properties and define the relationship between DAT phosphorylation and functional regulation. The long term goal of this research is to understand the physiological significance of DAT phosphorylation under conditions of normal neurophysiology and with respect to involvement with drug abuse. The specific aims designed to achieve these goals are: 1. Identify sites of PKC-stimulated phosphorylation on native and expressed DATs using mass spectrometry. 2. Construct mutants with phosphorylation sites changed to non-phosphate acceptors, and examine their intracellu[ar trafficking. 3. Characterize the ability of substrates and psychostimulants such as methamphetamine and cocaine to affect DAT phosphorylation. 4. Identify the endogenous pathways responsible for physiological control of DAT phosphorylation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHOTORECEPTOR RESCUE BY INHIBITION OF DOPAMINE SIGNALING Principal Investigator & Institution: Ogilvie, Judith M.; Associate Research Scientist; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2007 Summary: (provided by applicant): The rod photoreceptors of the rd1 mouse degenerate in vivo or in organ culture by one month of age as a result of a defect in the beta-subunit of the cGMP-phosphodiesterase gene. As with most models of retinitis pigmentosa, the underlying mechanism of degeneration remains poorly understood. Dopamine is a neuromodulator affecting most, if not all, cell types in the vertebrate retina. We have discovered that dopamine antagonists from either the D1- or D2-receptor families completely block the degeneration of photoreceptors in the rd1 retinal organ culture model. Current theoretical models and observations of dopaminergic function fail to explain this surprising result. For example, only the D4 receptor subtype has been
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Dopamine
clearly identified in mouse photoreceptors; yet a D1-family antagonist is equally protective. Also, D1- and D2-family receptors generally act through opposing pathways to modulate the effects of the other; here they give the same result. Finally, dopamine generally has subtle, modulatory effects in the retina; here the effect on cell survival is dramatic and complete - no morphological difference can be detected between wild type and treated rdl organ cultures after 4 weeks, when nearly all of the rods have degenerated in the untreated rd1 culture. We propose experiments to address these differences and to test the significance of our findings in vivo. First, we will determine whether the absence of dopamine receptors can increase photoreceptor survival and function in the rd1 mouse retina in vivo. Secondly, we will address two aspects of the underlying mechanism, first testing a novel hypothesis concerning dopamine receptors, a subtype of the larger G-protein-coupled receptor family. In a recent paradigm shift, Gprotein-coupled receptors, previously thought to function only as monomers, are now recognized to sometimes form heterodimers with atypical pharmacology and function. Such novel characteristics have recently been demonstrated with opioid, GABA, and other GPCRs. The formation of heterodimers comprised of different dopamine receptor subtypes could explain many of the perceived incongruities. We will also determine if D1-family dopamine receptors are present in rd1 photoreceptors. The proposed experiments will generate two important results. First, we will determine the importance of dopamine signaling in photoreceptor degeneration in vivo, which could lead to entirely new therapeutic approaches for retinal degeneration. Secondly, we will investigate the underlying mechanism including testing a dopamine receptor heterodimer-induced model of degeneration which could lead to a new area of investigation in retinal cell biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE SENSITIZATION
OF
D3
DOPAMINE
RECEPTOR
IN
BEHAVIORAL
Principal Investigator & Institution: Richtand, Neil M.; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, augments rodent locomotion in a long-standing fashion. The same dopamine pathways playing an important role in drug dependence and psychosis also play a critical role in sensitization. The role of individual dopamine receptor subtypes in sensitization, however, has not been clearly identified. D3 dopamine receptor stimulation inhibits rodent locomotion. D3 receptor activity may be regulated through expression of an alternatively spliced, truncated receptor isoform (termed "D3nf") altering receptor localization and function via dimerization with the full-length subunit. The central hypotheses for our research are that 1.) repetitive D3 receptor stimulation contributes to development of sensitization through decreased responsivity of D3 receptor-mediated locomotor inhibition; and 2.) increased D3nf expression directs altered receptor localization and subsequent release of D3-receptor mediated inhibition, contributing to expression of sensitization. We will test these hypotheses with the following Specific Aims. In Specific Aim 1,we identify the role of D3 receptors in behavioral sensitization to amphetamine. We test the hypothesis that a homeostatic, compensatory response to D3 receptor stimulation contributes to altered D3 receptor splicing and the development of sensitization by determining the effect of dopamine receptor agonists and antagonists on development of sensitization and D3 receptor isoform expression. In Specific Aim 2,
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we will evaluate behavioral response to D3 receptor antagonists following chronic drug administration. We will measure the behavioral response to D3 receptor blockade, using D3-selective drugs as a tool to measure D3 receptor function. This aim tests the hypothesis that expression of sensitization results in part from release of D3-mediated inhibition, therefore resulting in decreased response to D3 receptor antagonist. In Specific Aim 3, we will determine the consequences of chronic amphetamine administration on D3 dopamine receptor expression. We will measure expression of both full-length D3 receptor and D3nf mRNA, and also measure D3 receptor internalization. This aim tests the hypothesis that chronic amphetamine administration increases D3nf expression, thereby inhibiting full-length D3 receptor function by internalizing the full-length receptor. We expect to demonstrate increased D3nf expression, and increased D3 receptor internalization, following sensitization. This finding would suggest alternative splicing pathways as a novel intervention to prevent sensitization, as well as restore D3-mediated inhibitory function, and would also suggest a biological function for D3nf. Collectively; these studies provide a multi-faceted test of a novel hypothesis of the mechanism underlying long-standing changes in limbicmediated behaviors. These outcomes may suggest new interventions for neuropsychiatric conditions in which dopamine is known to play an important role, including psychosis and drug dependence. Significantly, these studies may also elucidate a previously unrecognized mechanism regulating receptor desensitization and trafficking relevant to other receptor systems and pathological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF ENDOGENOUS OPIOID PEPTIDES IN OPIOID ADDICTION Principal Investigator & Institution: Tseng, Leon F.; Professor; Anesthesiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant) The endogenous opioid peptides appear to play an important role in modulating the bi-directional motivational effects of opioids. These motivational effects of opioids are mediated by the mesolimbic dopamine neurons ascending from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and medial frontal cortex (MFC). Depending on the opioid receptors stimulated, either rewarding or aversive effects of opioids can be demonstrated. The activation of u or &opioid receptors increases the release of dopamine in the NAc or MFC and produces place preference, while activation of K-OpiOid receptors decreases the release of dopainine and produces place aversion. The fmding that opioid antagonist naloxone produces place aversion indicates that the endogenous opioid systems are tonically active in modulating the place conditioning behaviors. The likely endogenous ligands for the reward are b-endorphins, Met-enkephalin and endomorphins, and the endogenous ligand for the aversion is likely to be dynorphin(1-17). Present research is to study the neuronal mechanisms of motivational effects, e.g.place conditioning, of bendorphin, endomorphin-1, endomorphin-2 Met-enkephalin and dynorphin(1-17). Experiments will be mainly performed in rats. Microinjection technique will be used to determine the brain sites Sensitive to these opioids on the production of place preference or aversion. We propose that opioids produce their pharmacological actions in part by releasing endogenous opioid peptides following an initial stimulation of the opioid receptors. Pharmacologically the effects of pretreatment with antibodies against opioid peptides on opioid-induced place conditioning, and biochemically the release of endogenous opioid peptides induced by stimulation of applied opioids will be studied.
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The modulation of dopamine release by opioids will also be studied. Intraventricualr perfusion technique and microdialysis probes will be used to measure the release of opioid peptides into the ventricualr space and the releases of opioid peptides and dopamine from circumscribed regions of the brain. Opioid peptides will be measured by ELISA and dopamine by HLPC coupled with ECD. Antisense ODN to the opioid receptor mRNAs, which inhibit the synthesis of receptor proteins, will be used to identify the types of the receptors, which might be involved in the opioid-induced place preference/aversion. In addition, uL-opioid receptor and preproenkepahlin knockout mice will be used to determine if the u-opioid receptors, Met-enkephalin are involved in place conditioning induced by endogenous opioids. The overall goal of the present research is to determine the role of endogenous opioid peptides in place conditioning. Attempt will be made to seek if there are correlative relationships among brain sites sensitive to opioids for the production of place preference or place aversion and the releases of opioid peptides and dopatnine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SELECTIVE PRENATAL DOPAMINE DAMAGE IN NON HUMAN PRIMATES Principal Investigator & Institution: Elsworth, John D.; Senior Research Scientist; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: Several brains disorders with onset before adulthood are thought to involve irregularities in the development of midbrain dopamine neurons. These include some dystonias, LeschNyhan disease, schizophrenia, and developmental hypoxicischemic injury. As relatively little is known about the ontogeny of primate dopamine neurons, the goal of this proposal is to advance understanding of the early development of these neurons, and the effects and compensations that occur in response to their selective damage. Initial studies will use normal African green monkey fetuses which will span in age from the time just after differentiation of dopamine neurons to the time just before birth. The assays performed will provide data regarding possible critical times in development in which damage to dopamine systems might have longlasting deleterious effects, including periods of natural cell death (apoptosis) in dopamine neurons and synaptogenesis of dopamine neurons with postsynaptic targets. Subsequently, the neurochemically specific protoxin, M11rP, will be given to pregnant monkeys at these times. Fetuses that are exposed to MPTP during a peak of programmed cell death may mimic situation where exaggerated or abnormal natural cell death occurs in dopamine neurons. Other fetuses will be exposed to the effects of MPTP over a substantial proportion of the gestation period, incorporating an extended period of synaptogenesis, which may mimic situations where there are fewer than normal dopamine neurons, or where there are deficits in outgrowth or synapse formation. In humans such developmental abnormalities may occur as a result of genetics, drug abuse, environmental toxins, physical trauma, anoxia or infection. Postmortem measurements in monkey fetuses will include biochemical assays of dopamine neuron number, integrity and function, and will be made just prior to birth. Subsequently we plan to examine the brains of neonates which have been exposed to MPTP in utero, when have reached 6 months of age. In the latter group, behavioral observations and a challenge with Ldopa, will also be carried out to indicate whether the infants show deficits that compromise their survival, and identify potential abnormalities for more detailed behavioral and psychological studies which would need to follow later. We are hopeful that these studies will provide insight into both the normal development of primate
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dopamine neurons, and their response to injury at critical times in ontogeny. Thus, the proposed work may lead ultimately to an animal model for one or more pediatric brain disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONIN CONTROL MECHANISMS OF BASAL GANGLIA FUNCTION Principal Investigator & Institution: Walker, Paul D.; Associate Professor; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) Attempts to develop new and effective treatments for movement disorders such as Parkinson's disease have been hampered by an insufficient knowledge of how basal ganglia receptor systems adapt to the consequences of dopamine depletion. This research focuses on determining the role of upregulated serotonin 2A receptors, which we hypothesize provide a mechanism for serotonin to exert greater control over basal ganglia transmission and locomotor function under conditions of dopamine depletion. Our preliminary studies indicate that the target of the serotonin 2A receptor mechanism is the DIRECT striatonigral pathway which utilizes tachykinin neuropeptides colocalized with GABA. New experiments of this application will test the central hypothesis that: upregulated serotonin 2A receptor signaling provides a mechanism for serotonin to enhance striatonigral transmission under conditions of dopamine depletion which influences basal ganglia function and animal behavior. In Specific Aim 1, we will determine the functional consequences of an upregulated serotonin 2A receptor system on serotonin signal transduction within the dopamine depleted striatum by measuring serotonin 2A receptor binding, its linkage to phosphoinositol hydrolysis, its modulation of striatal membrane excitability, and its ability to trans-synaptically regulate striatal tachykinin and GABA expression. In Specific Aim 2, we will determine if tachykinin striatonigral neurons react to the stimulation of upregulated serotonin 2A receptors in the dopamine depleted animal by increasing tachykinin and GABA transmission in the substantia nigra. We will also study the impact of this regulation on locomotor behavior. Finally, in Specific Aim 3, we will determine how an upregulated serotonin 2A receptor system influences the ability of the striatonigral system to regulate basal ganglia dopamine and GABA metabolism, and how these systems influence behavioral recovery of the dopamine depleted animal. Information obtained from these studies will contribute to a better understanding of basal ganglia function and may change how serotonin pathways are considered when designing new pharmacological strategies for diseases which affect dopamine transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STARTLE KNOCKOUT MICE
GATING
AND
LOCOMOTION
IN
D2-FAMILY
Principal Investigator & Institution: Geyer, Mark A.; Professor; Psychiatry; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Adapted from the Investigator's Abstract) Dopamine neurons that project from the midbrain to cortical and limbic structures modulate attention and information processing functions and contribute to the organization of locomotor behavior. Related behaviors are impaired in patients with schizophrenia and other psychiatric disorders,
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suggesting that alterations in mesocorticolimbic dopamine signaling have pathophysiological relevance in human diseases. D1-like and D2-like dopamine receptors have been implicated in the normal activity of these dopaminergic circuits. The functional distinctions among the 3 cloned members of the D2-like subfamily (D2, D3, and D4) remain elusive, in part because of the limited specificity of pharmacological ligands. Strains of gene knockout mice that lack either the D2, D3, or D4 receptors have been generated as genetic models to understand the functions, at a systems level, of these multiple independent genes. Initial characterizations reveal that the individual receptor knockout strains have many unique behavioral phenotypes, including changes in locomotor behavior and startle response measures of sensorimotor gating deficits seen in schizophrenia. The general hypothesis to be tested is that the D2-like receptor subtypes have selective functional roles in the dopaminergic modulation of information processing, locomotor activity, and the sequential organization of behavior. The specific aims to address this hypothesis are: (1) generate congenic C57BL/6 strains of mutant mice with individual D2, D3, or D4 dopamine receptor knockouts and all permutations of double and triple receptor mutations; (2) characterize the phenotype of each strain of homozygous and heterozygous mice using measures of the amount and patterns of locomotor activity, the response to a novel object, and startle reactivity, habituation, and prepulse inhibition; (3) characterize the effects of amphetamine and selected direct dopamine agonists on the same measures; (4) characterize the effects of amphetamine and selected direct dopamine agonists on patterns of locomotor and exploratory behavior in each of the mutant strains; and (5) characterize the effects of amphetamine and selected direct dopamine agonists on startle reactivity, habituation, and prepulse inhibition in each of the mutant strains of mice. These phenotypic and pharmacological comparisons of D2-subtype knockouts in congenic strains having a common genetic background will provide fundamental information regarding the specific functional roles of D2-like receptors in the regulation of unconditioned behaviors that have particular relevance to both psychotic disorders and psychostimulant abuse. This information will have important implications for the further development of therapeutic approaches to the treatment of both schizophrenia and drug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE-FUNCTION ANALYSIS OF THE D3 DOPAMINE RECEPTOR Principal Investigator & Institution: Kuzhikandathil, Eldo V.; Pharmacology and Physiology; Univ of Med/Dent Nj Newark Newark, Nj 07107 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Provided by applicant): The dopaminergic system and in particular the D3 dopamine receptor have been implicated in the etiology ofneuropsychiatric disorders such as schizophrenia and drug addiction. Studies using genetic, molecul biological and pharmacological techniques suggest that the D3 dopamine receptor plays an important role locomotor activity and behavioral effects involving reinforcement and reward. However the role of L receptor in neuronal signaling and the molecular mechanisms by which it modulates the physiological and behavioral effects are not well understood. It has been proposed that the D3 receptor exerts its phenotyp effects by modulating ion channel function and consequently neuronal signaling. We have recent demonstrated that the human D3 receptor expressed in the AtT-20 neuroendocrine cell line couples endogenous G-protein activated inward rectifier potassium (GIRK) channels and P/Qtype calcium channel thereby modulating spontaneous secretory activity. In this project, we plan to characterize the properties oft] D3 dopamine receptor and identify the
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structural features of the receptor that are involved in coupling to o about channels. Given the limited expression profile of the D3 receptor in vivo, the lack of selective pharmacologic ligands, and the need to evaluate properties of mutated D3 receptors, this study will primarily use the AtT-2 heterologous expression system. In addition, to assess physiological relevance, we will also study the I receptor-ion channel coupling in primary cultures of rat nucleus accumbens neurons using a combination electrophysiology and single cell reverse transcriptase-PCR. To define the properties of the D3 dopamine receptor, we will employ methods such as single cell electrophysiology, mutagenesis and expression recombinant and tagged receptors. We will address three specific aims: (1) Investigate the coupling of I receptor to ion channels in primary neuronal cultures from rat nucleus accumbens; (2) Identify the G-proteins and other regulatory proteins that couple the D3 receptor to ion channels and characterize the domains of t D3 receptor that interact with these proteins; and (3) Determine the molecular mechanisms underlying I receptor desensitization. These experiments will provide a better understanding of the properties of the I dopamine receptor and the molecular mechanisms by which it modulates neuronal signaling. In doing so, ti study will make significant contributions toward ongoing efforts to define the role of D3 receptor neurological disorders such as schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNAPTIC TRANSMISSION IN THE RETINA Principal Investigator & Institution: Yazulla, Stephen; Professor; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-MAY-1979; Project End 31-JUL-2003 Summary: (Adapted from applicant's abstract): Retinal dopamine appears involved in light adaptation in all vertebrates, including human. Dopamine depletion in goldfish retina causes a chronic 100-fold increase in light sensitivity. When the retina is reinnervated with a sparse plexus of dopamine processes, synaptic contact is reestablished with horizontal cells but not with ON bipolar cells. It is hypothesized that synaptic contact is necessary for dopamine control of bipolar cells that are responsible for a normal transition from light-to dark-adaptation. It is predicted that horizontal cell responses to dopamine are independent of direct dopamine innervation, whereas bipolar cells depend upon direct dopamine input. These predictions will be tested in electrophysiological and immunocytochemical studies in control, dopamine-depleted (depleted by intraocular injection of 6-hydroxydopamine) and partially reinnervated retinas. Specific aim 1 is to determine electrophysiological properties (voltage- and ligand-gated) of bipolar cells (using whole-dell recording) and horizontal cells (by intracellular recording) in the retinal slice. Initial focus will be on K+ currents, effects of ascorbate, dopamine D1 ligands and GABA. Specific aim 2 proposes to use immunocytochemistry to determine the content and distribution of transmitter- and channel-specific markers by light and electron microscopy. Initial focus will be on K+ channels, glutamate-, dopamine D1- and GABAc-receptors. In addition, it is proposed to use antibodies against agmatine, a selective permeant of cation channels gated by AMPA/NMDA receptors, to determine the relative activity of horizontal cells and OFF bipolar cells. Specific aim 3 is to test the hypothesis that color opponency of bipolar cells is due to direct input from photoreceptors, rather than feedback from horizontal cells, by determining the chromatically-induced intracellular responses of bipolar and horizontal cells in the retinal slice. This project will provide data regarding: (1) the cellular basis of the acute, chronic and recovery phase of dopamine depletion on luminosity coding, (2) elucidation of a dual mechanism for the control of retinal
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processes by dopamine, i.e., volume and wiring transmission, and (3) the relative contribution of horizontal cells and bipolar cells to luminosity and color coding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE MECHANISM OF COCAINE INDUCED VTA SYNAPTIC PLASTICITY Principal Investigator & Institution: Saal, Daniel B.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2004; Project Start 15-MAY-2004; Project End 31-MAR-2007 Summary: (provided by applicant): Substance abuse is one of the most pressing medical and social issues today. We have previously demonstrated that a single dose of cocaine results in a long-term change in the synaptic strength of the midbrain dopamine neurons. We have now shown that all classes of addictive drugs have a similar effect despite diverse primary mechanisms of action. This proposal is aimed at investigating the mechanisms and the behavioral implications underlying this effect. Specifically, I will ask whether the mechanisms are congruent with the general mechanisms of longterm potentiation as described in the hippocampal literature. I will use a number of tools and paradigms to address this question. GluRI AMPA subtype receptors and calmodulin-dependent protein kinase II (CaMKII) have been shown to be required for LTP. I will use mice that have knockout and diminished function mutations to ask if the mid-brain dopamine cell's response to cocaine also depends on these proteins. I will also develop and use a novel peptide reagent to deliver a CaMKII inhibitor to the brain in vivo to confirm the mutant mouse data. I will define the monoamine receptor(s) required for the cocaine effect using in vivo antagonists. I will also use virally-mediated expression to test if the synaptic enhancement in dopamine cells uses the dynamic machinery for regulating synaptic AMPA receptors as it does in the hippocampus. These studies will help define the relevant parameters for establishing a behavioral correlate to the cocaine effect. Robert Malenka MD PhD will be my primary mentor for this project. He has over twenty years of research experience on the cutting edge of science. He has successfully mentored numerous postdoctoral fellows and K08 recipients. In the long term, I intend to run an independent laboratory in a psychiatry department. I will spend 80 to 90% of my time looking at the physiological processes involved in addiction and using well-defined behavioral models to examine the in vivo effects of molecular manipulations that derive from the physiology. My goal will be to define the molecular players in the addictive process and eventually to find molecular targets for intervention. I will spend ten to twenty percent of my time seeing patients with students and residents in a psychiatry clinic. Designing and carrying out this proposal will clearly prepare me to meet my professional goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ULTRASTRUCTURE INTERACTIONS
OF
MESOLIMBIC
TRANSMITTER
Principal Investigator & Institution: Pickel, Virginia M.; Professor; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-1985; Project End 31-MAY-2003 Summary: Studies conducted over the past nine years of the MERIT award established synaptic inputs to mesolimbic dopaminergic neurons in the ventral tegmental area (VTA) and their targets in the nucleus accumbens (NAc) that are critical for psychostimulant and antipsychotic drug actions. Most importantly, the results show
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that these neurons receive monosynaptic input from terminals containing neurotensin or serotonin (5-HT) and from excitatory prefrontal cortical afferents. Synaptic transmission depends, however, on vesicular packaging and plasmalemmal reuptake of monoamines and on the activation of functionally relevant receptors, whose subcellular distributions are largely unknown. To determine these sites, three studies are proposed using quantitative electron microscopic immunocytochemistry for the localization of sequence-specific antipeptide antisera against recently cloned transporters and receptors. These will be examined in brain tissue from normal adult rats and from animals receiving chronic treatment with haloperidol, a typical antipsychotic drug that blocks dopamine D2 receptors. Study I will test the hypotheses that (1) the levels of the vesicular monoamine transporter (VMAT2) and dopamine transporter (DAT) differ in dendrites of mesolimbic and mesocortical dopaminergic neurons, suggesting differences in their capacity for dendritic dopaminergic transmission. The potential functional sites for neurotensin and dopamine D3 receptor activation also will be examined in relation to neurons that contain dopamine, D2 receptors or gamma-aminobutyric acid (GABA), the neurotransmitter present in non-dopaminergic neurons in the VTA and in most targets of dopaminergic terminals in the NAc. Study II will test the hypothesis that 5HT2A receptors, which are major binding sites for certain atypical antipsychotic drugs, are present in dendrites of dopaminergic neurons in the VTA and/or GABAergic neurons in NAc. The localization of the serotonin transporter (SERT) will be examined in the limbic shell and motor core of the NAc to determine whether there are regional variations that may affect local availability of extracellular serotonin. Study III will determine whether dopamine D2 and/or D3 receptors are present in axon terminals derived from the prefrontal cortex or their postsynaptic targets in the NAc. This study will also test the hypotheses that (1) N-methyl-D-aspartate (NMDA) glutamate receptors and D2 receptors are present in the same dendritic spines, and (2) chronic treatment with haloperidol produces selective changes in NMDA containing spines of GABAergic neurons in the motor striatum. Together, the results will contribute to our understanding of the pathophysiology and treatment of hyperkinetic movement disorders and schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “dopamine” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for dopamine in the PubMed Central database:
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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[alpha]-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviralbased model of Parkinson's disease. by Lo Bianco C, Ridet JL, Schneider BL, Deglon N, Aebischer P.; 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125054
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5,7-Dihydroxytryptamine identifies living dopaminergic neurons in mesencephalic cultures. by Silva NL, Mariani AP, Harrison NL, Barker JL.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282183
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6-Hydroxydopamine lesions of rat substantia nigra up-regulate dopamine-induced phosphorylation of the cAMP-response element-binding protein in striatal neurons. by Cole DG, Kobierski LA, Konradi C, Hyman SE.; 1994 Sep 27; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44867
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A common action of clozapine, haloperidol, and remoxipride on D1- and D2dopaminergic receptors in the primate cerebral cortex. by Lidow MS, Goldman-Rakic PS.; 1994 May 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43783
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A common uptake system for serotonin and dopamine in human platelets. by Omenn GS, Smith LT.; 1978 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371758
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A cysteine residue in the third membrane-spanning segment of the human D2 dopamine receptor is exposed in the binding-site crevice. by Javitch JA, Li X, Kaback J, Karlin A.; 1994 Oct 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45018
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A Drosophila dopamine 2-like receptor: Molecular characterization and identification of multiple alternatively spliced variants. by Hearn MG, Ren Y, McBride EW, Reveillaud I, Beinborn M, Kopin AS.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137921
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A HincII RFLP in the human D4 dopamine receptor locus (DRD4). by Kennedy JL, Sidenberg DG, Van Tol HH, Kidd KK.; 1991 Oct 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329013
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A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. by Smidt MP, van Schaick HS, Lanctot C, Tremblay JJ, Cox JJ, van der Kleij AA, Wolterink G, Drouin J, Burbach JP.; 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24304
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A Mechanism for Amphetamine-Induced Dopamine Overload. by [No authors listed]; 2004 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=368179
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A new TaqI RFLP within intron 2 of human dopamine D2 receptor gene (DRD2). by Parsian A, Fisher L, O'Malley KL, Todd RD.; 1991 Dec 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329373
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A Novel Nonneuronal Catecholaminergic System: Exocrine Pancreas Synthesizes and Releases Dopamine. by Mezey E, Eisenhofer G, Harta G, Hansson S, Gould L, Hunyady B, Hoffman BJ.; 1996 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38392
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A Paradoxical Regulation of the Dopamine D3 Receptor Expression Suggests the Involvement of an Anterograde Factor from Dopamine Neurons. by Levesque D, Martres M, Diaz J, Griffon N, Lammers CH, Sokoloff P, Schwartz J.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42591
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A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes. by Ilani T, Ben-Shachar D, Strous RD, Mazor M, Sheinkman A, Kotler M, Fuchs S.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14638
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A possible substrate for dopamine-related changes in mood and behavior: Prefrontal and limbic effects of a D3-preferring dopamine agonist. by Black KJ, Hershey T, Koller JM, Videen TO, Mintun MA, Price JL, Perlmutter JS.; 2002 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139278
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A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6tetrahydropyridine. by Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ.; 1983 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=384076
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A Targeted Mutation of the D3 Dopamine Receptor Gene is Associated with Hyperactivity in Mice. by Accili D, Fishburn CS, Drago J, Steiner H, Lachowicz JE, Park B, Gauda EB, Lee EJ, Cool MH, Sibley DR, Gerfen CR, Westphal H, Fuchs S.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39888
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Actions of dopamine and dopaminergic drugs on cloned serotonin receptors expressed in Xenopus oocytes. by Woodward RM, Panicker MM, Miledi R.; 1992 May 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49152
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Activation of a D2 receptor increases electrical coupling between retinal horizontal cells by inhibiting dopamine release. by Harsanyi K, Mangel SC.; 1992 Oct 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50097
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Activation of ATP-sensitive K+ (KATP) channels by H2O2 underlies glutamatedependent inhibition of striatal dopamine release. by Avshalumov MV, Rice ME.; 2003 Sep 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=208826
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Adenosine receptor blockade reverses hypophagia and enhances locomotor activity of dopamine-deficient mice. by Kim DS, Palmiter RD.; 2003 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=298775
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Agonist-Induced Desensitization of Dopamine D1 Receptor-Stimulated Adenylyl Cyclase Activity is Temporally and Biochemically Separated from D1 Receptor
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Internalization. by Yk.Ng G, Trogadis J, Stevens J, Bouvier M, O'Dowd BF, George SR.; 1995 Oct 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40755 •
Agonist-induced subsensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum. by Memo M, Lovenberg W, Hanbauer I.; 1982 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346691
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Altered accumbens neural response to prediction of reward associated with place in dopamine D2 receptor knockout mice. by Tran AH, Tamura R, Uwano T, Kobayashi T, Katsuki M, Matsumoto G, Ono T.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124410
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Altered Striatal Function in a Mutant Mouse Lacking D1A Dopamine Receptors. by Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP, Bartlett PF, Jose PA, Sibley DR, Westphal H.; 1994 Dec 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45479
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Amphetamine-induced loss of human dopamine transporter activity: An internalization-dependent and cocaine-sensitive mechanism. by Saunders C, Ferrer JV, Shi L, Chen J, Merrill G, Lamb ME, Leeb-Lundberg LM, Carvelli L, Javitch JA, Galli A.; 2000 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18764
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Amplification of dopaminergic signaling by a positive feedback loop. by Nishi A, Bibb JA, Snyder GL, Higashi H, Nairn AC, Greengard P.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18851
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An astroglia-linked dopamine D2-receptor action in prefrontal cortex. by Khan ZU, Koulen P, Rubinstein M, Grandy DK, Goldman-Rakic PS.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29365
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Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia. by Schalling M, Friberg K, Seroogy K, Riederer P, Bird E, Schiffmann SN, Mailleux P, Vanderhaeghen JJ, Kuga S, Goldstein M, et al.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54969
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Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. by Klein C, Brin MF, Kramer P, Sena-Esteves M, de Leon D, Doheny D, Bressman S, Fahn S, Breakefield XO, Ozelius LJ.; 1999 Apr 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21836
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Attention deficit /hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. by Swanson J, Oosterlaan J, Murias M, Schuck S, Flodman P, Spence MA, Wasdell M, Ding Y, Chi HC, Smith M, Mann M, Carlson C, Kennedy JL, Sergeant JA, Leung P, Zhang YP, Sadeh A, Chen C, Whalen CK, Babb KA, Moyzis R, Posner MI.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18305
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Atypical antipsychotic drugs selectively increase neurotensin efflux in dopamine terminal regions. by Radke JM, Owens MJ, Ritchie JC, Nemeroff CB.; 1998 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21665
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Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. by Vila M, JacksonLewis V, Vukosavic S, Djaldetti R, Liberatore G, Offen D, Korsmeyer SJ, Przedborski S.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30226
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Bidirectional regulation of Na+,K(+)-ATPase activity by dopamine and an alphaadrenergic agonist. by Ibarra F, Aperia A, Svensson LB, Eklof AC, Greengard P.; 1993 Jan 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45591
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Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo. by Altar CA, Boylan CB, Jackson C, Hershenson S, Miller J, Wiegand SJ, Lindsay RM, Hyman C.; 1992 Dec 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50547
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Brain-derived neurotrophic factor increases the electrical activity of pars compacta dopamine neurons in vivo. by Shen RY, Altar CA, Chiodo LA.; 1994 Sep 13; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44718
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Calcium alters the sensitivity of intact horizontal cells to dopamine antagonists. by Van Buskirk R, Dowling JE.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346413
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cAMP-mediated decrease in K+ conductance evoked by serotonin and dopamine in the same neuron: a biochemical and physiological single-cell study. by Deterre P, Paupardin-Tritsch D, Bockaert J, Gerschenfeld HM.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347464
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Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. by Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H, Srinivasan A, Ruberg M, Evan GI, Agid Y, Hirsch EC.; 2000 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16023
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Cellular responses to psychomotor stimulant and neuroleptic drugs are abnormal in mice lacking the D1 dopamine receptor. by Moratalla R, Xu M, Tonegawa S, Graybiel AM.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26239
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Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients. by Kwak YT, Koo MS, Choi CH, Sunwoo IN.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29096
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Chaotic behavior in dopamine neurodynamics. by King R, Barchas JD, Huberman BA.; 1984 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=344803
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Characterization of a dopamine receptor (DA2K) in the kidney inner medulla. by Huo T, Ye MQ, Healy DP.; 1991 Apr 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51407
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Characterization of anti-peptide antibodies for the localization of D2 dopamine receptors in rat striatum. by McVittie LD, Ariano MA, Sibley DR.; 1991 Feb 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51034
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Characterization of Subtype-Specific Antibodies to the Human D5 Dopamine Receptor: Studies in Primate Brain and Transfected Mammalian Cells. by Bergson C, Mrzljak L, Lidow MS, Goldman-Rakic PS, Levenson R.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42188
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Characterization of the 5' flanking region of the human D1A dopamine receptor gene. by Minowa MT, Minowa T, Monsma FJ Jr, Sibley DR, Mouradian MM.; 1992 Apr 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48800
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Chimeric Dopamine-Norepinephrine Transporters Delineate Structural Domains Influencing Selectivity for Catecholamines and 1-Methyl-4-Phenylpyridinium. by Buck KJ, Amara SG.; 1994 Dec 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45483
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Chlorpromazie and Dopamine: Conformational Similarities that Correlate with the Antischizophrenic Activity of Phenothiazine Drugs. by Horn AS, Snyder SH.; 1971 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=389413
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Chronic Morphine Induces Visible Changes in the Morphology of Mesolimbic Dopamine Neurons. by Sklair-Tavron L, Shi W, Lane SB, Harris HW, Bunney BS, Nestler EJ.; 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38308
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Ciliary Neurotrophic Factor Prevents Degeneration of Adult Rat Substantia Nigra Dopaminergic Neurons in vivo. by Hagg T, Varon S.; 1993 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46919
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Circadian modulation of dopamine receptor responsiveness in Drosophila melanogaster. by Andretic R, Hirsh J.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26529
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c-Jun mediates axotomy-induced dopamine neuron death in vivo. by Crocker SJ, Lamba WR, Smith PD, Callaghan SM, Slack RS, Anisman H, Park DS.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60880
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Cloning of ligand-specific cell lines via gene transfer: identification of a D2 dopamine receptor subtype. by Todd RD, Khurana TS, Sajovic P, Stone KR, O'Malley KL.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298661
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Cloning of the cDNA and gene for a human D2 dopamine receptor. by Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, BurkeHowie KJ, Bunzow JR, Server AC, et al.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298581
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Cloning of the cocaine-sensitive bovine dopamine transporter. by Usdin TB, Mezey E, Chen C, Brownstein MJ, Hoffman BJ.; 1991 Dec 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53095
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Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. by Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT Jr, Caron MG.; 1991 Sep 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52326
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Cocaine alters the accessibility of endogenous cysteines in putative extracellular and intracellular loops of the human dopamine transporter. by Ferrer JV, Javitch JA.; 1998 Aug 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21322
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Cocaine reward models: Conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. by Sora I, Wichems C, Takahashi N, Li XF, Zeng Z, Revay R, Lesch KP, Murphy DL, Uhl GR.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22727
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Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens. by Weiss F, Maldonado-Vlaar CS, Parsons LH, Kerr TM, Smith DL, Ben-Shahar O.; 2000 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18240
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Control of lactotrop proliferation by dopamine: Essential role of signaling through D2 receptors and ERKs. by Iaccarino C, Samad TA, Mathis C, Kercret H, Picetti R, Borrelli E.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137917
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Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. by Smith PD, Crocker SJ, Jackson-Lewis V, Jordan-Sciutto KL, Hayley S, Mount MP, O'Hare MJ, Callaghan S, Slack RS, Przedborski S, Anisman H, Park DS.; 2003 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=263868
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D1 and D2 dopamine receptor mRNA in rat brain. by Weiner DM, Levey AI, Sunahara RK, Niznik HB, O'Dowd BF, Seeman P, Brann MR.; 1991 Mar 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51125
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D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines. by Smiley JF, Levey AI, Ciliax BJ, Goldman-Rakic PS.; 1994 Jun 7; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44068
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D1A, D1B, and D1C dopamine receptors from Xenopus laevis. by Sugamori KS, Demchyshyn LL, Chung M, Niznik HB.; 1994 Oct 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45056
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D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei. by Weaver DR, Rivkees SA, Reppert SM.; 1992 Oct 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50093
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D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system. by Lankford KL, DeMello FG, Klein WL.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280472
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D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system. by Lankford KL, DeMello FG, Klein WL.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280095
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D2 dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons. by Yan Z, Feng J, Fienberg AA, Greengard P.; 1999 Sep 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18081
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Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria. by Keung WM, Vallee BL.; 1998 Mar 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19293
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Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers. by Bannon MJ, Pruetz B, Manning-Bog AB, Whitty CJ, Michelhaugh SK, Sacchetti P, Granneman JG, Mash DC, Schmidt CJ.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122957
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Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat. by Kinoshita S, Sidhu A, Felder RA.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304064
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Depression of Ventilation by Dopamine in Man EVIDENCE FOR AN EFFECT ON THE CHEMORECEPTOR REFLEX. by Welsh MJ, Heistad DD, Abboud FM.; 1978 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372584
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Differences between high-affinity forskolin binding sites in dopamine-rich and other regions of rat brain. by Poat JA, Cripps HE, Iversen LL.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280175
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Differential expression of autoreceptors in the ascending dopamine systems of the human brain. by Meador-Woodruff JH, Damask SP, Watson SJ Jr.; 1994 Aug 16; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44593
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Differential regulation of neuropeptide mRNA expression in intrastriatal striatal transplants by host dopaminergic afferents. by Campbell K, Wictorin K, Bjorklund A.; 1992 Nov 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50364
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Differential vulnerability of primate caudate-putamen and striosome-matrix dopamine systems to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine. by Moratalla R, Quinn B, DeLanney LE, Irwin I, Langston JW, Graybiel AM.; 1992 May 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48971
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Direct demonstration of a correspondence between the dopamine islands and acetylcholinesterase patches in the developing striatum. by Graybiel AM, Pickel VM, Joh TH, Reis DJ, Ragsdale CW Jr.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348891
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Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro. by Ishibashi M, Yamaji T.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370889
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Direct visualization and cellular localization of D1 and D2 dopamine receptors in rat forebrain by use of fluorescent ligands. by Ariano MA, Monsma FJ Jr, Barton AC, Kang HC, Haugland RP, Sibley DR.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298324
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Distinct presynaptic control of dopamine release in striosomal and matrix areas of the cat caudate nucleus. by Kemel ML, Desban M, Glowinski J, Gauchy C.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298421
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Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. by Tremblay L, Kemel ML, Desban M, Gauchy C, Glowinski J.; 1992 Dec 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50520
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Distinct Roles for G[alpha]i2 and G[beta][gamma] in Signaling to DNA Synthesis and G[alpha]i3 in Cellular Transformation by Dopamine D2S Receptor Activation in BALB/c 3T3 Cells. by Ghahremani MH, Forget C, Albert PR.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85319
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Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites. by Lindgren N, Usiello A, Goiny M, Haycock J, Erbs E, Greengard P, Hokfelt T, Borrelli E, Fisone G.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153088
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Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana. by Baumann O, Dames P, Kuhnel D, Walz B.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117224
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Dopamine (3-Hydroxytyramine) Metabolism in Parkinsonism. by Goodall M, Alton H.; 1969 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297487
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Dopamine (3-Hydroxytyramine) Replacement and Metabolism in Sympathetic Nerve and Adrenal Medullary Depletions After Prolonged Thermal Injury. by Goodall M, Alton H.; 1969 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322408
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Dopamine [beta]-hydroxylase deficiency impairs cellular immunity. by Alaniz RC, Thomas SA, Perez-Melgosa M, Mueller K, Farr AG, Palmiter RD, Wilson CB.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26773
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Dopamine alters glutamate receptor desensitization in retinal horizontal cells of the perch (Perca fluviatilis). by Schmidt KF, Kruse M, Hatt H.; 1994 Aug 16; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44591
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Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells. by Meister B, Fryckstedt J, Schalling M, Cortes R, Hokfelt T, Aperia A, Hemmings HC Jr, Nairn AC, Ehrlich M, Greengard P.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298216
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Dopamine- and cAMP-Regulated Phosphoprotein DARPP-32: Phosphorylation of Ser-137 by Casein Kinase I Inhibits Dephosphorylation of Thr-34 by Calcineurin. by Desdouits F, Siciliano JC, Greengard P, Girault J.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42282
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Dopamine and depolarizing agents regulate the state of phosphorylation of protein I in the mammalian superior cervical sympathetic ganglion. by Nestler EJ, Greengard P.; 1980 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350528
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Dopamine as a Synaptic Transmitter and Modulator in Sympathetic Ganglia: A Different Mode of Synaptic Action. by Libet B, Tosaka T.; 1970 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283257
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Dopamine controls the firing pattern of dopamine neurons via a network feedback mechanism. by Paladini CA, Robinson S, Morikawa H, Williams JT, Palmiter RD.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151432
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Dopamine D1 /D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons. by Seamans JK, Durstewitz D, Christie BR, Stevens CF, Sejnowski TJ.; 2001 Jan 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14585
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Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. by Gines S, Hillion J, Torvinen M, Le Crom S, Casado V, Canela EI, Rondin
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Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A. by Lin R, Karpa K, Kabbani N, Goldman-Rakic P, Levenson R.; 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33197
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Dopamine D2 receptors in the cerebral cortex: distribution and pharmacological characterization with [3H]raclopride. by Lidow MS, Goldman-Rakic PS, Rakic P, Innis RB.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297850
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Dopamine D2 receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice. by Kruzich PJ, Grandy DK.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=400732
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Dopamine decreases conductance of the electrical junctions between cultured retinal horizontal cells. by Lasater EM, Dowling JE.; 1985 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=397699
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Dopamine during [alpha]- or [beta]-Adrenergic Blockade in Man HORMONAL, METABOLIC, AND CARDIOVASCULAR EFFECTS. by Lorenzi M, Karam JH, Tsalikian E, Bohannon NV, Gerich JE, Forsham PH.; 1979 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371954
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Dopamine enhances both electrotonic coupling and chemical excitatory postsynaptic potentials at mixed synapses. by Pereda A, Triller A, Korn H, Faber DS.; 1992 Dec 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50703
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Dopamine genes and attention-deficit hyperactivity disorder: a review. by DiMaio S, Grizenko N, Joober R.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161723
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Dopamine induces neurite retraction in retinal horizontal cells via diacylglycerol and protein kinase C. by Rodrigues PD, Dowling JE.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=55239
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Dopamine Inhibits Angiotensin-Stimulated Aldosterone Biosynthesis in Bovine Adrenal Cells. by Mc Kenna TJ, Island DP, Nicholson WE, Liddle GW.; 1979 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372116
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Dopamine Inhibits Mammalian Photoreceptor Na+,K+-ATPase Activity via a Selective Effect on the [alpha]3 Isozyme. by Shulman LM, Fox DA.; 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38870
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Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells. by Knapp AG, Schmidt KF, Dowling JE.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53347
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Dopamine receptor binding in inbred mice: strain differences in mesolimbic and nigrostriatal dopamine binding sites. by Boehme RE, Ciaranello RD.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319540
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Dopamine receptor gene expression by enkephalin neurons in rat forebrain. by Le Moine C, Normand E, Guitteny AF, Fouque B, Teoule R, Bloch B.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53235
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Dopamine receptor regulating factor, DRRF: A zinc finger transcription factor. by Hwang CK, D'Souza UM, Eisch AJ, Yajima S, Lammers CH, Yang Y, Lee SH, Kim YM, Nestler EJ, Mouradian MM.; 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34707
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Dopamine receptor subtypes colocalize in rat striatonigral neurons. by Surmeier DJ, Eberwine J, Wilson CJ, Cao Y, Stefani A, Kitai ST.; 1992 Nov 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50301
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Dopamine receptor subtypes modulate olfactory bulb [gamma]-aminobutyric acid type A receptors. by Brunig I, Sommer M, Hatt H, Bormann J.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26806
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Dopamine receptor turnover rates in rat striatum are age-dependent. by Leff SE, Gariano R, Creese I.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345332
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Dopamine Receptors in the Substantia Nigra are Involved in the Regulation of Muscle Tone. by Double KL, Crocker AD.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42581
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Dopamine regulates expression of the glandular-type kallikrein gene at the transcriptional level in the pituitary. by Pritchett DB, Roberts JL.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298899
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Dopamine stimulates expression of the human immunodeficiency virus type 1 via NF-kappaB in cells of the immune system. by Rohr O, Sawaya BE, Lecestre D, Aunis D, Schaeffer E.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148562
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Dopamine Stimulation of Active Na and Cl Absorption in Rabbit Ileum INTERACTION WITH [alpha]2-ADRENERGIC AND SPECIFIC DOPAMINE RECEPTORS. by Donowitz M, Cusolito S, Battisti L, Fogel R, Sharp GW.; 1982 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370156
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Dopamine stimulation of phosphatidylcholine (lecithin) biosynthesis in rat brain neurons. by Leprohon CE, Blusztajn JK, Wurtman RJ.; 1983 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=393753
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Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex. by Goldman-Rakic PS, Leranth C, Williams SM, Mons N, Geffard M.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298423
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Dopamine tone regulates D1 receptor trafficking and delivery in striatal neurons in dopamine transporter-deficient mice. by Dumartin B, Jaber M, Gonon F, Caron MG, Giros B, Bloch B.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26530
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Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age. by Bannon MJ, Poosch MS, Xia Y, Goebel DJ, Cassin B, Kapatos G.; 1992 Aug 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49652
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Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. by Kitayama S, Shimada S, Xu H, Markham L, Donovan DM, Uhl GR.; 1992 Aug 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49795
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Dopamine Transporters are Markedly Reduced in Lesch-Nyhan Disease in vivo. by Wong DF, Harris JC, Naidu S, Yokoi F, Marenco S, Dannals RF, Ravert HT, Yaster M, Evans A, Rousset O, Bryan RN, Gjedde A, Kuhar MJ, Breese GR.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39282
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Dopamine turnover and glutathione oxidation: implications for Parkinson disease. by Spina MB, Cohen G.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286698
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Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments. by Graybiel AM, Moratalla R.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298424
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Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1. by Dong Z, Ferger B, Paterna JC, Vogel D, Furler S, Osinde M, Feldon J, Bueler H.; 2003 Oct 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=218776
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Dopamine-dependent responses to morphine depend on glucocorticoid receptors. by Marinelli M, Aouizerate B, Barrot M, Le Moal M, Piazza PV.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22744
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Dopamine-dependent synaptic plasticity in striatum during in vivo development. by Tang KC, Low MJ, Grandy DK, Lovinger DM.; 2001 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14741
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Dopamine-induced Exocytosis of Na,K-ATPase Is Dependent on Activation of Protein Kinase C-[epsilon] and -[delta]. by Ridge KM, Dada L, Lecuona E, Bertorello AM, Katz AI, Mochly-Rosen D, Sznajder JI.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102276
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Dopamine-induced recruitment of dopamine D1 receptors to the plasma membrane. by Brismar H, Asghar M, Carey RM, Greengard P, Aperia A.; 1998 May 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20419
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Dopaminergic control of 125I-labeled neurotensin binding site density in corticolimbic structures of the rat brain. by Herve D, Tassin JP, Studler JM, Dana C, Kitabgi P, Vincent JP, Glowinski J, Rostene W.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=386468
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Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary. by Onali P, Schwartz JP, Costa E.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349074
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Dopaminergic neurons from embryonic mouse mesencephalon are enriched in culture through immunoreaction with monoclonal antibody to neural specific protein 4 and flow cytometry. by di Porzio U, Rougon G, Novotny EA, Barker JL.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299287
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Dopaminergic neurons in the brain and dopaminergic innervation of the albumen gland in mated and virgin helisoma duryi (mollusca: pulmonata). by Kiehn L, Saleuddin S, Lange A.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37538
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Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. by Di Chiara G, Imperato A.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281732
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Effect of 6-Hydroxydopamine on Host Resistance against Listeria monocytogenes Infection. by Miura T, Kudo T, Matsuki A, Sekikawa K, Tagawa YI, Iwakura Y, Nakane A.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98806
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Effect of low-dose dopamine on the pharmacokinetics of tobramycin in dogs. by Kirby MG, Dasta JF, Armstrong DK, Tallman R Jr.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180388
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Effect of loxapine on peripheral dopamine-like and serotonin receptors in patients with schizophrenia. by Singh AN, Barlas C, Saeedi H, Mishra RK.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161724
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Effects of Central Cholinergic Blockade on Striatal Dopamine Release Measured with Positron Emission Tomography in Normal Human Subjects. by Dewey SL, Smith GS, Logan J, Brodie JD, Simkowitz P, MacGregor RR, Fowler JS, Volkow ND, Wolf AP.; 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48075
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Effects of Dietary Sodium and of Acute Saline Infusion on the Interrelationship between Dopamine Excretion and Adrenergic Activity in Man. by Alexander RW, Gill JR Jr, Yamabe H, Lovenberg W, Keiser HR.; 1974 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301540
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Effects of Metoclopramide and Bromocriptine on the Renin-Angiotensin-Aldosterone System in Man DOPAMINERGIC CONTROL OF ALDOSTERONE. by Carey RM, Thorner MO, Ortt EM.; 1979 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372008
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Effects of short-term administration of valproate on serotonin-1A and dopamine receptor function in healthy human subjects. by Delva NJ, Brooks DL, Franklin M, AlSaid K, Hawken ER, Merali Z, Lawson JS, Ravindran AV.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161716
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Efficacy of Low-Dose Dopamine in Preventing Amphotericin B Nephrotoxicity in Bone Marrow Transplant Patients and Leukemia Patients. by Camp MJ, Wingard JR, Gilmore CE, Lin LS, Dix SP, Davidson TG, Geller RB.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106006
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Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. by Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122367
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Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M4 muscarinic acetylcholine receptor knockout mice. by Gomeza J, Zhang L, Kostenis E, Felder C, Bymaster F, Brodkin J, Shannon H, Xia B, Deng CX, Wess J.; 1999 Aug 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17915
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Estrogen receptor-dependent sexual differentiation of dopaminergic neurons in the preoptic region of the mouse. by Simerly RB, Zee MC, Pendleton JW, Lubahn DB, Korach KS.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28435
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Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum. by Fuxe K, O'Connor WT, Antonelli T, Osborne PG, Tanganelli S, Agnati LF, Ungerstedt U.; 1992 Jun 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49338
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Evidence of positive selection acting at the human dopamine receptor D4 gene locus. by Ding YC, Chi HC, Grady DL, Morishima A, Kidd JR, Kidd KK, Flodman P, Spence MA, Schuck S, Swanson JM, Zhang YP, Moyzis RK.; 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117557
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Expression of a dopamine D2 receptor-activated K + channel on identified striatopallidal and striatonigral neurons. by Waszczak BL, Martin LP, Greif GJ, Freedman JE.; 1998 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21661
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Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia. by Weiner DM, Levey AI, Brann MR.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54680
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Expression of striatal D1 dopamine receptors coupled to inositol phosphate production and Ca2+ mobilization in Xenopus oocytes. by Mahan LC, Burch RM, Monsma FJ Jr, Sibley DR.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53653
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Extracellular Dopamine Concentration in the Retina of the Clawed Frog, Xenopus laevis. by Witkovsky P, Nicholson C, Rice ME, Bohmaker K, Meller E.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46782
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Feeding behavior in dopamine-deficient mice. by Szczypka MS, Rainey MA, Kim DS, Alaynick WA, Marck BT, Matsumoto AM, Palmiter RD.; 1999 Oct 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18425
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FnuD II RFLP at the human dopamine-[beta]-hydroxylase (D[beta]H) locus. by Perry SE, Phillips JA III, Robertson D.; 1991 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333814
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GABAergic synapses made by a retinal dopaminergic neuron. by Contini M, Raviola E.; 2003 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=298777
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Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease. by Xia XG, Harding T, Weller M, Bieneman A, Uney JB, Schulz JB.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56978
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Generation of an activating Zn2 + switch in the dopamine transporter: Mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle. by Loland CJ, Norregaard L, Litman T, Gether U.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122251
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Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. by Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa SI, Nakatsuji N, Sasai Y.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122233
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Genes for catecholamine biosynthesis: cloning by expression and identification of the cDNA for rat dopamine beta-hydroxylase. by O'Malley KL, Mauron A, Raese J, Barchas JD, Kedes L.; 1983 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=393777
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Genetic control of number of midbrain dopaminergic neurons in inbred strains of mice: relationship to size and neuronal density of the striatum. by Baker H, Joh TH, Reis DJ.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349836
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Glucocorticoids have State-Dependent Stimulant Effects on the Mesencephalic Dopaminergic Transmission. by Piazza PV, Rouge-Pont F, Deroche V, Maccari S, Simon H, Moal ML.; 1996 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38739
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Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. by Gainetdinov RR, Mohn AR, Bohn LM, Caron MG.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58681
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Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo. by Yamada M, Oligino T, Mata M, Goss JR, Glorioso JC, Fink DJ.; 1999 Mar 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22423
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High levels of a retinoic acid-generating dehydrogenase in the meso-telencephalic dopamine system. by McCaffery P, Drager UC.; 1994 Aug 2; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44484
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Horizontal cell gap junctions: single-channel conductance and modulation by dopamine. by McHahon DG, Knapp AG, Dowling JE.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298122
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Human dopamine beta-hydroxylase gene: two mRNA types having different 3'terminal regions are produced through alternative polyadenylation. by Kobayashi K, Kurosawa Y, Fujita K, Nagatsu T.; 1989 Feb 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331724
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Human striatal dopamine receptors are organized in compartments. by Joyce JN, Sapp DW, Marshall JF.; 1986 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=386853
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Hyperactivity and impaired response habituation in hyperdopaminergic mice. by Zhuang X, Oosting RS, Jones SR, Gainetdinov RR, Miller GW, Caron MG, Hen R.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29368
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Hyperactivity, elevated dopaminergic transmission, and response to amphetamine in M1 muscarinic acetylcholine receptor-deficient mice. by Gerber DJ, Sotnikova TD, Gainetdinov RR, Huang SY, Caron MG, Tonegawa S.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65026
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Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells. by Urena J, Fernandez-Chacon R, Benot AR, Alvarez de Toledo GA, Lopez-Barneo J.; 1994 Oct 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44987
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Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. by Levesque D, Diaz J, Pilon C, Martres MP, Giros B, Souil E, Schott D, Morgat JL, Schwartz JC, Sokoloff P.; 1992 Sep 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49875
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Immunohistochemical evidence for the existence of a dopamine- and cyclic AMPregulated phosphoprotein (DARPP-32) in brown adipose tissue of pigs. by Meister B, Fried G, Hokfelt T, Hemmings HC Jr, Greengard P.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282531
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Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus. by Huang Q, Zhou D, Chase K, Gusella JF, Aronin N, DiFiglia M.; 1992 Dec 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50683
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Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells. by Clarkson ED, Rosa FG, Edwards-Prasad J, Weiland DA, Witta SE, Freed CR, Prasad KN.; 1998 Feb 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18740
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Increased abundance of alternatively spliced forms of D2 dopamine receptor mRNA after denervation. by Neve KA, Neve RL, Fidel S, Janowsky A, Higgins GA.; 1991 Apr 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51327
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Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. by AbiDargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M.; 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16677
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Increased Dopamine Turnover in the Prefrontal Cortex Impairs Spatial Working Memory Performance in Rats and Monkeys. by Murphy BL, Arnsten AF, GoldmanRakic PS, Roth RH.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40079
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Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa. by Bordet R, Ridray S, Carboni S, Diaz J, Sokoloff P, Schwartz JC.; 1997 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20375
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Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor activation. by Chartoff EH, Marck BT, Matsumoto AM, Dorsa DM, Palmiter RD.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56981
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Inheritance of Low Immunoreactive Human Plasma Dopamine-[beta]-Hydroxylase RADIOIMMUNOASSAY STUDIES. by Dunnette J, Weinshilboum R.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372460
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Interaction of pergolide with central dopaminergic receptors. by Goldstein M, Lieberman A, Lew JY, Asano T, Rosenfeld MR, Makman MH.; 1980 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349691
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Interactions of GIPC with Dopamine D2, D3 but not D4 Receptors Define a Novel Mode of Regulation of G Protein-coupled Receptors. by Jeanneteau F, Diaz J, Sokoloff P, Griffon N.; 2004 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=329290
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Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease. by Bilang-Bleuel A, Revah F, Colin P, Locquet I, Robert JJ, Mallet J, Horellou P.; 1997 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23145
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Intravenous Cocaine, Morphine, and Amphetamine Preferentially Increase Extracellular Dopamine in the "Shell" as Compared with the "Core" of the Rat Nucleus Accumbens. by Pontieri FE, Tanda G, Chiara GD.; 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40345
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Isolated horizontal cells from carp retina demonstrate dopamine-dependent accumulation of cyclic AMP. by Van Buskirk R, Dowling JE.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349364
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Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. by Schuff KG, Hentges ST, Kelly MA, Binart N, Kelly PA, Iuvone PM, Asa SL, Low MJ.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151153
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Lazaroids Improve the Survival of Grafted Rat Embryonic Dopamine Neurons. by Nakao N, Frodl EM, Duan W, Widner H, Brundin P.; 1994 Dec 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45447
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Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. by Seeman P, Niznik HB, Guan HC, Booth G, Ulpian C.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298666
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Local circuit neurons in the striatum regulate neural and behavioral responses to dopaminergic stimulation. by Saka E, Iadarola M, Fitzgerald DJ, Graybiel AM.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124413
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Localization of D1 and D2 Dopamine Receptors in Brain with Subtype- Specific Antibodies. by Levey AI, Hersch SM, Rye DB, Sunahara RK, Niznik HB, Kitt CA, Price DL, Maggio R, Brann MR, Ciliax BJ.; 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47460
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Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission. by Fremeau RT Jr, Duncan GE, Fornaretto MG, Dearry A, Gingrich JA, Breese GR, Caron MG.; 1991 May 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51535
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Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain. by Murray AM, Ryoo HL, Gurevich E, Joyce JN.; 1994 Nov 8; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45209
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Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry. by Mengod G, Martinez-Mir MI, Vilaro MT, Palacios JM.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298322
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Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate-dopamine interactions. by Stinus L, Koob GF, Ling N, Bloom FE, Le Moal M.; 1980 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348707
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Loss of Central Nervous System Component of Dopaminergic Inhibition of Prolactin Secretion in Patients with Prolactin-Secreting Pituitary Tumors. by Fine SA, Frohman LA.; 1978 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372615
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Low Serum Dopamine [beta]-Hydroxylase Activity A MARKER OF CONGESTIVE HEART FAILURE. by Horwitz LD, Travis VL.; 1978 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371846
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Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. by Young WS 3rd, Bonner TI, Brann MR.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=387235
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Mesolimbic dopaminergic decline after cannabinoid withdrawal. by Diana M, Melis M, Muntoni AL, Gessa GL.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21497
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Midbrain injection of recombinant adeno-associated virus encoding rat glial cell linederived neurotrophic factor protects nigral neurons in a progressive 6hydroxydopamine-induced degeneration model of Parkinson's disease in rats. by Mandel RJ, Spratt SK, Snyder RO, Leff SE.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28436
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Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. by Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, Triarhou LC, Chernet E, Perry KW, Nelson DL, Luecke S, Phebus LA, Bymaster FP, Paul SM.; 2001 Dec 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64739
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Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. by Monsma FJ Jr, Mahan LC, McVittie LD, Gerfen CR, Sibley DR.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54609
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Molecular dynamics of dopamine at the D2 receptor. by Dahl SG, Edvardsen O, Sylte I.; 1991 Sep 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52456
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Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. by Sora I, Hall FS, Andrews AM, Itokawa M, Li XF, Wei HB, Wichems C, Lesch KP, Murphy DL, Uhl GR.; 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33204
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Morphogenic Potentials of D2, D3, and D4 Dopamine Receptors Revealed in Transfected Neuronal Cell Lines. by Swarzenski BC, Tang L, Oh YJ, O'Malley KL, Todd RD.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43006
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Mortality in 7B2 null mice can be rescued by adrenalectomy: Involvement of dopamine in ACTH hypersecretion. by Laurent V, Kimble A, Peng B, Zhu P, Pintar JE, Steiner DF, Lindberg I.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122477
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Most central nervous system D2 dopamine receptors are coupled to their effectors by Go. by Jiang M, Spicher K, Boulay G, Wang Y, Birnbaumer L.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30695
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Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes. by Grandy DK, Zhang YA, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O.; 1991 Oct 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52675
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Nerve Growth Factor in the Anterior Pituitary: Localization in Mammotroph Cells and Cosecretion with Prolactin by a Dopamine-Regulated Mechanism. by Missale C, Boroni F, Sigala S, Buriani A, Fabris M, Leon A, Toso RD, Spano P.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39519
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Neurally Mediated Increase in Dopamine-[beta]-Hydroxylase Activity. by Molinoff PB, Brimijoin S, Weinshilboum R, Axelrod J.; 1970 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283066
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Neuromodulatory Actions of Dopamine in the Neostriatum are Dependent Upon the Excitatory Amino Acid Receptor Subtypes Activated. by Cepeda C, Buchwald NA, Levine MS.; 1993 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47612
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Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. by Nass R, Hall DH, Miller DM III, Blakely RD.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122507
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Neurotransmitter interactions in psychotropic drug action: beyond dopamine and serotonin. by Greenshaw AJ.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165789
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Nitric Oxide Inhibits the Release of Norepinephrine and Dopamine From the Medial Basal Hypothalamus of the Rat. by Seilicovich A, Lasaga M, Befumo M, Duvilanski BH, Diaz MD, Rettori V, McCann SM.; 1995 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40619
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N-Terminal Phosphorylation of the Dopamine Transporter Is Required for Amphetamine-Induced Efflux. by Khoshbouei H, Sen N, Guptaroy B, Johnson L', Lund D, Gnegy ME, Galli A, Javitch JA.; 2004 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=368172
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Nuclear translocation of NF-[kappa]B is increased in dopaminergic neurons of patients with Parkinson disease. by Hunot S, Brugg B, Ricard D, Michel PP, Muriel MP, Ruberg M, Faucheux BA, Agid Y, Hirsch EC.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23856
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Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. by Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De Mayo F, Burbach JP, Conneely OM.; 1998 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19954
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Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. by Spanagel R, Herz A, Shippenberg TS.; 1992 Mar 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48593
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Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. by Javitch JA, D'Amato RJ, Strittmatter SM, Snyder SH.; 1985 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=397515
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Personality traits and brain dopaminergic function in Parkinson's disease. by Kaasinen V, Nurmi E, Bergman J, Eskola O, Solin O, Sonninen P, Rinne JO.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60860
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Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene. by Le Moine C, Normand E, Bloch B.; 1991 May 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51627
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Phosphatidylinositol 3-Kinase-mediated Endocytosis of Renal Na +,K +-ATPase [alpha] Subunit in Response to Dopamine. by Chibalin AV, Zierath JR, Katz AI, Berggren PO, Bertorello AM.; 1998 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25342
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Phosphorylated Mr 32,000 dopamine- and cAMP-regulated phosphoprotein inhibits Na+,K(+)-ATPase activity in renal tubule cells. by Aperia A, Fryckstedt J, Svensson L, Hemmings HC Jr, Nairn AC, Greengard P.; 1991 Apr 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51326
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Pitx3 is required for development of substantia nigra dopaminergic neurons. by Nunes I, Tovmasian LT, Silva RM, Burke RE, Goff SP.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153078
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Point mutant mice with hypersensitive [alpha]4 nicotinic receptors show dopaminergic deficits and increased anxiety. by Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak MW, Fonck C, Nashmi R, Kofuji P, Dang H, Shi W, Fidan M, Khakh BS, Chen Z, Bowers BJ, Boulter J, Wehner JM, Lester HA.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30217
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Profound Decrement of Mesolimbic Dopaminergic Neuronal Activity During Ethanol Withdrawal Syndrome in Rats: Electrophysiological and Biochemical Evidence. by Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL.; 1993 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47268
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Profound neuronal plasticity in response to inactivation of the dopamine transporter. by Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG.; 1998 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19957
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Progesterone receptor and dopamine receptors are required in [Delta]9tetrahydrocannabinol modulation of sexual receptivity in female rats. by Mani SK, Mitchell A, O'Malley BW.; 2001 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14740
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Prominence of the dopamine D2 short isoform in dopaminergic pathways. by Khan ZU, Mrzljak L, Gutierrez A, de la Calle A, Goldman-Rakic PS.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22740
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Promotion of central cholinergic and dopaminergic neuron differentiation by brainderived neurotrophic factor but not neurotrophin 3. by Knusel B, Winslow JW, Rosenthal A, Burton LE, Seid DP, Nikolics K, Hefti F.; 1991 Feb 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50934
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Quantitative determination of dopamine receptor subtypes not linked to activation of adenylate cyclase in rat striatum. by Huff RM, Molinoff PB.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347380
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Regulation of dopamine- and adenosine-dependent adenylate cyclase systems of chicken embryo retina cells in culture. by de Mello MC, Ventura AL, Paes de Carvalho R, Klein WL, de Mello FG.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346974
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Regulation of dopaminergic pathways by retinoids: Activation of the D2 receptor promoter by members of the retinoic acid receptor --retinoid X receptor family. by Samad TA, Krezel W, Chambon P, Borrelli E.; 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24972
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Regulation of recombinant rat tyrosine hydroxylase by dopamine. by Ribeiro P, Wang Y, Citron BA, Kaufman S.; 1992 Oct 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50178
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Regulation of Striatal D1A Dopamine Receptor Gene Transcription by Brn-4. by Okazawa H, Imafuku I, Minowa MT, Kanazawa I, Hamada H, Mouradian MM.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38161
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Regulation of the phosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa in vivo by dopamine D1, dopamine D2, and adenosine A2A receptors. by Svenningsson P, Lindskog M, Ledent C, Parmentier M, Greengard P, Fredholm BB, Fisone G.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26526
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Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds. by Chen CL, Dionne FT, Roberts JL.; 1983 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=393788
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Relationship between Psychostimulant-Induced ``High" and Dopamine Transporter Occupancy. by Volkow ND, Wang G, Fowler JS, Gatley SJ, Ding Y, Logan J, Dewey SL, Hitzemann R, Lieberman J.; 1996 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38394
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RELEASE OF NEWLY SYNTHESIZED DOPAMINE FROM DOPAMINECONTAINING TERMINALS IN THE STRIATUM OF THE RAT. by Besson MJ, Cheramy A, Feltz P, Glowinski J.; 1969 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=223661
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Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions. by List SJ, Seeman P.; 1981 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319401
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Responses of Saphenous and Mesenteric Veins to Administration of Dopamine. by Mark AL, Iizuka T, Wendling MG, Eckstein JW.; 1970 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322468
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Retinal dopamine and form-deprivation myopia. by Stone RA, Lin T, Laties AM, Iuvone PM.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286542
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Retinal horizontal cell gap junctional conductance is modulated by dopamine through a cyclic AMP-dependent protein kinase. by Lasater EM.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299284
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Retroviral transfer of a human tyrosine hydroxylase cDNA in various cell lines: regulated release of dopamine in mouse anterior pituitary AtT-20 cells. by Horellou P, Guibert B, Leviel V, Mallet J.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298031
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RFLP for human DBH (dopamine beta-hydroxylase). by Schuback DE, Ozelius L, Hu G, Craft CM, Raese J, Breakefield XO, Hsu YP.; 1990 Jan 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330306
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Role of Neuronal Nitric Oxide in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Dopaminergic Neurotoxicity. by Przedborski S, Jackson-Lewis V, Yokoyama R, Shibata T, Dawson VL, Dawson TM.; 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39317
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Role of Oxidation in the Neurotoxic Effects of Intrastriatal Dopamine Injections. by Hastings TG, Lewis DA, Zigmond MJ.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39890
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Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method. by Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D.; 1997 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20129
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Schizophrenia: More dopamine, more D2 receptors. by Seeman P, Kapur S.; 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33999
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Selective Induction by Nerve Growth Factor of Tyrosine Hydroxylase and Dopamine[beta]-Hydroxylase in the Rat Superior Cervical Ganglia. by Thoenen H, Angeletti PU, Levi-Montalcini R, Kettler R.; 1971 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=389249
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Selective Loss of Dopamine D3-Type Receptor mRNA Expression In Parietal and Motor Cortices of Patients with Chronic Schizophrenia. by Schmauss C, Haroutunian V, Davis KL, Davidson M.; 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47477
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Selective loss of dopaminergic nigro-striatal neurons in brains of Atm-deficient mice. by Eilam R, Peter Y, Elson A, Rotman G, Shiloh Y, Groner Y, Segal M.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22886
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Selective modulation of excitatory and inhibitory microcircuits by dopamine. by Gao WJ, Goldman-Rakic PS.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151427
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Selective up-regulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation. by Scott L, Kruse MS, Forssberg H, Brismar H, Greengard P, Aperia A.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122247
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Selective Vulnerability of Late-Generated Dopaminergic Neurons of the Substantia Nigra in Weaver Mutant Mice. by Bayer SA, Wills KV, Triarhou LC, Verina T, Thomas JD, Ghetti B.; 1995 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40939
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Sequence tagged site (STS) TaqI RFLP at dopamine beta-hydroxylase (DBH). by Gelernter J, Gejman PV, Bisighini S, Kidd KK.; 1991 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=328142
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Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. by Bibb JA, Yan Z, Svenningsson P, Snyder GL, Pieribone VA, Horiuchi A, Nairn AC, Messer A, Greengard P.; 2000 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18747
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Single K+ channels activated by D2 dopamine receptors in acutely dissociated neurons from rat corpus striatum. by Freedman JE, Weight FF.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280265
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Single Photon Emission Computed Tomographic Imaging Demonstrates Loss of Striatal Dopamine Transporters in Parkinson Disease. by Innis RB, Seibyl JP, Scanley BE, Laruelle M, Abi-Dargham A, Wallace E, Baldwin RM, Zea-Ponce Y, Zoghbi S, Wang S, Gao Y, Neumeyer JL, Charney DS, Hoffer PB, Marek KL.; 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48106
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Single Photon Emission Computerized Tomography Imaging of AmphetamineInduced Dopamine Release in Drug-Free Schizophrenic Subjects. by Laruelle M, AbiDargham A, Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB.; 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38625
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Single-channel properties of the nonselective cation conductance induced by neurotensin in dopaminergic neurons. by Chien PY, Farkas RH, Nakajima S, Nakajima Y.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26237
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Sleep attacks in patients taking dopamine agonists: review. by Homann CN, Wenzel K, Suppan K, Ivanic G, Kriechbaum N, Crevenna R, Ott E.; 2002 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116443
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Sodium ion modulates D2 receptor characteristics of dopamine agonist and antagonist binding sites in striatum and retina. by Makman MH, Dvorkin B, Klein PN.; 1982 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346608
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Specific modulation of dopamine expression in neuronal hybrid cells by primary cells from different brain regions. by Choi HK, Won L, Roback JD, Wainer BH, Heller A.; 1992 Oct 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50040
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Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. by Ferre S, von Euler G, Johansson B, Fredholm BB, Fuxe K.; 1991 Aug 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52269
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Stimulation of protein-tyrosine phosphorylation in rat striatum after lesion of dopamine neurons or chronic neuroleptic treatment. by Girault JA, Siciliano JC, Robel L, Herve D.; 1992 Apr 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48744
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Stimulation of the carotid chemoreceptors of the dog by dopamine. by Jacobs L, Comroe JH Jr.; 1968 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=224850
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Striatal Fos Expression is Indicative of Dopamine D1/D2 Synergism and Receptor Supersensitivity. by LaHoste GJ, Yu J, Marshall JF.; 1993 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47159
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Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. by Farde L, Ehrin E, Eriksson L, Greitz T, Hall H, Hedstrom CG, Litton JE, Sedvall G.; 1985 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=397888
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Suppression of glucocorticoid secretion and antipsychotic drugs have similar effects on the mesolimbic dopaminergic transmission. by Piazza PV, Barrot M, Rouge-Pont F, Marinelli M, Maccari S, Abrous DN, Simon H, Le Moal M.; 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26424
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Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons. by Cyr M, Beaulieu JM, Laakso A, Sotnikova TD, Yao WD, Bohn LM, Gainetdinov RR, Caron MG.; 2003 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=196922
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Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment. by Hastrup H, Karlin A, Javitch JA.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56914
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Sympathetic Nerve Cell Destruction in Newborn Mammals by 6-Hydroxydopamine. by Angeletti PU, Levi-Montalcini R.; 1970 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286199
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Target neuron-specific process formation by embryonic mesencephalic dopamine neurons in vitro. by Hemmendinger LM, Garber BB, Hoffmann PC, Heller A.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319989
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The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets. by Cheung PY, Barrington KJ.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31580
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The Effects of Dopamine D1 Receptor Blockade in the Prelimbic --Infralimbic Areas on Behavioral Flexibility. by Ragozzino ME.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155930
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The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice. by Chen JF, Moratalla R, Impagnatiello F, Grandy DK, Cuellar B, Rubinstein M, Beilstein MA, Hackett E, Fink JS, Low MJ, Ongini E, Schwarzschild MA.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29366
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Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways. by Engler D, Chad D, Jackson IM.; 1982 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370204
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Transcription mediated by a cAMP-responsive promoter element is reduced upon activation of dopamine D2 receptors. by Montmayeur JP, Borrelli E.; 1991 Apr 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51400
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Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine neurotoxicity. by Offen D, Beart PM, Cheung NS, Pascoe CJ, Hochman A, Gorodin S, Melamed E, Bernard R, Bernard O.; 1998 May 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20458
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Transplantation of ventral mesencephalic anlagen to hosts with genetic nigrostriatal dopamine deficiency. by Triarhou LC, Low WC, Ghetti B.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=387017
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Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription. by Liss B, Franz O, Sewing S, Bruns R, Neuhoff H, Roeper J.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125678
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Tyrosine administration increases striatal dopamine release in rats with partial nigrostriatal lesions. by Melamed E, Hefti F, Wurtman RJ.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349822
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Variability of Dopamine D4 Receptor (DRD4) Gene Sequence Within and Among Nonhuman Primate Species. by Livak KJ, Rogers J, Lichter JB.; 1995 Jan 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42753
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Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons. by Sawamoto K, Nakao N, Kobayashi K, Matsushita N, Takahashi H, Kakishita K, Yamamoto A, Yoshizaki T, Terashima T, Murakami F, Itakura T, Okano H.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33484
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Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson's disease? by Freed CR.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122265
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with dopamine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “dopamine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for dopamine (hyperlinks lead to article summaries): •
A case of dopamine agonists inhibiting pancreatic polypeptide secretion from an islet cell tumor. Author(s): Pathak RD, Tran TH, Burshell AL. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 February; 89(2): 581-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764765
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A dopamine D2 receptor gene polymorphism and physical activity in two family studies. Author(s): Simonen RL, Rankinen T, Perusse L, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Source: Physiology & Behavior. 2003 April; 78(4-5): 751-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782232
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A family-based association study of attention-deficit hyperactivity disorder and dopamine D2 receptor TaqI A alleles. Author(s): Huang YS, Lin SK, Wu YY, Chao CC, Chen CK. Source: Chang Gung Med J. 2003 December; 26(12): 897-903. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008324
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A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease. Author(s): Healy DG, Abou-Sleiman PM, Ozawa T, Lees AJ, Bhatia K, Ahmadi KR, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Barrone P, Tolosa E, Quinn N, Goldstein DB, Wood NW. Source: Annals of Neurology. 2004 March; 55(3): 443-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991826
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A genetic association study of migraine with dopamine receptor 4, dopamine transporter and dopamine-beta-hydroxylase genes. Author(s): Mochi M, Cevoli S, Cortelli P, Pierangeli G, Soriani S, Scapoli C, Montagna P. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 February; 23(6): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624717
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A model of dopamine modulated cortical activation. Author(s): Ashby FG, Casale MB. Source: Neural Networks : the Official Journal of the International Neural Network Society. 2003 September; 16(7): 973-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692632
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Aberrant D1 and D3 dopamine receptor transregulation in hypertension. Author(s): Zeng C, Wang D, Asico LD, Welch WJ, Wilcox CS, Hopfer U, Eisner GM, Felder RA, Jose PA. Source: Hypertension. 2004 March; 43(3): 654-60. Epub 2004 January 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732731
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ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow. Author(s): Lou HC, Rosa P, Pryds O, Karrebaek H, Lunding J, Cumming P, Gjedde A. Source: Developmental Medicine and Child Neurology. 2004 March; 46(3): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14995087
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Alcohol promotes dopamine release in the human nucleus accumbens. Author(s): Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A. Source: Synapse (New York, N.Y.). 2003 September 15; 49(4): 226-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827641
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ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia. Author(s): Galter D, Buervenich S, Carmine A, Anvret M, Olson L. Source: Neurobiology of Disease. 2003 December; 14(3): 637-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678778
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Allelic variants interaction of dopamine receptor D4 polymorphism correlate with personality traits in young Korean female population. Author(s): Lee HJ, Lee HS, Kim YK, Kim SH, Kim L, Lee MS, Joe SH, Jung IK, Suh KY, Kim S. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 76-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627471
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alpha-Synuclein selectively increases manganese-induced viability loss in SK-N-MC neuroblastoma cells expressing the human dopamine transporter. Author(s): Pifl C, Khorchide M, Kattinger A, Reither H, Hardy J, Hornykiewicz O. Source: Neuroscience Letters. 2004 January 2; 354(1): 34-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698476
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Anatomical substrates for glutamate-dopamine interactions: evidence for specificity of connections and extrasynaptic actions. Author(s): Sesack SR, Carr DB, Omelchenko N, Pinto A. Source: Annals of the New York Academy of Sciences. 2003 November; 1003: 36-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684434
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Antioxidants inhibit the human cortical neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42. Author(s): Medina S, Martinez M, Hernanz A. Source: Free Radical Research. 2002 November; 36(11): 1179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592670
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Aripiprazole: a partial dopamine D2 receptor agonist antipsychotic. Author(s): Keck PE Jr, McElroy SL. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 655-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665420
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Association analysis for dopamine D3 receptor, dopamine D4 receptor and dopamine transporter genetic polymorphisms and P300 event-related potentials for normal young females. Author(s): Tsai SJ, Yu YW, Chen TJ, Chen MC, Hong CJ. Source: Psychiatric Genetics. 2003 March; 13(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605102
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Association between polymorphism of the dopamine transporter gene and early smoking onset: an interaction risk on nicotine dependence. Author(s): Ling D, Niu T, Feng Y, Xing H, Xu X. Source: Journal of Human Genetics. 2004; 49(1): 35-9. Epub 2003 December 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685824
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Association of the dopamine D4 receptor gene 7-repeat allele with neuropsychological test performance of children with ADHD. Author(s): Langley K, Marshall L, van den Bree M, Thomas H, Owen M, O'Donovan M, Thapar A. Source: The American Journal of Psychiatry. 2004 January; 161(1): 133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702261
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Association study of the dopamine and serotonin transporter genetic polymorphisms and methamphetamine abuse in Chinese males. Author(s): Hong CJ, Cheng CY, Shu LR, Yang CY, Tsai SJ. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 April; 110(4): 34551. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658362
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Attenuation of dopamine transporter activity by alpha-synuclein. Author(s): Wersinger C, Sidhu A. Source: Neuroscience Letters. 2003 April 17; 340(3): 189-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672538
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Bad medicine: low-dose dopamine in the ICU. Author(s): Holmes CL, Walley KR. Source: Chest. 2003 April; 123(4): 1266-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684320
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Bedtime cabergoline in Parkinson's disease patients with excessive daytime sleepiness induced by dopamine agonists. Author(s): Del Dotto P, Gambaccini G, Caneparo D, Berti C, Bernardini S, Bonuccelli U. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 October; 24(3): 170-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598071
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Behavioral improvement and dopamine release in a Parkinsonian rat model. Author(s): Gerin C. Source: Neuroscience Letters. 2002 September 13; 330(1): 5-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12213621
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Benzamide bioisosteres incorporating dihydroheteroazole substructures: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179). Author(s): Einsiedel J, Hubner H, Gmeiner P. Source: Bioorganic & Medicinal Chemistry Letters. 2001 September 17; 11(18): 2533-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549463
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Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter. Author(s): Houlihan WJ, Ahmad UF, Koletar J, Kelly L, Brand L, Kopajtic TA. Source: Journal of Medicinal Chemistry. 2002 September 12; 45(19): 4110-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12213054
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Best evidence in anesthetic practice. Prevention: dopamine does not prevent death, acute renal failure, or need for dialysis. Author(s): Bracco D, Parlow JL. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 April; 49(4): 417-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927484
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Bi-directional effects of GABA(B) receptor agonists on the mesolimbic dopamine system. Author(s): Cruz HG, Ivanova T, Lunn ML, Stoffel M, Slesinger PA, Luscher C. Source: Nature Neuroscience. 2004 February; 7(2): 153-9. Epub 2004 January 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745451
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Binding of cocaine-like radioligands to the dopamine transporter at 37 degrees C: effect of Na+ and substrates. Author(s): Wang LC, Cui XN, Chen N, Reith ME. Source: Journal of Neuroscience Methods. 2003 December 30; 131(1-2): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659820
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Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover. Author(s): de la Fuente-Fernandez R, Lu JQ, Sossi V, Jivan S, Schulzer M, Holden JE, Lee CS, Ruth TJ, Calne DB, Stoessl AJ. Source: Annals of Neurology. 2001 March; 49(3): 298-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261503
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Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease. Author(s): Nakamura T, Dhawan V, Chaly T, Fukuda M, Ma Y, Breeze R, Greene P, Fahn S, Freed C, Eidelberg D. Source: Annals of Neurology. 2001 August; 50(2): 181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11506400
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Blue cone electroretinogram amplitudes are related to dopamine function in cocainedependent patients. Author(s): Roy A, Roy M, Berman J, Gonzalez B. Source: Psychiatry Research. 2003 February 15; 117(2): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606020
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BP 897, a selective dopamine D3 receptor ligand with therapeutic potential for the treatment of cocaine-addiction. Author(s): Garcia-Ladona FJ, Cox BF. Source: Cns Drug Rev. 2003 Summer; 9(2): 141-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847556
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Brain dopamine is associated with eating behaviors in humans. Author(s): Volkow ND, Wang GJ, Maynard L, Jayne M, Fowler JS, Zhu W, Logan J, Gatley SJ, Ding YS, Wong C, Pappas N. Source: The International Journal of Eating Disorders. 2003 March; 33(2): 136-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616579
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Brain dopamine-stimulated adenylyl cyclase activity in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Author(s): Tong J, Fitzmaurice PS, Ang LC, Furukawa Y, Guttman M, Kish SJ. Source: Annals of Neurology. 2004 January; 55(1): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705122
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Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. Author(s): Morrish PK. Source: Jama : the Journal of the American Medical Association. 2002 July 17; 288(3): 312; Author Reply 312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117387
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Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. Author(s): Albin RL, Nichols TE, Frey KA. Source: Jama : the Journal of the American Medical Association. 2002 July 17; 288(3): 311-2; Author Reply 312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117386
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Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. Author(s): Ahlskog JE, Maraganore DM, Uitti RJ, Uhl GR. Source: Jama : the Journal of the American Medical Association. 2002 July 17; 288(3): 311; Author Reply 312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117385
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Brain oscillations, medium spiny neurons, and dopamine. Author(s): Murer MG, Tseng KY, Kasanetz F, Belluscio M, Riquelme LA. Source: Cellular and Molecular Neurobiology. 2002 December; 22(5-6): 611-32. Review. Erratum In: Cell Mol Neurobiol. 2003 June; 23(3): 449. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12585682
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Brain-derived neurotrophic factor and the plasticity of the mesolimbic dopamine pathway. Author(s): Guillin O, Griffon N, Diaz J, Le Foll B, Bezard E, Gross C, Lammers C, Stark H, Carroll P, Schwartz JC, Sokoloff P. Source: Int Rev Neurobiol. 2004; 59: 425-44. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006497
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Bupropion occupancy of the dopamine transporter is low during clinical treatment. Author(s): Meyer JH, Goulding VS, Wilson AA, Hussey D, Christensen BK, Houle S. Source: Psychopharmacology. 2002 August; 163(1): 102-5. Epub 2002 July 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185406
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Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Author(s): Volkow ND, Wang GJ, Fowler JS, Molina PE, Logan J, Gatley SJ, Gifford A, Ding YS, Wong C, Pappas NR, Zhu W, Swanson JM. Source: Psychopharmacology. 2003 March; 166(3): 264-70. Epub 2003 February 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589522
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Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. Author(s): Akil M, Kolachana BS, Rothmond DA, Hyde TM, Weinberger DR, Kleinman JE. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 March 15; 23(6): 2008-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657658
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Cellular and behavioral effects of D2 dopamine receptor hydrophobic eigenmodetargeted peptide ligands. Author(s): Mandell AJ, Selz KA, Owens MJ, Kinkead B, Shlesinger MF, Gutman DA, Arguragi V. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28 Suppl 1: S98-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827150
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Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough. Author(s): Lang AE, Obeso JA. Source: Lancet. Neurology. 2004 May; 3(5): 309-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15099546
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Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration. Author(s): Kugaya A, Seneca NM, Snyder PJ, Williams SA, Malison RT, Baldwin RM, Seibyl JP, Innis RB. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 February; 28(2): 413-20. Epub 2002 July 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589396
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Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications. Author(s): Calon F, Morissette M, Rajput AH, Hornykiewicz O, Bedard PJ, Di Paolo T. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 March; 18(3): 241-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621627
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Characterization of dopamine D2 receptor gene expression and binding sites in human placenta amniotic epithelial cells. Author(s): Elwan MA, Ishii T, Sakuragawa N. Source: Placenta. 2003 July; 24(6): 658-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828924
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Childhood inattention and dysphoria and adult obesity associated with the dopamine D4 receptor gene in overeating women with seasonal affective disorder. Author(s): Levitan RD, Masellis M, Lam RW, Muglia P, Basile VS, Jain U, Kaplan AS, Tharmalingam S, Kennedy SH, Kennedy JL. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 January; 29(1): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560322
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CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors. Author(s): Griffon N, Jeanneteau F, Prieur F, Diaz J, Sokoloff P. Source: Brain Research. Molecular Brain Research. 2003 September 10; 117(1): 47-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499480
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CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson's disease. Author(s): Zhu BT. Source: International Journal of Molecular Medicine. 2004 March; 13(3): 343-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767563
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Cognition following bilateral implants of embryonic dopamine neurons in PD: a double blind study. Author(s): Trott CT, Fahn S, Greene P, Dillon S, Winfield H, Winfield L, Kao R, Eidelberg D, Freed CR, Breeze RE, Stern Y. Source: Neurology. 2003 June 24; 60(12): 1938-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821736
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Cognitive effects of the dopamine receptor agonist pergolide. Author(s): Kimberg DY, D'Esposito M. Source: Neuropsychologia. 2003; 41(8): 1020-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667537
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Comparison of the discriminative-stimulus effects of SKF 38393 with those of other dopamine receptor agonists. Author(s): Desai RI, Terry P, Katz JL. Source: Behavioural Pharmacology. 2003 May; 14(3): 223-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799524
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Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry? Author(s): Lawrence AD, Evans AH, Lees AJ. Source: Lancet. Neurology. 2003 October; 2(10): 595-604. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505581
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Conditional ablation of striatal neuronal types containing dopamine D2 receptor disturbs coordination of basal ganglia function. Author(s): Sano H, Yasoshima Y, Matsushita N, Kaneko T, Kohno K, Pastan I, Kobayashi K. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 October 8; 23(27): 9078-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534241
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Constitutive oligomerization of human D2 dopamine receptors expressed in Spodoptera frugiperda 9 (Sf9) and in HEK293 cells. Analysis using coimmunoprecipitation and time-resolved fluorescence resonance energy transfer. Author(s): Gazi L, Lopez-Gimenez JF, Rudiger MP, Strange PG. Source: European Journal of Biochemistry / Febs. 2003 October; 270(19): 3928-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511374
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Conversion from dopamine agonists to pramipexole. An open-label trial in 227 patients with advanced Parkinson's disease. Author(s): Linazasoro G; Spanish Dopamine Agonists Study Group. Source: Journal of Neurology. 2004 March; 251(3): 335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15015015
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Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it? Author(s): Pirker W. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 October; 18 Suppl 7: S43-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531046
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Cyclic amidines as benzamide bioisosteres: EPC synthesis and SAR studies leading to the selective dopamine D4 receptor agonist FAUC 312. Author(s): Einsiedel J, Hubner H, Gmeiner P. Source: Bioorganic & Medicinal Chemistry Letters. 2003 March 10; 13(5): 851-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617906
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Cytokine suppression of dopamine-beta-hydroxylase by extracellular signalregulated kinase-dependent and -independent pathways. Author(s): Dziennis S, Habecker BA. Source: The Journal of Biological Chemistry. 2003 May 2; 278(18): 15897-904. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12609984
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DBH gene variants that cause low plasma dopamine beta hydroxylase with or without a severe orthostatic syndrome. Author(s): Deinum J, Steenbergen-Spanjers GC, Jansen M, Boomsma F, Lenders JW, van Ittersum FJ, Huck N, van den Heuvel LP, Wevers RA. Source: Journal of Medical Genetics. 2004 April; 41(4): E38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15060114
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Decreased striatal dopamine transporter binding in a patient with extrapontine myelinolysis. Author(s): Kim JS, Lee KS, Han SR, Chung YA. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 March; 18(3): 342-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621642
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Direct comparison of cerebrovascular effects of norepinephrine and dopamine in head-injured patients. Author(s): Steiner LA, Johnston AJ, Czosnyka M, Chatfield DA, Salvador R, Coles JP, Gupta AK, Pickard JD, Menon DK. Source: Critical Care Medicine. 2004 April; 32(4): 1049-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15071400
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Dopamine agonist therapy for hyperprolactinemia. Author(s): Bankowski BJ, Zacur HA. Source: Clinical Obstetrics and Gynecology. 2003 June; 46(2): 349-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808385
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Dopamine agonists and Parkinson's disease progression: what can we learn from neuroimaging studies. Author(s): Marek K, Jennings D, Seibyl J. Source: Annals of Neurology. 2003; 53 Suppl 3: S160-6; Discussion S166-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666107
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Dopamine agonists for cocaine dependence. Author(s): Soares BG, Lima MS, Reisser AA, Farrell M. Source: Cochrane Database Syst Rev. 2003; (2): Cd003352. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804461
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Dopamine and retinal function. Author(s): Witkovsky P. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 2004 January; 108(1): 17-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104164
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Dopamine D2 (DAD2) and dopamine D3 (DAD3) receptor gene polymorphisms and treatment outcome in alcohol dependence. Author(s): Wiesbeck GA, Weijers HG, Wodarz N, Herrmann MJ, Johann M, Keller HK, Michel TM, Boning J. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 July; 110(7): 81320. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811641
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Dopamine D4 ligands and models of receptor activation: 2-(4-pyridin-2-ylpiperazin-1ylmethyl)-1H-benzimidazole and related heteroarylmethylarylpiperazines exhibit a substituent effect responsible for additional efficacy tuning. Author(s): Stewart AO, Cowart MD, Moreland RB, Latshaw SP, Matulenko MA, Bhatia PA, Wang X, Daanen JF, Nelson SL, Terranova MA, Namovic MT, Donnelly-Roberts DL, Miller LN, Nakane M, Sullivan JP, Brioni JD. Source: Journal of Medicinal Chemistry. 2004 April 22; 47(9): 2348-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15084133
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Dopamine D4 receptor gene (DRD4) variants and schizophrenia: meta-analyses. Author(s): Jonsson EG, Sedvall GC, Nothen MM, Cichon S. Source: Schizophrenia Research. 2003 May 1; 61(1): 111-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648742
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Dopamine inhibits cytokine release and expression of tyrosine kinases, Lck and Fyn in activated T cells. Author(s): Ghosh MC, Mondal AC, Basu S, Banerjee S, Majumder J, Bhattacharya D, Dasgupta PS. Source: International Immunopharmacology. 2003 July; 3(7): 1019-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810359
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Dopamine receptor expression and function in clinically nonfunctioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. Author(s): Pivonello R, Matrone C, Filippella M, Cavallo LM, Di Somma C, Cappabianca P, Colao A, Annunziato L, Lombardi G. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 April; 89(4): 167483. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15070930
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Dopamine receptor hetero-oligomerization: a hypothesis for behavioral sensitization to psychostimulants. Author(s): Tsai SJ, Hong CJ. Source: Medical Hypotheses. 2003 July; 61(1): 18-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12781635
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Dopamine receptors and transporters in the brain reward circuits of type 1 and 2 alcoholics measured with human whole hemisphere autoradiography. Author(s): Tupala E, Hall H, Mantere T, Rasanen P, Sarkioja T, Tiihonen J. Source: Neuroimage. 2003 May; 19(1): 145-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12781734
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Dopamine stabilizes milrinone-induced changes in heart rate and arterial pressure during anaesthesia with isoflurane. Author(s): Karasawa F, Okuda T, Tsutsui M, Matsuoka N, Yamada S, Kawatani Y, Satoh T. Source: European Journal of Anaesthesiology. 2003 February; 20(2): 120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622495
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Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: a pilot study. Author(s): Rohde LA, Roman T, Szobot C, Cunha RD, Hutz MH, Biederman J. Source: Synapse (New York, N.Y.). 2003 May; 48(2): 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619042
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Dopamine transporter-mediated cytotoxicity of beta-carbolinium derivatives related to Parkinson's disease: relationship to transporter-dependent uptake. Author(s): Storch A, Hwang YI, Gearhart DA, Beach JW, Neafsey EJ, Collins MA, Schwarz J. Source: Journal of Neurochemistry. 2004 May; 89(3): 685-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086525
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Dopamine-dependent cytotoxicity of tetrahydrobiopterin: a possible mechanism for selective neurodegeneration in Parkinson's disease. Author(s): Choi HJ, Kim SW, Lee SY, Hwang O. Source: Journal of Neurochemistry. 2003 July; 86(1): 143-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807434
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Dopaminergic mouse mutants: investigating the roles of the different dopamine receptor subtypes and the dopamine transporter. Author(s): Tan S, Hermann B, Borrelli E. Source: Int Rev Neurobiol. 2003; 54: 145-97. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12785287
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Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects. Author(s): Robeson W, Dhawan V, Belakhlef A, Ma Y, Pillai V, Chaly T, Margouleff C, Bjelke D, Eidelberg D. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 June; 44(6): 961-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791826
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Early clinical investigation of Viozan (sibenadet HCl), a novel D2 dopamine receptor, beta2-adrenoceptor agonist for the treatment of chronic obstructive pulmonary disease symptoms. Author(s): Ind PW, Laitinen L, Laursen L, Wenzel S, Wouters E, Deamer L, Nystrom P. Source: Respiratory Medicine. 2003 January; 97 Suppl A: S9-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564607
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Early-onset schizophrenia and dopamine-related gene polymorphism. Author(s): Iwata Y, Matsumoto H, Minabe Y, Osada N, Nakamura K, Sekizawa T, Suzuki K, Sekine Y, Takei N, Mori N. Source: American Journal of Medical Genetics. 2003 January 1; 116B(1): 23-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12497608
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Eating disorders with binge-eating behaviour are associated with the s allele of the 3'UTR VNTR polymorphism of the dopamine transporter gene. Author(s): Shinohara M, Mizushima H, Hirano M, Shioe K, Nakazawa M, Hiejima Y, Ono Y, Kanba S. Source: Journal of Psychiatry & Neuroscience : Jpn. 2004 March; 29(2): 134-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15069467
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Effect of loxapine on peripheral dopamine-like and serotonin receptors in patients with schizophrenia. Author(s): Singh AN, Barlas C, Saeedi H, Mishra RK. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 January; 28(1): 39-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587849
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Effects of benserazide on L-DOPA-derived extracellular dopamine levels and aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopaminelesioned rats. Author(s): Shen H, Kannari K, Yamato H, Arai A, Matsunaga M. Source: The Tohoku Journal of Experimental Medicine. 2003 March; 199(3): 149-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12703659
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Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial. Author(s): Lerman C, Shields PG, Wileyto EP, Audrain J, Hawk LH Jr, Pinto A, Kucharski S, Krishnan S, Niaura R, Epstein LH. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2003 September; 22(5): 541-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570538
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Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Author(s): De Backer D, Creteur J, Silva E, Vincent JL. Source: Critical Care Medicine. 2003 June; 31(6): 1659-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794401
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Effects of short-term administration of valproate on serotonin-1A and dopamine receptor function in healthy human subjects. Author(s): Delva NJ, Brooks DL, Franklin M, al-Said K, Hawken ER, Merali Z, Lawson JS, Ravindran AV. Source: Journal of Psychiatry & Neuroscience : Jpn. 2002 November; 27(6): 429-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12491576
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Efficacy and tolerability of entacapone in patients with Parkinson's disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations. A randomized, double-blind, multicentre study. Author(s): Fenelon G, Gimenez-Roldan S, Montastruc JL, Bermejo F, Durif F, Bourdeix I, Pere JJ, Galiano L, Schadrack J. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 March; 110(3): 23951. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658373
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Electrochemical response of dopamine at a penicillamine self-assembled gold electrode. Author(s): Wang Q, Dong D, Li N. Source: Bioelectrochemistry (Amsterdam, Netherlands). 2001 November; 54(2): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11694398
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Endogenous dopamine release after pharmacological challenges in Parkinson's disease. Author(s): Piccini P, Pavese N, Brooks DJ. Source: Annals of Neurology. 2003 May; 53(5): 647-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730999
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Endogenous RGS proteins facilitate dopamine D(2S) receptor coupling to G(alphao) proteins and Ca2+ responses in CHO-K1 cells. Author(s): Boutet-Robinet EA, Finana F, Wurch T, Pauwels PJ, De Vries L. Source: Febs Letters. 2003 January 2; 533(1-3): 67-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505161
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Endogenous risk factors in Parkinson's disease: dopamine and tetrahydroisoquinolines. Author(s): Antkiewicz-Michaluk L. Source: Polish Journal of Pharmacology. 2002 November-December; 54(6): 567-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12866710
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Estimation of the time-course of dopamine D2 receptor occupancy in living human brain from plasma pharmacokinetics of antipsychotics. Author(s): Takano A, Suhara T, Ikoma Y, Yasuno F, Maeda J, Ichimiya T, Sudo Y, Inoue M, Okubo Y. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2004 March; 7(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764214
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Evidence for distinct sodium-, dopamine-, and cocaine-dependent conformational changes in transmembrane segments 7 and 8 of the dopamine transporter. Author(s): Norregaard L, Loland CJ, Gether U. Source: The Journal of Biological Chemistry. 2003 August 15; 278(33): 30587-96. Epub 2003 May 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773538
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Evidence of dopamine D1 receptor mRNA and binding sites in cultured human amniotic epithelial cells. Author(s): Elwan MA, Ishii T, Sakuragawa N. Source: Neuroscience Letters. 2003 July 3; 344(3): 157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812829
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Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. Author(s): Stefanis L, Larsen KE, Rideout HJ, Sulzer D, Greene LA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 December 15; 21(24): 9549-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11739566
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Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Author(s): Xiberas X, Martinot JL, Mallet L, Artiges E, Loc'H C, Maziere B, PaillereMartinot ML. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2001 December; 179: 503-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731352
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Extrastriatal dopamine D 2/3 receptor density and distribution in drug-naive schizophrenic patients. Author(s): Tuppurainen H, Kuikka J, Viinamaki H, Husso-Saastamoinen M, Bergstrom K, Tiihonen J. Source: Molecular Psychiatry. 2003 April; 8(4): 453-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740603
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Extrastriatal dopamine D(2) receptors in Parkinson's disease: a longitudinal study. Author(s): Kaasinen V, Aalto S, NAgren K, Hietala J, Sonninen P, Rinne JO. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 June; 110(6): 591601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768355
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Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study. Author(s): Kotler M, Manor I, Sever Y, Eisenberg J, Cohen H, Ebstein RP, Tyano S. Source: American Journal of Medical Genetics. 2000 June 12; 96(3): 278-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898899
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Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Author(s): Small DM, Jones-Gotman M, Dagher A. Source: Neuroimage. 2003 August; 19(4): 1709-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948725
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Fenoldopam, a dopamine agonist, for hypertensive emergency: a multicenter randomized trial. Fenoldopam Study Group. Author(s): Tumlin JA, Dunbar LM, Oparil S, Buckalew V, Ram CV, Mathur V, Ellis D, McGuire D, Fellmann J, Luther RR. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2000 June; 7(6): 653-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10905644
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Fenoldopam: a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. Author(s): Murphy MB, Murray C, Shorten GD. Source: The New England Journal of Medicine. 2001 November 22; 345(21): 1548-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794223
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Fetal striatal transplants restore electrophysiological sensitivity to dopamine in the lesioned striatum of rats with experimental Huntington's disease. Author(s): Chen GJ, Jeng CH, Lin SZ, Tsai SH, Wang Y, Chiang YH. Source: Journal of Biomedical Science. 2002 July-August; 9(4): 303-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145527
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Fibrosis associated with dopamine agonist therapy in Parkinson's disease. Author(s): Muller T, Fritze J. Source: Clinical Neuropharmacology. 2003 May-June; 26(3): 109-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782910
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Focal dystonia is associated with a polymorphism of the dopamine D5 receptor gene. Author(s): Misbahuddin A, Placzek MR, Warner TT. Source: Adv Neurol. 2004; 94: 143-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509667
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From DOPA to Parkinson's disease: the early history of dopamine research. Author(s): Roe DL. Source: Journal of the History of the Neurosciences. 1997 December; 6(3): 291-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11619865
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From rats to humans and return: testing addiction hypotheses by combined PET imaging and self-reported measures of psychostimulant effects. Commentary on Volkow et al. 'Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies'. Author(s): Di Chiara G. Source: Behavioural Pharmacology. 2002 September; 13(5-6): 371-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394413
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Functional coupling of the human dopamine D2 receptor with G alpha i1, G alpha i2, G alpha i3 and G alpha o G proteins: evidence for agonist regulation of G protein selectivity. Author(s): Gazi L, Nickolls SA, Strange PG. Source: British Journal of Pharmacology. 2003 March; 138(5): 775-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12642378
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Functional imaging of the dopamine system: in vivo evaluation of dopamine deficiency and restoration. Author(s): Sanchez-Pernaute R, Brownell AL, Isacson O. Source: Neurotoxicology. 2002 October; 23(4-5): 469-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428719
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Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease. Author(s): Kaasinen V, Rinne JO. Source: Neuroscience and Biobehavioral Reviews. 2002 November; 26(7): 785-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12470690
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Functional imaging studies on dopamine and motor control. Author(s): Brooks DJ. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2001; 108(11): 1283-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768627
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Further characterization of structural requirements for ligands at the dopamine D(2) and D(3) receptor: exploring the thiophene moiety. Author(s): Dijkstra D, Rodenhuis N, Vermeulen ES, Pugsley TA, Wise LD, Wikstrom HV. Source: Journal of Medicinal Chemistry. 2002 July 4; 45(14): 3022-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12086487
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Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene. Author(s): Roman T, Schmitz M, Polanczyk GV, Eizirik M, Rohde LA, Hutz MH. Source: American Journal of Medical Genetics. 2002 March 8; 114(2): 154-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857576
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Further evidence for the role of the dopamine D4 receptor (DRD4) gene in attachment disorganization: interaction of the exon III 48-bp repeat and the -521 C/T promoter polymorphisms. Author(s): Lakatos K, Nemoda Z, Toth I, Ronai Z, Ney K, Sasvari- Szekely M, Gervai J. Source: Molecular Psychiatry. 2002; 7(1): 27-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11803443
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Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Author(s): Barr CL, Wigg KG, Bloom S, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL. Source: American Journal of Medical Genetics. 2000 June 12; 96(3): 262-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898896
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Further evidence supporting the association between the dopamine receptor D2 Ser/Cys311 variant and disorganized symptomatology of schizophrenia. Author(s): Serretti A, Lilli R, Lorenzi C, Smeraldi E. Source: Schizophrenia Research. 2000 June 16; 43(2-3): 161-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11001590
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Fused azaindole derivatives: molecular design, synthesis and in vitro pharmacology leading to the preferential dopamine D3 receptor agonist FAUC 725. Author(s): Lober S, Hubner H, Gmeiner P. Source: Bioorganic & Medicinal Chemistry Letters. 2002 September 2; 12(17): 2377-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161137
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Galpha12- and Galpha13-protein subunit linkage of D5 dopamine receptors in the nephron. Author(s): Zheng S, Yu P, Zeng C, Wang Z, Yang Z, Andrews PM, Felder RA, Jose PA. Source: Hypertension. 2003 March; 41(3): 604-10. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623966
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Gender-specific molecular heterosis and association studies: dopamine D2 receptor gene and smoking. Author(s): Lee HS. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627467
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Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia. Author(s): Lee HS, Kim SH, Lee HJ, Kim L, Lee SK, Jang DW, Lee MS, Son BG, Suh KY, Kim S. Source: American Journal of Medical Genetics. 2002 August 8; 114(6): 593-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210271
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Gene and protein expression profiles of anti- and pro-apoptotic actions of dopamine, R-apomorphine, green tea polyphenol (-)-epigallocatechine-3-gallate, and melatonin. Author(s): Weinreb O, Mandel S, Youdim MB. Source: Annals of the New York Academy of Sciences. 2003 May; 993: 351-61; Discussion 387-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853328
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Gene therapy for Parkinson's disease: determining the genes necessary for optimal dopamine replacement in rat models. Author(s): Kang UJ, Lee WY, Chang JW. Source: Hum Cell. 2001 March; 14(1): 39-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11436352
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General anesthetic actions on norepinephrine, dopamine, and gamma-aminobutyric acid transporters in stably transfected cells. Author(s): Shahani SK, Lingamaneni R, Hemmings HC Jr. Source: Anesthesia and Analgesia. 2002 October; 95(4): 893-9, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12351264
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Generation of an activating Zn(2+) switch in the dopamine transporter: mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle. Author(s): Loland CJ, Norregaard L, Litman T, Gether U. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 February 5; 99(3): 1683-8. Epub 2002 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11818545
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Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism. Author(s): Costa-Mallen P, Costa LG, Smith-Weller T, Franklin GM, Swanson PD, Checkoway H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 October; 69(4): 535-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10990520
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Genetic polymorphisms of serotonin and dopamine transporters in mental disorders. Author(s): Ueno S. Source: J Med Invest. 2003 February; 50(1-2): 25-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630565
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Genetic polymorphisms of the dopamine D2 and D3 receptor and neuroleptic drug effects in schizophrenic patients. Author(s): Dahmen N, Muller MJ, Germeyer S, Rujescu D, Anghelescu I, Hiemke C, Wetzel H. Source: Schizophrenia Research. 2001 April 15; 49(1-2): 223-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11428346
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Genetic polymorphisms of the promoter region of dopamine D2 receptor and dopamine transporter genes and alcoholism among four aboriginal groups and Han Chinese in Taiwan. Author(s): Chen WJ, Chen CH, Huang J, Hsu YP, Seow SV, Chen CC, Cheng AT. Source: Psychiatric Genetics. 2001 December; 11(4): 187-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807408
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Genetics of childhood disorders: XXII. ADHD, Part 6: The dopamine D4 receptor gene. Author(s): Barr CL. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 January; 40(1): 118-21. Erratum In: J Am Acad Child Adolesc Psychiatry 2001 March; 40(3): 382. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195554
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Genomic organization and promoter characterization of the murine dopamine receptor regulating factor (DRRF) gene. Author(s): Lee SH, Kim YM, Yajima S, Ha JM, Ha BJ, Kim OS, Ohsawa K, Mouradian MM. Source: Gene. 2003 January 30; 304: 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12568728
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Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression. Author(s): Cubells JF, Price LH, Meyers BS, Anderson GM, Zabetian CP, Alexopoulos GS, Nelson JC, Sanacora G, Kirwin P, Carpenter L, Malison RT, Gelernter J. Source: Biological Psychiatry. 2002 March 1; 51(5): 358-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904129
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Genotyping the -521C/T functional polymorphism in the promoter region of dopamine D4 receptor (DRD4) gene. Author(s): Ronai Z, Barta C, Guttman A, Lakatos K, Gervai J, Staub M, Sasvari-Szekely M. Source: Electrophoresis. 2001 April; 22(6): 1102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358133
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Getting formal with dopamine and reward. Author(s): Schultz W. Source: Neuron. 2002 October 10; 36(2): 241-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383780
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Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Author(s): Laruelle M, Kegeles LS, Abi-Dargham A. Source: Annals of the New York Academy of Sciences. 2003 November; 1003: 138-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684442
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Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. Author(s): Gainetdinov RR, Mohn AR, Bohn LM, Caron MG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 September 25; 98(20): 11047-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11572967
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Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis by activating NF-kappa B via Ref-1. Author(s): Daily D, Vlamis-Gardikas A, Offen D, Mittelman L, Melamed E, Holmgren A, Barzilai A. Source: The Journal of Biological Chemistry. 2001 January 12; 276(2): 1335-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035035
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G-protein sensitivity of ligand binding to human dopamine D(2) and D(3) receptors expressed in Escherichia coli: clues for a constrained D(3) receptor structure. Author(s): Vanhauwe JF, Josson K, Luyten WH, Driessen AJ, Leysen JE. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 October; 295(1): 274-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10991990
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Hair loss induced by dopamine agonist: case report and review of the literature. Author(s): Miwa H, Kondo T. Source: Parkinsonism & Related Disorders. 2003 October; 10(1): 51-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499208
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Half a century of antipsychotics and still a central role for dopamine D2 receptors. Author(s): Kapur S, Mamo D. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 October; 27(7): 1081-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642968
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HAND2 synergistically enhances transcription of dopamine-beta-hydroxylase in the presence of Phox2a. Author(s): Xu H, Firulli AB, Zhang X, Howard MJ. Source: Developmental Biology. 2003 October 1; 262(1): 183-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512028
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Harmful drinking in military veterans with post-traumatic stress disorder: association with the D2 dopamine receptor A1 allele. Author(s): Young RM, Lawford BR, Noble EP, Kann B, Wilkie A, Ritchie T, Arnold L, Shadforth S. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2002 September-October; 37(5): 451-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217937
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Heart failure, aging, and renal synthesis of dopamine. Author(s): Ferreira A, Bettencourt P, Pestana M, Correia F, Serrao P, Martins L, Cerqueira-Gomes M, Soares-Da-Silva P. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 September; 38(3): 502-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11532681
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Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation. Author(s): Lundby C, Moller P, Kanstrup IL, Olsen NV. Source: Clinical Science (London, England : 1979). 2001 October; 101(4): 377-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566075
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Hemi-parkinsonism due to a midbrain arteriovenous malformation: dopamine transporter imaging. Author(s): Goldstein S, Friedman JH, Innis R, Seibyl J, Marek K. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2001 March; 16(2): 350-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295793
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Heterologous sensitization of recombinant adenylate cyclases by activation of D(2) dopamine receptors. Author(s): Cumbay MG, Watts VJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 June; 297(3): 1201-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11356947
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High prevalence of rare dopamine receptor D4 alleles in children diagnosed with attention-deficit hyperactivity disorder. Author(s): Grady DL, Chi HC, Ding YC, Smith M, Wang E, Schuck S, Flodman P, Spence MA, Swanson JM, Moyzis RK. Source: Molecular Psychiatry. 2003 May; 8(5): 536-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808433
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Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease. Author(s): Kemppainen N, Laine M, Laakso MP, Kaasinen V, Nagren K, Vahlberg T, Kurki T, Rinne JO. Source: The European Journal of Neuroscience. 2003 July; 18(1): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859348
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Historical development of the dopamine hypothesis of schizophrenia. Author(s): Baumeister AA, Francis JL. Source: Journal of the History of the Neurosciences. 2002 September; 11(3): 265-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481477
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Homologous regulation of the heptahelical D1A receptor responsiveness: specific cytoplasmic tail regions mediate dopamine-induced phosphorylation, desensitization and endocytosis. Author(s): Jackson A, Iwasiow RM, Chaar ZY, Nantel MF, Tiberi M. Source: Journal of Neurochemistry. 2002 August; 82(3): 683-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12153492
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How valid is dopamine transporter imaging as a surrogate marker in research trials in Parkinson's disease? Author(s): Morrish PK. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 October; 18 Suppl 7: S63-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531048
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Human act and AR1 sequences differentially regulate murine and human D1A dopamine receptor promoters. Author(s): Kim OS, Kim HJ, Kwak HJ, Lee JH, Lee YC, Park M, Kim MH, Lee G, Lee SH. Source: Molecules and Cells. 2003 June 30; 15(3): 294-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872983
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Human alpha-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Author(s): Junn E, Mouradian MM. Source: Neuroscience Letters. 2002 March 8; 320(3): 146-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11852183
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Human dopamine transporter gene variation: effects of protein coding variants V55A and V382A on expression and uptake activities. Author(s): Lin Z, Uhl GR. Source: The Pharmacogenomics Journal. 2003; 3(3): 159-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815364
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Human zinc finger protein 161, a novel transcriptional activator of the dopamine transporter. Author(s): Lee KH, Kwak YD, Kim DH, Chang MY, Lee YS, Lee YS. Source: Biochemical and Biophysical Research Communications. 2004 January 23; 313(4): 969-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706637
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Hydrogen peroxide induces loss of dopamine transporter activity: a calciumdependent oxidative mechanism. Author(s): Huang CL, Huang NK, Shyue SK, Chern Y. Source: Journal of Neurochemistry. 2003 September; 86(5): 1247-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911632
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Hypotension in a woman with a metastatic dopamine-secreting carotid body tumor. Author(s): Koch CA, Rodbard JS, Brouwers FM, Eisenhofer G, Pacak K. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2003 July-August; 9(4): 3104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561577
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Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4methylenedioxy-methamphetamine ('ecstasy') use history: correlation with dopamine receptor sensitivity. Author(s): Gerra G, Bassignana S, Zaimovic A, Moi G, Bussandri M, Caccavari R, Brambilla F, Molina E. Source: Psychiatry Research. 2003 September 30; 120(2): 115-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527643
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Identification of intracellular residues in the dopamine transporter critical for regulation of transporter conformation and cocaine binding. Author(s): Loland CJ, Granas C, Javitch JA, Gether U. Source: The Journal of Biological Chemistry. 2004 January 30; 279(5): 3228-38. Epub 2003 November 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597628
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Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. Author(s): Martinez D, Slifstein M, Broft A, Mawlawi O, Hwang DR, Huang Y, Cooper T, Kegeles L, Zarahn E, Abi-Dargham A, Haber SN, Laruelle M. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2003 March; 23(3): 285300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621304
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Imaging the dopamine system to assess disease-modifying drugs: studies comparing dopamine agonists and levodopa. Author(s): Marek K, Jennings D, Seibyl J. Source: Neurology. 2003 September 23; 61(6 Suppl 3): S43-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504379
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Implantation of human amniotic epithelial cells prevents the degeneration of nigral dopamine neurons in rats with 6-hydroxydopamine lesions. Author(s): Kakishita K, Nakao N, Sakuragawa N, Itakura T. Source: Brain Research. 2003 August 1; 980(1): 48-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865158
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Impulsiveness as the intermediate link between the dopamine receptor D2 gene and alcohol dependence. Author(s): Limosin F, Loze JY, Dubertret C, Gouya L, Ades J, Rouillon F, Gorwood P. Source: Psychiatric Genetics. 2003 June; 13(2): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782972
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In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Author(s): Learned-Coughlin SM, Bergstrom M, Savitcheva I, Ascher J, Schmith VD, Langstrom B. Source: Biological Psychiatry. 2003 October 15; 54(8): 800-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550679
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In vivo dopamine pre-synaptic receptors and antioxidant activities in patients with Alzheimer's disease, dementia with Lewy bodies and in controls. A preliminary report. Author(s): Tabet N, Walker Z, Mantle D, Costa D, Orrell M. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(1): 46-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714800
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Increased dopamine and its metabolites in SH-SY5Y neuroblastoma cells that express tyrosinase. Author(s): Hasegawa T, Matsuzaki M, Takeda A, Kikuchi A, Furukawa K, Shibahara S, Itoyama Y. Source: Journal of Neurochemistry. 2003 October; 87(2): 470-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511124
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Increased dopamine turnover after partial loss of dopaminergic neurons: compensation or toxicity? Author(s): Zigmond MJ, Hastings TG, Perez RG. Source: Parkinsonism & Related Disorders. 2002 September; 8(6): 389-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217625
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Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson's disease, and controls. Author(s): Eisensehr I, Linke R, Tatsch K, Kharraz B, Gildehaus JF, Wetter CT, Trenkwalder C, Schwarz J, Noachtar S. Source: Sleep. 2003 August 1; 26(5): 507-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938802
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Increased presynaptic dopamine function in Asperger syndrome. Author(s): Nieminen-von Wendt TS, Metsahonkala L, Kulomaki TA, Aalto S, Autti TH, Vanhala R, Eskola O, Bergman J, Hietala JA, von Wendt LO. Source: Neuroreport. 2004 April 9; 15(5): 757-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15073509
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Inhibition of cocaine binding to the human dopamine transporter by a single chain anti-idiotypic antibody: its cloning, expression, and functional properties. Author(s): Ho M, Segre M. Source: Biochimica Et Biophysica Acta. 2003 July 30; 1638(3): 257-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878327
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Initial human PET imaging studies with the dopamine transporter ligand 18F-FECNT. Author(s): Davis MR, Votaw JR, Bremner JD, Byas-Smith MG, Faber TL, Voll RJ, Hoffman JM, Grafton ST, Kilts CD, Goodman MM. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 June; 44(6): 855-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791810
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Interaction between dopamine and its transporter: role of intracellular sodium ions and membrane potential. Author(s): Chen N, Reith ME. Source: Journal of Neurochemistry. 2004 May; 89(3): 750-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086531
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Interaction between polymorphisms of the dopamine D3 receptor and manganese superoxide dismutase genes in susceptibility to tardive dyskinesia. Author(s): Zhang ZJ, Zhang XB, Hou G, Yao H, Reynolds GP. Source: Psychiatric Genetics. 2003 September; 13(3): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960753
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Interaction of the D2short dopamine receptor with G proteins: analysis of receptor/G protein selectivity. Author(s): Nickolls SA, Strange PG. Source: Biochemical Pharmacology. 2003 April 1; 65(7): 1139-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663049
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Introduction. Dopamine and Parkinson's disease. Author(s): Triarhou LC. Source: Advances in Experimental Medicine and Biology. 2002; 517: 1-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580304
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Inverse relationship between the contents of neuromelanin pigment and the vesicular monoamine transporter-2: human midbrain dopamine neurons. Author(s): Liang CL, Nelson O, Yazdani U, Pasbakhsh P, German DC. Source: The Journal of Comparative Neurology. 2004 May 17; 473(1): 97-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15067721
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Is frequent dosing with ecstasy a risky business for dopamine-containing neurons? Author(s): O'Shea E, Colado MI. Source: Trends in Pharmacological Sciences. 2003 June; 24(6): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823951
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Is there still a place for dopamine in the modern intensive care unit? Author(s): Debaveye YA, Van den Berghe GH. Source: Anesthesia and Analgesia. 2004 February; 98(2): 461-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742388
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Ketamine does not decrease striatal dopamine D2 receptor binding in man. Author(s): Aalto S, Hirvonen J, Kajander J, Scheinin H, Nagren K, Vilkman H, Gustafsson L, Syvalahti E, Hietala J. Source: Psychopharmacology. 2002 December; 164(4): 401-6. Epub 2002 October 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457270
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Ketamine has equal affinity for NMDA receptors and the high-affinity state of the dopamine D2 receptor. Author(s): Kapur S, Seeman P. Source: Biological Psychiatry. 2001 June 1; 49(11): 954-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11398792
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Kinetic interactions of dopamine and dobutamine with human catechol-Omethyltransferase and monoamine oxidase in vitro. Author(s): Yan M, Webster LT Jr, Blumer JL. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 April; 301(1): 315-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907189
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Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alphasynuclein adduct. Author(s): Conway KA, Rochet JC, Bieganski RM, Lansbury PT Jr. Source: Science. 2001 November 9; 294(5545): 1346-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701929
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L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Author(s): Kaiser R, Hofer A, Grapengiesser A, Gasser T, Kupsch A, Roots I, Brockmoller J. Source: Neurology. 2003 June 10; 60(11): 1750-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796525
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Lack of association between a polymorphism in the promoter region of the dopamine D2 receptor and personality traits. Author(s): Katsuragi S, Kiyota A, Tsutsumi T, Isogawa K, Nagayama H, Arinami T, Akiyoshi J. Source: Psychiatry Research. 2001 December 15; 105(1-2): 123-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740982
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Lack of association between polymorphisms of the dopamine D4 receptor gene and personality. Author(s): Strobel A, Spinath FM, Angleitner A, Riemann R, Lesch KP. Source: Neuropsychobiology. 2003; 47(1): 52-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606846
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Lack of association in Japanese patients between neuroleptic malignant syndrome and the TaqI A polymorphism of the dopamine D2 receptor gene. Author(s): Kishida I, Kawanishi C, Furuno T, Matsumura T, Hasegawa H, Sugiyama N, Suzuki K, Yamada Y, Kosaka K. Source: Psychiatric Genetics. 2003 March; 13(1): 55-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605103
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Lack of effect of polymorphisms in dopamine metabolism related genes on imaging of TRODAT-1 in striatum of asymptomatic volunteers and patients with Parkinson's disease. Author(s): Lynch DR, Mozley PD, Sokol S, Maas NM, Balcer LJ, Siderowf AD. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 July; 18(7): 804-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815660
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Lack of sex differences in striatal dopamine D2 receptor binding in drug-naive schizophrenic patients: an IBZM-SPECT study. Author(s): Parellada E, Lomena F, Catafau AM, Bernardo M, Font M, Fernandez-Egea E, Pavia J, Gutierrez F. Source: Psychiatry Research. 2004 January 15; 130(1): 79-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14972370
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Large dopamine-secreting pheochromocytoma: case report. Author(s): Awada SH, Grisham A, Woods SE. Source: Southern Medical Journal. 2003 September; 96(9): 914-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513991
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Link between dopamine D1 and D2 receptors in rat and human striatal tissues. Author(s): Seeman P, Tallerico T. Source: Synapse (New York, N.Y.). 2003 March 15; 47(4): 250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12539197
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Linkage disequilibrium between dopamine D1 receptor gene (DRD1) and bipolar disorder. Author(s): Ni X, Trakalo JM, Mundo E, Macciardi FM, Parikh S, Lee L, Kennedy JL. Source: Biological Psychiatry. 2002 December 15; 52(12): 1144-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488059
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Lisuride, a dopamine D2 receptor agonist, and anticraving drug expectancy as modifiers of relapse in alcohol dependence. Author(s): Schmidt LG, Kuhn S, Smolka M, Schmidt K, Rommelspacher H. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 February; 26(2): 209-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817496
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Localization of peripheral dopamine D1 and D2 receptors in rat and human seminal vesicles. Author(s): Hyun JS, Baig MR, Yang DY, Leungwattanakij S, Kim KD, Abdel-Mageed AB, Bivalacqua TJ, Hellstrom WJ. Source: Journal of Andrology. 2002 January-February; 23(1): 114-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11783439
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Long term tolerability of high dose ergoline derived dopamine agonist therapy for the treatment of Parkinson's disease. Author(s): Navan P, Bain PG. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 November; 73(5): 602-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397168
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Long-term studies of dopamine agonists. Author(s): Hubble JP. Source: Neurology. 2002 February 26; 58(4 Suppl 1): S42-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909984
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Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. Author(s): Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, Gatley SJ, Miller E, Hitzemann R, Ding YS, Logan J. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 December 1; 21(23): 9414-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717374
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Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery. Author(s): Sumeray M, Robertson C, Lapsley M, Bomanji J, Norman AG, Woolfson RG. Source: Journal of Nephrology. 2001 September-October; 14(5): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11730274
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Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Author(s): Volkow ND, Chang L, Wang GJ, Fowler JS, Ding YS, Sedler M, Logan J, Franceschi D, Gatley J, Hitzemann R, Gifford A, Wong C, Pappas N. Source: The American Journal of Psychiatry. 2001 December; 158(12): 2015-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729018
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Low-dose dopamine in the intensive care unit: DNR or DNRx? Author(s): Rudis MI. Source: Critical Care Medicine. 2001 August; 29(8): 1638-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11505148
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Low-dose dopamine: a systematic review. Author(s): Marik PE. Source: Intensive Care Medicine. 2002 July; 28(7): 877-83. Epub 2002 May 31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12122525
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Lower dopamine transporter binding potential in striatum during depression. Author(s): Meyer JH, Kruger S, Wilson AA, Christensen BK, Goulding VS, Schaffer A, Minifie C, Houle S, Hussey D, Kennedy SH. Source: Neuroreport. 2001 December 21; 12(18): 4121-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742250
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Lymphocytes transport serotonin and dopamine: agony or ecstasy? Author(s): Gordon J, Barnes NM. Source: Trends in Immunology. 2003 August; 24(8): 438-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909457
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Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial. Author(s): Carcoana OV, Mathew JP, Davis E, Byrne DW, Hayslett JP, Hines RL, Garwood S. Source: Anesthesia and Analgesia. 2003 November; 97(5): 1222-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570627
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Marked disparity between age-related changes in dopamine and other presynaptic dopaminergic markers in human striatum. Author(s): Haycock JW, Becker L, Ang L, Furukawa Y, Hornykiewicz O, Kish SJ. Source: Journal of Neurochemistry. 2003 November; 87(3): 574-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535941
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Measurement of dopamine D2-like receptors in postmortem CNS and pituitary: differential regional changes in schizophrenia. Author(s): Dean B, Pavey G, Scarr E, Goeringer K, Copolov DL. Source: Life Sciences. 2004 May 7; 74(25): 3115-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081577
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Mechanisms by which dopamine receptors may influence synaptic plasticity. Author(s): Wolf ME, Mangiavacchi S, Sun X. Source: Annals of the New York Academy of Sciences. 2003 November; 1003: 241-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684450
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Menstrual cycle effects on hypothalamic dopamine receptor function in women with a history of puerperal bipolar disorder. Author(s): Wieck A, Davies RA, Hirst AD, Brown N, Papadopoulos A, Marks MN, Checkley SA, Kumar RC, Campbell IC. Source: Journal of Psychopharmacology (Oxford, England). 2003 June; 17(2): 204-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870568
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Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD). Author(s): Vles JS, Feron FJ, Hendriksen JG, Jolles J, van Kroonenburgh MJ, Weber WE. Source: Neuropediatrics. 2003 April; 34(2): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776228
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Mitogen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity. Author(s): Moron JA, Zakharova I, Ferrer JV, Merrill GA, Hope B, Lafer EM, Lin ZC, Wang JB, Javitch JA, Galli A, Shippenberg TS. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 September 17; 23(24): 8480-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679416
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Modulation of D1-like dopamine receptor function by aldehydic products of lipid peroxidation. Author(s): Shin Y, White BH, Uh M, Sidhu A. Source: Brain Research. 2003 April 4; 968(1): 102-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644268
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Modulation of dopamine transporter function by alpha-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. Author(s): Wersinger C, Prou D, Vernier P, Sidhu A. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 November; 17(14): 2151-3. Epub 2003 September 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958153
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Modulation of striatal single units by expected reward: a spiny neuron model displaying dopamine-induced bistability. Author(s): Gruber AJ, Solla SA, Surmeier DJ, Houk JC. Source: Journal of Neurophysiology. 2003 August; 90(2): 1095-114. Epub 2003 March 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649314
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Molecular anatomy of neuronal interactions with special reference to the dopamine control of striatal functions. Author(s): Bloch B. Source: Eur J Histochem. 2002; 46(4): 293-308. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597614
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Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor: discovery of novel and potent D3 ligands through a hybrid pharmacophoreand structure-based database searching approach. Author(s): Varady J, Wu X, Fang X, Min J, Hu Z, Levant B, Wang S. Source: Journal of Medicinal Chemistry. 2003 October 9; 46(21): 4377-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521403
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Molecular profiling of midbrain dopamine regions in cocaine overdose victims. Author(s): Tang WX, Fasulo WH, Mash DC, Hemby SE. Source: Journal of Neurochemistry. 2003 May; 85(4): 911-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716423
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Mutations in the lipid-binding domain of alpha-synuclein confer overlapping, yet distinct, functional properties in the regulation of dopamine transporter activity. Author(s): Wersinger C, Prou D, Vernier P, Niznik HB, Sidhu A. Source: Molecular and Cellular Neurosciences. 2003 September; 24(1): 91-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550771
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Neurology of Tourette's syndrome (TS) TS as a developmental dopamine disorder: a hypothesis. Author(s): Nomura Y, Segawa M. Source: Brain & Development. 2003 December; 25 Suppl 1: S37-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980371
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Neuroprotection and dopamine agonists. Author(s): Pirtosek Z, Flisar D. Source: Advances in Experimental Medicine and Biology. 2004; 541: 55-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977208
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Neuroprotection in PD--a role for dopamine agonists? Author(s): Schapira AH. Source: Neurology. 2003 September 23; 61(6 Suppl 3): S34-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504378
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Neuroscience. Gambling on dopamine. Author(s): Shizgal P, Arvanitogiannis A. Source: Science. 2003 March 21; 299(5614): 1856-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649473
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Neurotransmission of cognition, part 1, Dopamine is a hitchhiker in frontal cortex: norepinephrine transporters regulate dopamine. Author(s): Stahl SM. Source: The Journal of Clinical Psychiatry. 2003 January; 64(1): 4-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590617
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Neurotransmission of cognition, part 2. Selective NRIs are smart drugs: exploiting regionally selective actions on both dopamine and norepinephrine to enhance cognition. Author(s): Stahl SM. Source: The Journal of Clinical Psychiatry. 2003 February; 64(2): 110-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633117
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Nitrotyrosine as a marker for peroxynitrite-induced neurotoxicity: the beginning or the end of the end of dopamine neurons? Author(s): Kuhn DM, Sakowski SA, Sadidi M, Geddes TJ. Source: Journal of Neurochemistry. 2004 May; 89(3): 529-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086510
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No evidence for association and linkage disequilibrium between dyslexia and markers of four dopamine-related genes. Author(s): Marino C, Giorda R, Vanzin L, Molteni M, Lorusso ML, Nobile M, Baschirotto C, Alda M, Battaglia M. Source: European Child & Adolescent Psychiatry. 2003 August; 12(4): 198-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505070
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No evidence of molecular heterosis at the dopamine D2 receptor gene locus for smoking in schizophrenia. Author(s): Tan EC, Chong SA, Teo YY, Mythily S. Source: American Journal of Medical Genetics. 2003 July 1; 120B(1): 40-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815737
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Nucleus accumbens dopamine and the regulation of effort in food-seeking behavior: implications for studies of natural motivation, psychiatry, and drug abuse. Author(s): Salamone JD, Correa M, Mingote S, Weber SM. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 April; 305(1): 1-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649346
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Oligomerization and trafficking of the human dopamine transporter. Mutational analysis identifies critical domains important for the functional expression of the transporter. Author(s): Torres GE, Carneiro A, Seamans K, Fiorentini C, Sweeney A, Yao WD, Caron MG. Source: The Journal of Biological Chemistry. 2003 January 24; 278(4): 2731-9. Epub 2002 November 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429746
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Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Author(s): Kamiya T, Saitoh O, Yoshioka K, Nakata H. Source: Biochemical and Biophysical Research Communications. 2003 June 27; 306(2): 544-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804599
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Oligomerization of dopamine transporters visualized in living cells by fluorescence resonance energy transfer microscopy. Author(s): Sorkina T, Doolen S, Galperin E, Zahniser NR, Sorkin A. Source: The Journal of Biological Chemistry. 2003 July 25; 278(30): 28274-83. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746456
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Opponent interactions between serotonin and dopamine. Author(s): Daw ND, Kakade S, Dayan P. Source: Neural Networks : the Official Journal of the International Neural Network Society. 2002 June-July; 15(4-6): 603-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371515
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Opposite turning behavior in right-handers and non-right-handers suggests a link between handedness and cerebral dopamine asymmetries. Author(s): Mohr C, Landis T, Bracha HS, Brugger P. Source: Behavioral Neuroscience. 2003 December; 117(6): 1448-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674863
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Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease. Author(s): Moore RY. Source: Parkinsonism & Related Disorders. 2003 August; 9 Suppl 2: S65-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915070
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Overexpression of Cu-Zn superoxide dismutase protects neuroblastoma cells against dopamine cytotoxicity accompanied by increase in their glutathione level. Author(s): Haque ME, Asanuma M, Higashi Y, Miyazaki I, Tanaka K, Ogawa N. Source: Neuroscience Research. 2003 September; 47(1): 31-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941444
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Overexpression of human alpha-synuclein causes dopamine neuron death in primary human mesencephalic culture. Author(s): Zhou W, Schaack J, Zawada WM, Freed CR. Source: Brain Research. 2002 February 1; 926(1-2): 42-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814405
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Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3',5'monophosphate-regulated phosphoprotein in common adenocarcinomas. Author(s): Beckler A, Moskaluk CA, Zaika A, Hampton GM, Powell SM, Frierson HF Jr, El-Rifai W. Source: Cancer. 2003 October 1; 98(7): 1547-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508844
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Oxidation of dopamine to aminochrome as a mechanism for neurodegeneration of dopaminergic systems in Parkinson's disease. Possible neuroprotective role of DTdiaphorase. Author(s): Graumann R, Paris I, Martinez-Alvarado P, Rumanque P, Perez-Pastene C, Cardenas SP, Marin P, Diaz-Grez F, Caviedes R, Caviedes P, Segura-Aguilar J. Source: Polish Journal of Pharmacology. 2002 November-December; 54(6): 573-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12866711
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p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Author(s): Joseph B, Wallen-Mackenzie A, Benoit G, Murata T, Joodmardi E, Okret S, Perlmann T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 December 23; 100(26): 15619-24. Epub 2003 Dec 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671317
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Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients. Author(s): Johnston AJ, Steiner LA, O'Connell M, Chatfield DA, Gupta AK, Menon DK. Source: Intensive Care Medicine. 2004 January; 30(1): 45-50. Epub 2003 October 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586494
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Pharmacological analysis of a dopamine D(2Short):G(alphao) fusion protein expressed in Sf9 cells. Author(s): Gazi L, Wurch T, Lopez-Gimenez JF, Pauwels PJ, Strange PG. Source: Febs Letters. 2003 June 19; 545(2-3): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804767
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Polymorphism in the second intron of dopamine receptor D4 gene in humans and apes. Author(s): Shimada MK, Inoue-Murayama M, Ueda Y, Maejima M, Murayama Y, Takenaka O, Hayasaka I, Ito S. Source: Biochemical and Biophysical Research Communications. 2004 April 16; 316(4): 1186-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044110
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Polymorphisms in the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Author(s): Mill J, Fisher N, Curran S, Richards S, Taylor E, Asherson P. Source: Neuroreport. 2003 August 6; 14(11): 1463-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960764
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Polymorphisms of dopamine receptor and transporter genes and hallucinations in Parkinson's disease. Author(s): Wang J, Zhao C, Chen B, Liu ZL. Source: Neuroscience Letters. 2004 January 30; 355(3): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732464
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Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. Author(s): Huang SY, Lin WW, Ko HC, Lee JF, Wang TJ, Chou YH, Yin SJ, Lu RB. Source: Alcoholism, Clinical and Experimental Research. 2004 March; 28(3): 374-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15084894
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Potent activation of dopamine D3/D2 heterodimers by the antiparkinsonian agents, S32504, pramipexole and ropinirole. Author(s): Maggio R, Scarselli M, Novi F, Millan MJ, Corsini GU. Source: Journal of Neurochemistry. 2003 November; 87(3): 631-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535946
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Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) vs newer (nonergot) dopamine agonists. Author(s): Razmy A, Lang AE, Shapiro CM. Source: Archives of Neurology. 2004 January; 61(1): 97-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732626
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Prolactinomas, dopamine agonists and headache: two case reports. Author(s): Levy MJ, Matharu MS, Goadsby PJ. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 March; 10(2): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603293
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Quantification of D2-like dopamine receptors in the human brain with 18Fdesmethoxyfallypride. Author(s): Grunder G, Siessmeier T, Piel M, Vernaleken I, Buchholz HG, Zhou Y, Hiemke C, Wong DF, Rosch F, Bartenstein P. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 January; 44(1): 109-16. Erratum In: J Nucl Med. 2003 February; 44(2): 145. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12515884
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Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease. Author(s): Prunier C, Payoux P, Guilloteau D, Chalon S, Giraudeau B, Majorel C, Tafani M, Bezard E, Esquerre JP, Baulieu JL. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 May; 44(5): 663-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732666
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Quantitative analysis of striatal dopamine D2 receptors with 123 I-iodolisuride SPECT in degenerative extrapyramidal diseases. Author(s): Prunier C, Tranquart F, Cottier JP, Giraudeau B, Chalon S, Guilloteau D, De Toffol B, Chossat F, Autret A, Besnard JC, Baulieu JL. Source: Nuclear Medicine Communications. 2001 November; 22(11): 1207-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11606886
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Quantitative comparison of functional screening by measuring intracellular Ca2+ with radioligand binding at recombinant human dopamine receptors. Author(s): Kassack MU. Source: Aaps Pharmsci [electronic Resource]. 2002; 4(4): E31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646003
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Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade. Author(s): Tauscher-Wisniewski S, Kapur S, Tauscher J, Jones C, Daskalakis ZJ, Papatheodorou G, Epstein I, Christensen BK, Zipursky RB. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 992-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444812
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Rationale for the use of dopamine agonists as neuroprotective agents in Parkinson's disease. Author(s): Schapira AH, Olanow CW. Source: Annals of Neurology. 2003; 53 Suppl 3: S149-57; Discussion S157-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666106
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Reduced dopamine D4 receptor mRNA expression in lymphocytes of long-term abstinent alcohol and heroin addicts. Author(s): Czermak C, Lehofer M, Wagner EM, Prietl B, Lemonis L, Rohrhofer A, Schauenstein K, Liebmann PM. Source: Addiction (Abingdon, England). 2004 February; 99(2): 251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756717
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Regulation of dopamine D1 receptor function by physical interaction with the NMDA receptors. Author(s): Pei L, Lee FJ, Moszczynska A, Vukusic B, Liu F. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2004 February 4; 24(5): 1149-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762133
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Regulation of dopamine D1 receptor trafficking and desensitization by oligomerization with glutamate N-methyl-D-aspartate receptors. Author(s): Fiorentini C, Gardoni F, Spano P, Di Luca M, Missale C. Source: The Journal of Biological Chemistry. 2003 May 30; 278(22): 20196-202. Epub 2003 March 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646556
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Regulation of lung edema clearance by dopamine. Author(s): Adir Y, Sznajder JI. Source: Isr Med Assoc J. 2003 January; 5(1): 47-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592959
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Reproducibility of 99mTc-TRODAT-1 SPECT measurement of dopamine transporters in Parkinson's disease. Author(s): Hwang WJ, Yao WJ, Wey SP, Ting G. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2004 February; 45(2): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960637
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Risperidone-induced obsessive-compulsive symptoms: serotonin-dopamine imbalance? Author(s): Duggal HS. Source: Journal of Clinical Psychopharmacology. 2003 December; 23(6): 681-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624209
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Role of dopamine receptor agonists in the treatment of restless legs syndrome. Author(s): Happe S, Trenkwalder C. Source: Cns Drugs. 2004; 18(1): 27-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14731057
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Role of dopamine transporter imaging in routine clinical practice. Author(s): Marshall V, Grosset D. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 December; 18(12): 1415-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673877
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Roles of dopamine signaling in nicotine addiction. Author(s): Dani JA. Source: Molecular Psychiatry. 2003 March; 8(3): 255-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660795
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Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. Author(s): Bartoszyk GD, Van Amsterdam C, Greiner HE, Rautenberg W, Russ H, Seyfried CA. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2004 February; 111(2): 113-26. Epub 2003 December 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767715
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Sensitization of neuronal A2A adenosine receptors after persistent D2 dopamine receptor activation. Author(s): Vortherms TA, Watts VJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2004 January; 308(1): 221-7. Epub 2003 October 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14566008
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Signalling pathways involved in the short-term potentiation of dopamine release by BDNF. Author(s): Goggi J, Pullar IA, Carney SL, Bradford HF. Source: Brain Research. 2003 April 4; 968(1): 156-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644273
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Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson's disease. Author(s): Paus S, Brecht HM, Koster J, Seeger G, Klockgether T, Wullner U. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 June; 18(6): 659-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784269
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Stimulation of the subthalamic nucleus in Parkinson's disease does not produce striatal dopamine release. Author(s): Abosch A, Kapur S, Lang AE, Hussey D, Sime E, Miyasaki J, Houle S, Lozano AM. Source: Neurosurgery. 2003 November; 53(5): 1095-102; Discussion 1102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580276
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Structure-activity relationships for substrate recognition by the human dopamine transporter. Author(s): Appell M, Berfield JL, Wang LC, Dunn WJ 3rd, Chen N, Reith ME. Source: Biochemical Pharmacology. 2004 January 15; 67(2): 293-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698042
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Studies on the regulatory properties of the pterin cofactor and dopamine bound at the active site of human phenylalanine hydroxylase. Author(s): Solstad T, Stokka AJ, Andersen OA, Flatmark T. Source: European Journal of Biochemistry / Febs. 2003 March; 270(5): 981-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603331
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Subchronic haloperidol downregulates dopamine synthesis capacity in the brain of schizophrenic patients in vivo. Author(s): Grunder G, Vernaleken I, Muller MJ, Davids E, Heydari N, Buchholz HG, Bartenstein P, Munk OL, Stoeter P, Wong DF, Gjedde A, Cumming P. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 April; 28(4): 787-94. Epub 2002 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655326
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Subthalamic deep brain stimulation does not induce striatal dopamine release in Parkinson's disease. Author(s): Strafella AP, Sadikot AF, Dagher A. Source: Neuroreport. 2003 July 1; 14(9): 1287-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824777
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Switching and combining dopamine agonists. Author(s): Reichmann H, Herting B, Miller A, Sommer U. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 December; 110(12): 1393-400. Epub 2003 January 01. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666411
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Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. Author(s): Presgraves SP, Ahmed T, Borwege S, Joyce JN. Source: Neurotox Res. 2004; 5(8): 579-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15111235
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The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells. Author(s): Kudlacek O, Just H, Korkhov VM, Vartian N, Klinger M, Pankevych H, Yang Q, Nanoff C, Freissmuth M, Boehm S. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28(7): 1317-27. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784121
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The International Sepsis Forum's controversies in sepsis: my initial vasopressor agent in septic shock is dopamine rather than norepinephrine. Author(s): Vincent JL, de Backer D; SCCM. International Sepsis Forum. Source: Critical Care (London, England). 2003 February; 7(1): 6-8. Epub 2002 December 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617729
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The International Sepsis Forum's controversies in sepsis: my initial vasopressor agent in septic shock is norepinephrine rather than dopamine. Author(s): Sharma VK, Dellinger RP; SCCM. International Sepsis Forum. Source: Critical Care (London, England). 2003 February; 7(1): 3-5. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617728
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The placebo effect on mood and behavior: possible role of opioid and dopamine modulation of the hypothalamic-pituitary-adrenal system. Author(s): Sher L. Source: Forschende Komplementarmedizin Und Klassische Naturheilkunde = Research in Complementary and Natural Classical Medicine. 2003 April; 10(2): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808364
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The predicted 3D structure of the human D2 dopamine receptor and the binding site and binding affinities for agonists and antagonists. Author(s): Kalani MY, Vaidehi N, Hall SE, Trabanino RJ, Freddolino PL, Kalani MA, Floriano WB, Kam VW, Goddard WA 3rd. Source: Proceedings of the National Academy of Sciences of the United States of America. 2004 March 16; 101(11): 3815-20. Epub 2004 Mar 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999101
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The second extracellular loop of the dopamine D2 receptor lines the binding-site crevice. Author(s): Shi L, Javitch JA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2004 January 13; 101(2): 440-5. Epub 2004 Jan 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14704269
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The variable effects of dopamine among human isolated arteries commonly used for coronary bypass grafts. Author(s): Katai R, Tsuneyoshi I, Hamasaki J, Onomoto M, Suehiro S, Sakata R, Kanmura Y. Source: Anesthesia and Analgesia. 2004 April; 98(4): 915-20, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041572
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Toxicity of a treatment associating dopamine and disulfiram for catecholaminergic neuroblastoma SH-SY5Y cells: relationships with 3,4-dihydroxyphenylacetaldehyde formation. Author(s): Legros H, Dingeval MG, Janin F, Costentin J, Bonnet JJ. Source: Neurotoxicology. 2004 March; 25(3): 365-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019299
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Transcription factors specifying dopamine phenotype are decreased in cocaine users. Author(s): Bannon MJ, Pruetz B, Barfield E, Schmidt CJ. Source: Neuroreport. 2004 March 1; 15(3): 401-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15094491
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Unaltered dopamine transporter availability in adult attention deficit hyperactivity disorder. Author(s): van Dyck CH, Quinlan DM, Cretella LM, Staley JK, Malison RT, Baldwin RM, Seibyl JP, Innis RB. Source: The American Journal of Psychiatry. 2002 February; 159(2): 309-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823278
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Understanding renal dose dopamine. Author(s): Pierce JD, Morris DA, Clancy RL. Source: Journal of Infusion Nursing : the Official Publication of the Infusion Nurses Society. 2002 November-December; 25(6): 365-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12464793
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Unravelling dopamine (and catecholamine) physiopharmacology in lymphocytes: open questions. Author(s): Cosentino M, Marino F, Bombelli R, Ferrari M, Lecchini S, Frigo G. Source: Trends in Immunology. 2003 November; 24(11): 581-2; Author Reply 582-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596880
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Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia. Author(s): Koh PO, Bergson C, Undie AS, Goldman-Rakic PS, Lidow MS. Source: Archives of General Psychiatry. 2003 March; 60(3): 311-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622665
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Uptake of dopamine by cultured monkey amniotic epithelial cells. Author(s): Elwan MA, Sakuragawa N. Source: European Journal of Pharmacology. 2002 January 25; 435(2-3): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821027
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Urinary dopamine and turn bias in traumatized women with and without PTSD symptoms. Author(s): Glover DA, Powers MB, Bergman L, Smits JA, Telch MJ, Stuber M. Source: Behavioural Brain Research. 2003 September 15; 144(1-2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946604
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Use of creatinine clearances to monitor the effect of low-dose dopamine in critically ill surgical patients. Author(s): Eachempati SR, Reed RL 2nd. Source: The Journal of Surgical Research. 2003 June 1; 112(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873432
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Use of dopamine in acute renal failure. Author(s): Maleck WH, Piper SN, Koetter KP. Source: Critical Care Medicine. 2002 August; 30(8): 1934-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12163835
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Use of the dopamine agonist cabergoline in the treatment of movement disorders. Author(s): Marco AD, Appiah-Kubi LS, Chaudhuri KR. Source: Expert Opinion on Pharmacotherapy. 2002 October; 3(10): 1481-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387694
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Using a dopamine type 1A receptor agonist in high-risk patients to ameliorate contrast-associated nephropathy. Author(s): Chamsuddin AA, Kowalik KJ, Bjarnason H, Dietz CA, Rosenberg MS, Gomes MD, McDermott CM, Hunter DW. Source: Ajr. American Journal of Roentgenology. 2002 September; 179(3): 591-6. Erratum In: Ajr Am J Roentgenol 2002 December; 179(6): 1645. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185025
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Variation of the genes encoding the human glutamate EAAT2, serotonin and dopamine transporters and Susceptibility to idiopathic generalized epilepsy. Author(s): Sander T, Berlin W, Ostapowicz A, Samochowiec J, Gscheidel N, Hoehe MR. Source: Epilepsy Research. 2000 August; 41(1): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10924870
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Variation of variable number of tandem repeat sequences in the 3'-untranslated region of primate dopamine transporter genes that affects reporter gene expression. Author(s): Inoue-Murayama M, Adachi S, Mishima N, Mitani H, Takenaka O, Terao K, Hayasaka I, Ito S, Murayama Y. Source: Neuroscience Letters. 2002 December 16; 334(3): 206-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453630
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Variations in the dopamine beta-hydroxylase gene are not associated with the autonomic disorders, pure autonomic failure, or multiple system atrophy. Author(s): Cho S, Kim CH, Cubells JF, Zabetian CP, Hwang DY, Kim JW, Cohen BM, Biaggioni I, Robertson D, Kim KS. Source: American Journal of Medical Genetics. 2003 July 15; 120A(2): 234-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12833405
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Viral restoration of dopamine to the nucleus accumbens is sufficient to induce a locomotor response to amphetamine. Author(s): Heusner CL, Hnasko TS, Szczypka MS, Liu Y, During MJ, Palmiter RD. Source: Brain Research. 2003 August 8; 980(2): 266-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867267
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Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson's disease? Author(s): Freed CR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 February 19; 99(4): 1755-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11854478
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Worsened agitation with aripiprazole: adverse effect of dopamine partial agonism? Author(s): DeQuardo JR. Source: The Journal of Clinical Psychiatry. 2004 January; 65(1): 132-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976671
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ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene. Author(s): Yang Y, Hwang CK, Junn E, Lee G, Mouradian MM. Source: The Journal of Biological Chemistry. 2000 December 8; 275(49): 38863-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984499
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Zn(2+) site engineering at the oligomeric interface of the dopamine transporter. Author(s): Norgaard-Nielsen K, Norregaard L, Hastrup H, Javitch JA, Gether U. Source: Febs Letters. 2002 July 31; 524(1-3): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135746
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CHAPTER 2. NUTRITION AND DOPAMINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and dopamine.
Finding Nutrition Studies on Dopamine The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “dopamine” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on dopamine: •
Should dietary treatment of phenylketonuria be continued after infancy? Source: Nutrition-reviews (USA). (June 1985). volume 43(6) page 176-177.
Additional consumer oriented references include: •
Vitamin A functions in the regulation of the dopaminergic system in the brain and pituitary gland. Author(s): Department of Nutritional Sciences, University of California, Berkeley 947203104, USA. Source: Wolf, G Nutr-Revolume 1998 December; 56(12): 354-5 0029-6643
The following information is typical of that found when using the “Full IBIDS Database” to search for “dopamine” (or a synonym): •
Case-control study of dopamine transporter-1, monoamine oxidase-B, and catechol-Omethyl transferase polymorphisms in Parkinson's disease. Author(s): Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. Source: Goudreau, J L Maraganore, D M Farrer, M J Lesnick, T G Singleton, A B Bower, J H Hardy, J A Rocca, W A Mov-Disord. 2002 November; 17(6): 1305-11 0885-3185
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Combination of two different dopamine agonists in the management of Parkinson's disease. Author(s): Department of Neurosciences, La Sapienza University, Viale dell'Universita 30, I-00185 Rome, Italy. Source: Stocchi, F Berardelli, A Vacca, L Thomas, A De Pandis, M F Modugno, N Valente, M Ruggieri, S Neurol-Sci. 2002 September; 23 Suppl 2: S115-6 1590-1874
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Differential effects of direct and indirect dopamine agonists on prepulse inhibition: a study in D1 and D2 receptor knock-out mice. Author(s): Alcohol and Drug Abuse Research Center, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, USA. Source: Ralph Williams, R J Lehmann Masten, V Otero Corchon, V Low, M J Geyer, M A J-Neurosci. 2002 November 1; 22(21): 9604-11 1529-2401
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Dopamine D2L receptor knockout mice display deficits in positive and negative reinforcing properties of morphine and in avoidance learning. Author(s): Department of Pharmacology, University of Pennsylvania School of Medicine, M102 John Morgan Building, Philadelphia, PA 19014, USA. Source: Smith, J W Fetsko, L A Xu, R Wang, Y Neuroscience. 2002; 113(4): 755-65 03064522
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Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats. Author(s): Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Source: Vorel, S R Ashby, C R Jr Paul, M Liu, X Hayes, R Hagan, J J Middlemiss, D N Stemp, G Gardner, E L J-Neurosci. 2002 November 1; 22(21): 9595-603 1529-2401
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Dopamine enhancement of NMDA currents in dissociated medium-sized striatal neurons: role of D1 receptors and DARPP-32. Author(s): Mental Retardation Research Center, University of California, Geffen School of Medicine, Los Angeles, California 90095, USA. Source: Flores Hernandez, J Cepeda, C Hernandez Echeagaray, E Calvert, C R Jokel, E S Fienberg, A A Greengard, P Levine, M S J-Neurophysiol. 2002 December; 88(6): 3010-20 0022-3077
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Dopamine enhances EPSCs in layer II-III pyramidal neurons in rat prefrontal cortex. Author(s): Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. Source: Gonzalez Islas, C Hablitz, J J J-Neurosci. 2003 February 1; 23(3): 867-75 1529-2401
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Dopamine induces a PI3-kinase-independent activation of Akt in striatal neurons: a new route to cAMP response element-binding protein phosphorylation. Author(s): Laboratoire de Neurobiologie des Processus Adaptatifs, Centre National de la Recherche Scientifique/Universite Pierre et Marie Curie, Unite Mixte de Recherche 7102, 75005 Paris, France. Source: Brami Cherrier, K Valjent, E Garcia, M Pages, C Hipskind, R A Caboche, J JNeurosci. 2002 October 15; 22(20): 8911-21 1529-2401
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Dopamine may preserve the myocardial oxygen balance better than dobutamine when administered with milrinone. Author(s): Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan. Source: Takamatsu, I Karasawa, F Okuda, T Can-J-Anaesth. 2002 November; 49(9): 96872 0832-610X
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Dopamine modulation of perisomatic and peridendritic inhibition in prefrontal cortex. Author(s): Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. Source: Gao, W J Wang, Y Goldman Rakic, P S J-Neurosci. 2003 March 1; 23(5): 1622-30 1529-2401
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Dopaminergic substitution in Parkinson's disease. Author(s): Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany.
[email protected] Source: Muller, T Expert-Opin-Pharmacother. 2002 October; 3(10): 1393-403 1465-6566
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Effect of centrally injected allopregnanolone on sexual receptivity, luteinizing hormone release, hypothalamic dopamine turnover, and release in female rats. Author(s): Instituto de Medicina y Biologia Experimental de Cuyo (IMBECUCONICET), Catedra de Farmacologia, Facultad de Ciencias Medicas, Mendoza, Argentina. Source: Laconi, M R Cabrera, R J Endocrine. 2002 March; 17(2): 77-83 0969-711X
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Effect of daily dosing duration of direct and indirect dopamine receptor agonists: cocaine cross-tolerance following chronic regimens. Author(s): Department of Psychiatry, Box 3870, Duke University Medical Center, Durham, NC 27710, USA.
[email protected] Source: Ellinwood, E H Davidson, C Yu, G Z King, G R Lee, T H EurNeuropsychopharmacol. 2002 October; 12(5): 407-15 0924-977X
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Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion. Author(s): Catedra de Fisiologia, Departamento de Ciencias Biologicas, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina.
[email protected] Source: Costa, Mde L Loria, A Marchetti, M Balaszczuk, A M Arranz, C T Clin-ExpPharmacol-Physiol. 2002 September; 29(9): 772-6 0305-1870
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Electrochemical behavior of dopamine and ascorbic acid at osmium(II) complex cationic monolayer modified gold electrodes. Author(s): Department of Chemistry, Chonbuk National University, Korea. Source: Zhang, J Jeon, I C Anal-Sci. 2002 October; 18(10): 1085-8 0910-6340
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Evidence that acidosis alters the high-affinity dopamine uptake in rat striatal slices and synaptosomes by different mechanisms partially related to oxidative damage. Author(s): Groupe d'Etudes des Mecanismes Cellulaires de l'Ischemie (GEMCI), UPRES EA 1223, Faculte de Medecine et de Pharmacie, 34 Rue du Jardin des Plantes, BP 199, 86005 Poitiers Cedex, France.
[email protected] Source: Barrier, L Barc, S Fauconneau, B Pontcharraud, R Kelani, A Bestel, E Page, G Neurochem-Int. 2003 January; 42(1): 27-34 0197-0186
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Firing modes of midbrain dopamine cells in the freely moving rat. Author(s): Department of Physiology, School of Medical Sciences, University of Otago, P.O. Box 913, Dunedin, New Zealand.
[email protected] Source: Hyland, B I Reynolds, J N Hay, J Perk, C G Miller, R Neuroscience. 2002; 114(2): 475-92 0306-4522
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G protein preferences for dopamine D2 inhibition of prolactin secretion and DNA synthesis in GH4 pituitary cells. Author(s): Ottawa Health Research Institute, Department of Neuroscience, University of Ottawa, Ottawa, Canada K1H-8M5.
[email protected] Source: Albert, P R Mol-Endocrinol. 2002 August; 16(8): 1903-11 0888-8809
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Generation of dopaminergic neurons from embryonic stem cells. Author(s): Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-00047, Japan.
[email protected] Source: Sasai, Y J-Neurol. 2002 September; 249 Suppl 2: II41-4 0340-5354
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High but not low ECS stimulus intensity augments apomorphine-stimulated dopamine postsynaptic receptor functioning in rats. Author(s): Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India.
[email protected] Source: Andrade, C Srinivasamurthy, G M Vishwasenani, A Prakash, G S Srihari, B S Chandra, J S J-ECT. 2002 June; 18(2): 80-3 1095-0680
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Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Author(s): Section for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
[email protected] Source: Lotharius, J Brundin, P Hum-Mol-Genet. 2002 October 1; 11(20): 2395-407 09646906
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In vivo imaging of brain dopaminergic neurotransmission system in small animals with high-resolution single photon emission computed tomography. Author(s): Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
[email protected]
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Source: Saji, H Iida, Y Kawashima, H Ogawa, M Kitamura, Y Mukai, T Shimazu, S Yoneda, F Anal-Sci. 2003 January; 19(1): 67-71 0910-6340 •
Initial therapy for Parkinson's disease: levodopa vs. dopamine receptor agonists. Author(s): Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0035, Japan. Source: Kondo, T J-Neurol. 2002 September; 249 Suppl 2: II25-9 0340-5354
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Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats. Author(s): Institut National de la Sante et de la Recherche Medicale U 289, Hopital de la salpetriere, Paris, France. Source: Muriel, M P Orieux, G Hirsch, E C Mov-Disord. 2002 November; 17(6): 1174-9 0885-3185
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Levodopa is toxic to dopamine neurons in an in vitro but not an in vivo model of oxidative stress. Author(s): Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA. Source: Mytilineou, C Walker, R H JnoBaptiste, R Olanow, C W J-Pharmacol-Exp-Ther. 2003 February; 304(2): 792-800 0022-3565
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Local application of dopamine inhibits pyramidal tract neuron activity in the rodent motor cortex. Author(s): Program in Neuroscience, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. Source: Awenowicz, P W Porter, L L J-Neurophysiol. 2002 December; 88(6): 3439-51 0022-3077
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Low cumulative manganese exposure affects striatal GABA but not dopamine. Author(s): Environmental Toxicology, University of California, Santa Cruz 95064, USA.
[email protected] Source: Gwiazda, R H Lee, D Sheridan, J Smith, D R Neurotoxicology. 2002 May; 23(1): 69-76 0161-813X
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Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson's disease: effects of dopaminergic treatment. Author(s): Max Planck Institute of Psychiatry, Munich, Germany.
[email protected] Source: Brunner, H Wetter, T C Hogl, B Yassouridis, A Trenkwalder, C Friess, E MovDisord. 2002 September; 17(5): 928-33 0885-3185
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Molecular phenotype of rat striatal neurons expressing the dopamine D5 receptor subtype. Author(s): Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Avda Dr Arce 37, 28002 Madrid, Spain. Source: Rivera, A Alberti, I Martin, A B Narvaez, J A de la Calle, A Moratalla, R Eur-JNeurosci. 2002 December; 16(11): 2049-58 0953-816X
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PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], a new MAO-B inhibitor, attenuates MPTP-induced depletion of striatal dopamine levels in C57/BL6 mice. Author(s): Institut de Neurociencia, Department de Bioquimica y Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, Campus Universitari (Bellaterra), 08193 Barcelona, Spain.
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Source: Perez, V Unzeta, M Neurochem-Int. 2003 February; 42(3): 221-9 0197-0186 •
Regulation of medial prefrontal cortex dopamine by alpha-amino-3-hydroxy-5methylisoxazole-4-propionate/kainate receptors. Author(s): Alcohol and Drug Abuse Program, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA. Source: Wu, W R Li, N Sorg, B A Neuroscience. 2002; 114(2): 507-16 0306-4522
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Selective destruction of dopaminergic neurons by low concentrations of 6-OHDA and MPP+: protection by acetylsalicylic acid aspirin. Author(s): Department of Neurology, The Albert Einstein College of Medicine, F-121N, 1300 Morris Park Ave, Bronx, NY 10461, USA. Source: Carrasco, E Werner, P Parkinsonism-Relat-Disord. 2002 September; 8(6): 407-11 1353-8020
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Sigma1 receptor agonist-mediated regulation of N-methyl-D-aspartate-stimulated [3H]dopamine release is dependent upon protein kinase C. Author(s): Department of Pharmacology, The George Washington University Medical Center, Washington, DC 20037, USA. Source: Nuwayhid, S J Werling, L L J-Pharmacol-Exp-Ther. 2003 January; 304(1): 364-9 0022-3565
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Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Author(s): Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Source: Wang, M J Lin, W W Chen, H L Chang, Y H Ou, H C Kuo, J S Hong, J S Jeng, K C Eur-J-Neurosci. 2002 December; 16(11): 2103-12 0953-816X
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Tc and Re chelates of 8alpha-amino-6-methyl-ergoline: synthesis and affinity to the dopamine D2 receptor. Author(s): Forschungszentrum Rossendorf e.V., Institut fur Bioanorganische und Radiopharmazeutische Chemie, D-01314 Dresden, Germany.
[email protected] Source: Spies, H Noll, B Noll, S Findeisen, M Brust, P Syhre, R Berger, R Bioorg-MedChem. 2002 November; 10(11): 3523-8 0968-0896
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The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities. Author(s): Laboratorio de Fisiologia e Farmacologia do SNC, Departamento de Farmacologia, UFPR, Curitiba, PR, Brazil.
[email protected] Source: Da Cunha, C Angelucci, M E Canteras, N S Wonnacott, S Takahashi, R N CellMol-Neurobiol. 2002 June; 22(3): 227-37 0272-4340
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The reinforcing efficacy of the dopamine reuptake inhibitor 2beta-propanoyl-3beta(4-tolyl)-tropane (PTT) as measured by a progressive-ratio schedule and a choice procedure in rhesus monkeys. Author(s): Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. Source: Lile, J A Morgan, D Birmingham, A M Wang, Z Woolverton, W L Davies, H M Nader, M A J-Pharmacol-Exp-Ther. 2002 November; 303(2): 640-8 0022-3565
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The role of astroglia on the survival of dopamine neurons. Author(s): Dpto Neurobiologia-Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain.
[email protected]
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Source: Mena, M A de Bernardo, S Casarejos, M J Canals, S Rodriguez Martin, E MolNeurobiol. 2002 June; 25(3): 245-63 0893-7648 •
Treatment of an acromegalic cat with the dopamine agonist L-deprenyl. Author(s): University of Melbourne Veterinary Clinic and Hospital, Werribee, Victoria. Source: Abraham, L A Helmond, S E Mitten, R W Charles, J A Holloway, S A Aust-Vet-J. 2002 August; 80(8): 479-83 0005-0423
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Ventral striatal anatomy of locomotor activity induced by cocaine, D-amphetamine, dopamine and D1/D2 agonists. Author(s): Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
[email protected] Source: Ikemoto, S Neuroscience. 2002; 113(4): 939-55 0306-4522
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to dopamine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Bromocriptine Alternative names: Parlodel Source: Prima Communications, Inc.www.personalhealthzone.com Chromium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10018,00.html
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Food and Diet Fava Beans Source: Healthnotes, Inc.; www.healthnotes.com Tyramine-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND DOPAMINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to dopamine. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to dopamine and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “dopamine” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to dopamine: •
A herbal medicine used in the treatment of addiction mimics the action of amphetamine on in vitro rat striatal dopamine release. Author(s): Thongsaard W, Marsden CA. Source: Neuroscience Letters. 2002 August 30; 329(2): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165394
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Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson's disease model. Author(s): Park HJ, Lim S, Joo WS, Yin CS, Lee HS, Lee HJ, Seo JC, Leem K, Son YS, Kim YJ, Kim CJ, Kim YS, Chung JH. Source: Experimental Neurology. 2003 March; 180(1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668152
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Acute and chronic actions of a dry methanolic extract of Hypericum perforatum and a hyperforin-rich extract on dopaminergic and serotonergic neurones in rat nucleus
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accumbens. Author(s): Rommelspacher H, Siemanowitz B, Mannel M. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518060 •
Alterations in the function of cerebral dopaminergic and serotonergic systems following electroacupuncture and moxibustion applications: possible correlates with their antistress and psychosomatic actions. Author(s): Yano T, Kato B, Fukuda F, Shinbara H, Yoshimoto K, Ozaki A, Kuriyama K. Source: Neurochemical Research. 2004 January; 29(1): 283-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992288
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Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle. Author(s): Rajakumar N, Leung LS, Ma J, Rajakumar B, Rushlow W. Source: Biological Psychiatry. 2004 April 15; 55(8): 797-803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15050860
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Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NFkappaB) activation and cell death by tea extracts in neuronal cultures. Author(s): Levites Y, Youdim MB, Maor G, Mandel S. Source: Biochemical Pharmacology. 2002 January 1; 63(1): 21-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11754870
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Auditory information processing in rat genotypes with different dopaminergic properties. Author(s): de Bruin NM, van Luijtelaar EL, Cools AR, Ellenbroek BA. Source: Psychopharmacology. 2001 July; 156(2-3): 352-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549235
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Autoradiographic quantification of neurochemical markers of serotonin, dopamine and opioid systems in rat brain mesolimbic regions following chronic St John's wort treatment. Author(s): Chen F, Rezvani AH, Lawrence AJ. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2003 February; 367(2): 12633. Epub 2003 January 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595953
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Bisperoxovanadium complex promotes dopamine exocytosis in PC12 cells. Author(s): Bieger S, Morinville A, Maysinger D.
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Cannabis induced dopamine release: an in-vivo SPECT study. Author(s): Voruganti LN, Slomka P, Zabel P, Mattar A, Awad AG. Source: Psychiatry Research. 2001 October 1; 107(3): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566433
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Chronic repetitive transcranial magnetic stimulation (rTMS) does not affect tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) expression in rats in vivo. Author(s): Hausmann A, Schermer C, Hinterhuber H, Humpel C. Source: Synapse (New York, N.Y.). 2002 October; 46(1): 45-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211098
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Chronic stimulation of D1 dopamine receptors in human SK-N-MC neuroblastoma cells induces nitric-oxide synthase activation and cytotoxicity. Author(s): Chen J, Wersinger C, Sidhu A. Source: The Journal of Biological Chemistry. 2003 July 25; 278(30): 28089-100. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738794
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Comparative study of D2 receptors and dopamine content in striatum before and after electro-acupuncture treatment in rats. Author(s): Lin Y, Lin X. Source: Chinese Medical Journal. 2000 May; 113(5): 408-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776094
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Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Author(s): Bao S, Chan VT, Merzenich MM. Source: Nature. 2001 July 5; 412(6842): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11452310
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Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. Author(s): Gao HM, Liu B, Hong JS. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 July 16; 23(15): 6181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867501
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Danchunhwan water extract prevents apoptotic death by peroxynitrite and nitric oxide in human dopaminergic neuroblastoma SH-SY5Y cells. Author(s): Kim MS, Lee J, So HS, Lee KM, Moon BS, Lee HS, Park R.
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Source: Immunopharmacology and Immunotoxicology. 2001 May; 23(2): 239-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11417851 •
Decreased brain docosahexaenoic acid during development alters dopamine-related behaviors in adult rats that are differentially affected by dietary remediation. Author(s): Levant B, Radel JD, Carlson SE. Source: Behavioural Brain Research. 2004 June 4; 152(1): 49-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15135968
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Destruction of midbrain dopaminergic neurons by using immunotoxin to dopamine transporter. Author(s): Wiley RG, Harrison MB, Levey AI, Lappi DA. Source: Cellular and Molecular Neurobiology. 2003 October; 23(4-5): 839-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514035
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Determination of noradrenaline and dopamine in Chinese herbal extracts from Portulaca oleracea L. by high-performance liquid chromatography. Author(s): Chen J, Shi YP, Liu JY. Source: J Chromatogr A. 2003 June 27; 1003(1-2): 127-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899302
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Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain. Author(s): Innis SM, de La Presa Owens S. Source: The Journal of Nutrition. 2001 January; 131(1): 118-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208947
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Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. Author(s): Duan W, Ladenheim B, Cutler RG, Kruman II, Cadet JL, Mattson MP. Source: Journal of Neurochemistry. 2002 January; 80(1): 101-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796748
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Different effects of five catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells. Author(s): Jin CF, Shen SR Sr, Zhao BL. Source: Journal of Agricultural and Food Chemistry. 2001 December; 49(12): 6033-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743804
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Differential environment alters ontogeny of dopamine innervation of the orbital prefrontal cortex in gerbils. Author(s): Neddens J, Brandenburg K, Teuchert-Noodt G, Dawirs RR.
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Differential up-regulation of striatal dopamine transporter and alpha-synuclein by the pyrethroid insecticide permethrin. Author(s): Gillette JS, Bloomquist JR. Source: Toxicology and Applied Pharmacology. 2003 November 1; 192(3): 287-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575646
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Direct visualization of internalization and intracellular trafficking of dopaminereleasing protein-36aa. Author(s): Smith S, Ramirez VD. Source: Neuroendocrinology. 2002 February; 75(2): 98-112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11867938
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Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. Author(s): Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2000 October 1; 20(19): 7489-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11007908
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Distinct effects of tea catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells. Author(s): Nie G, Jin C, Cao Y, Shen S, Zhao B. Source: Archives of Biochemistry and Biophysics. 2002 January 1; 397(1): 84-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11747313
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Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. Author(s): Gao HM, Hong JS, Zhang W, Liu B. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 February 1; 22(3): 782-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826108
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DL-Tetrahydropalmatine may act through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats. Author(s): Chang CK, Lin MT. Source: Neuroscience Letters. 2001 July 20; 307(3): 163-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11438389
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Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation. Author(s): Saino-Saito S, Berlin R, Baker H. Source: The Journal of Comparative Neurology. 2003 June 16; 461(1): 18-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12722102
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Dopamine and noradrenaline efflux in the rat prefrontal cortex after classical aversive conditioning to an auditory cue. Author(s): Feenstra MG, Vogel M, Botterblom MH, Joosten RN, de Bruin JP. Source: The European Journal of Neuroscience. 2001 March; 13(5): 1051-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11264679
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Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane. Author(s): Dunah AW, Standaert DG. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 August 1; 21(15): 5546-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11466426
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Dopamine denervation of specific striatal subregions differentially affects preparation and execution of a delayed response task in the rat. Author(s): Florio T, Capozzo A, Nisini A, Lupi A, Scarnati E. Source: Behavioural Brain Research. 1999 October; 104(1-2): 51-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11125742
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Dopamine depletion of the nucleus accumbens reverses isolation-induced deficits in prepulse inhibition in rats. Author(s): Powell SB, Geyer MA, Preece MA, Pitcher LK, Reynolds GP, Swerdlow NR. Source: Neuroscience. 2003; 119(1): 233-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763084
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Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea. Author(s): Ruel J, Nouvian R, Gervais d'Aldin C, Pujol R, Eybalin M, Puel JL. Source: The European Journal of Neuroscience. 2001 September; 14(6): 977-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595036
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Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone. Author(s): Sakka N, Sawada H, Izumi Y, Kume T, Katsuki H, Kaneko S, Shimohama S, Akaike A. Source: Neuroreport. 2003 December 19; 14(18): 2425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663204
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Dopamine modulation of activity of cat sensorimotor cortex neurons during conditioned reflexes. Author(s): Storozhuk VM, Khorevin VI, Rozumna NM, Villa AE, Tetko IV. Source: Neuroscience Letters. 2002 September 20; 330(2): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12231439
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Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Author(s): Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R. Source: Nature. 2002 July 4; 418(6893): 50-6. Epub 2002 June 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12077607
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Dopamine operates as a subsecond modulator of food seeking. Author(s): Roitman MF, Stuber GD, Phillips PE, Wightman RM, Carelli RM. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2004 February 11; 24(6): 1265-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960596
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Dopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition. Author(s): Bast T, Pezze MA, Feldon J. Source: Behavioural Pharmacology. 2002 December; 13(8): 669-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12478219
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Dopamine receptor D3 gene and response to lithium prophylaxis in mood disorders. Author(s): Serretti A, Lilli R, Lorenzi C, Franchini L, Smeraldi E. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 1998 December; 1(2): 125-129. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11281956
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Dopamine selectively reduces GABA(B) transmission onto dopaminergic neurones by an unconventional presynaptic action. Author(s): Federici M, Natoli S, Bernardi G, Mercuri NB. Source: The Journal of Physiology. 2002 April 1; 540(Pt 1): 119-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927674
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Dopaminergic modulation of the P50 auditory-evoked potential in a computer model of the CA3 region of the hippocampus: its relationship to sensory gating in schizophrenia. Author(s): Moxon KA, Gerhardt GA, Adler LE.
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Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression. Author(s): Kim JY, Koh HC, Lee JY, Chang MY, Kim YC, Chung HY, Son H, Lee YS, Studer L, McKay R, Lee SH. Source: Journal of Neurochemistry. 2003 June; 85(6): 1443-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787064
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Dynamics of intracellular dopamine contents in the rat brain during the formation of conditioned contextual fear and extinction of an acoustic startle reaction. Author(s): Storozheva ZI, Afanas'ev II, Proshin AT, Kudrin VS. Source: Neuroscience and Behavioral Physiology. 2003 May; 33(4): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774830
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Effect of Bak Foong pills on enhancing dopamine release from the amygdala of female rats. Author(s): Liu B, Dong XL, Xie JX, Gou YL, Rowlands DK, Chan HC. Source: Biological & Pharmaceutical Bulletin. 2003 July; 26(7): 1028-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843633
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Effect of ginseng total saponin on extracellular dopamine release elicited by local infusion of nicotine into the striatum of freely moving rats. Author(s): Shim I, Javaid JI, Kim SE. Source: Planta Medica. 2000 December; 66(8): 705-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11199125
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Effects of acute repetitive transcranial magnetic stimulation on dopamine release in the rat dorsolateral striatum. Author(s): Kanno M, Matsumoto M, Togashi H, Yoshioka M, Mano Y. Source: Journal of the Neurological Sciences. 2004 January 15; 217(1): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675613
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Effects of dopamine antagonists on the timing of two intervals. Author(s): Drew MR, Fairhurst S, Malapani C, Horvitz JC, Balsam PD. Source: Pharmacology, Biochemistry, and Behavior. 2003 April; 75(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759108
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Effects of green tea polyphenols on dopamine uptake and on MPP+ -induced dopamine neuron injury. Author(s): Pan T, Fei J, Zhou X, Jankovic J, Le W.
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Source: Life Sciences. 2003 January 17; 72(9): 1073-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495785 •
Effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells. Author(s): Kim SH, Shin JS, Lee JJ, Yin SY, Kai M, Lee MK. Source: Planta Medica. 2001 October; 67(7): 609-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11582536
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Effects of lifelong dietary exposure to genistein or nonylphenol on amphetaminestimulated striatal dopamine release in male and female rats. Author(s): Ferguson SA, Flynn KM, Delclos KB, Newbold RR, Gough BJ. Source: Neurotoxicology and Teratology. 2002 January-February; 24(1): 37-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836070
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Effects of the dopamine D2 agonist, quinpirole, on time and number processing in rats. Author(s): Santi A, Coppa R, Ross L. Source: Pharmacology, Biochemistry, and Behavior. 2001 January; 68(1): 147-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274719
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Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an [11C]raclopride positron emission tomography study in anesthetized macaque monkeys. Author(s): Ohnishi T, Hayashi T, Okabe S, Nonaka I, Matsuda H, Iida H, Imabayashi E, Watabe H, Miyake Y, Ogawa M, Teramoto N, Ohta Y, Ejima N, Sawada T, Ugawa Y. Source: Biological Psychiatry. 2004 March 1; 55(5): 484-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023576
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Enhancement of the acoustic startle response by dopamine agonists after 6hydroxydopamine lesions of the substantia nigra pars compacta: corresponding changes in c-Fos expression in the caudate-putamen. Author(s): Meloni EG, Davis M. Source: Brain Research. 2000 October 6; 879(1-2): 93-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11011010
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Evidence for the involvement of dopamine in ambulation promoted by menthol in mice. Author(s): Umezu T, Morita M. Source: Journal of Pharmacological Sciences. 2003 February; 91(2): 125-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686756
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Expression of mutant alpha-synucleins enhances dopamine transporter-mediated MPP+ toxicity in vitro. Author(s): Lehmensiek V, Tan EM, Schwarz J, Storch A. Source: Neuroreport. 2002 July 19; 13(10): 1279-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151787
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Fatty acid derivatives of clozapine: prolonged antidopaminergic activity of docosahexaenoylclozapine in the rat. Author(s): Baldessarini RJ, Campbell A, Webb NL, Swindell CS, Flood JG, Shashoua VE, Kula NS, Hemamalini S, Bradley MO. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 January; 24(1): 55-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106876
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Fe(II)-induced DNA damage in alpha-synuclein-transfected human dopaminergic BE(2)-M17 neuroblastoma cells: detection by the Comet assay. Author(s): Martin FL, Williamson SJ, Paleologou KE, Hewitt R, El-Agnaf OM, Allsop D. Source: Journal of Neurochemistry. 2003 November; 87(3): 620-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535945
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GABA in the deep layers of the superior Colliculus/Mesencephalic reticular formation mediates the enhancement of startle by the dopamine D1 receptor agonist SKF 82958 in rats. Author(s): Meloni EG, Davis M. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2000 July 15; 20(14): 5374-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10884322
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Gene and protein expression profiles of anti- and pro-apoptotic actions of dopamine, R-apomorphine, green tea polyphenol (-)-epigallocatechine-3-gallate, and melatonin. Author(s): Weinreb O, Mandel S, Youdim MB. Source: Annals of the New York Academy of Sciences. 2003 May; 993: 351-61; Discussion 387-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853328
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Ginkgo biloba pretreatment partially protects from the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium. Author(s): Rojas P, Rojas-Castaneda J, Vigueras RM, Rojas C. Source: Proc West Pharmacol Soc. 2000; 43: 87-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11056965
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Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress.
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Author(s): Chen XC, Zhu YG, Zhu LA, Huang C, Chen Y, Chen LM, Fang F, Zhou YC, Zhao CH. Source: European Journal of Pharmacology. 2003 July 18; 473(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877931 •
Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected mesencephalic dopaminergic cells. Author(s): Radad K, Gille G, Moldzio R, Saito H, Ishige K, Rausch WD. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2004 January; 111(1): 37-45. Epub 2003 December 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714214
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Glia-conditioned medium induces de novo synthesis of tyrosine hydroxylase and increases dopamine cell survival by differential signaling pathways. Author(s): de Bernardo S, Canals S, Casarejos MJ, Rodriguez-Martin E, Mena MA. Source: Journal of Neuroscience Research. 2003 September 15; 73(6): 818-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949908
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Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. Author(s): Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S. Source: Journal of Neurochemistry. 2001 September; 78(5): 1073-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11553681
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Group I mGluRs coupled to G proteins are regulated by tyrosine kinase in dopamine neurons of the rat midbrain. Author(s): Tozzi A, Guatteo E, Caputi L, Bernardi G, Mercuri NB. Source: Journal of Neurophysiology. 2001 June; 85(6): 2490-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11387395
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Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion. Author(s): Yang ZJ, Camporesi C, Yang X, Wang J, Bosco G, Lok J, Gorji R, Schelper RL, Camporesi EM. Source: European Journal of Applied Physiology. 2002 June; 87(2): 101-7. Epub 2002 April 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12070618
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Hypericum perforatum L (St John's wort) preferentially increases extracellular dopamine levels in the rat prefrontal cortex. Author(s): Yoshitake T, Iizuka R, Yoshitake S, Weikop P, Muller WE, Ogren SO, Kehr J.
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Source: British Journal of Pharmacology. 2004 May 17 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15148244 •
In vitro binding studies with two hypericum perforatum extracts--hyperforin, hypericin and biapigenin--on 5-HT6, 5-HT7, GABA(A)/benzodiazepine, sigma, NPYY1/Y2 receptors and dopamine transporters. Author(s): Gobbi M, Moia M, Pirona L, Morizzoni P, Mennini T. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518075
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Increased dopamine tone during meditation-induced change of consciousness. Author(s): Kjaer TW, Bertelsen C, Piccini P, Brooks D, Alving J, Lou HC. Source: Brain Research. Cognitive Brain Research. 2002 April; 13(2): 255-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11958969
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Increased striatal dopamine turnover following acute administration of rotenone to mice. Author(s): Thiffault C, Langston JW, Di Monte DA. Source: Brain Research. 2000 December 8; 885(2): 283-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102582
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Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins. Author(s): Stull ND, Jung JW, Iacovitti L. Source: Brain Research. Developmental Brain Research. 2001 September 23; 130(1): 91-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557097
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Inhibitory effect of tetrandrine on dopamine biosynthesis and tyrosine hydroxylase in PC12 cells. Author(s): Zhang YH, Fang LH. Source: Planta Medica. 2001 February; 67(1): 77-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11270728
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Long term effects of Toki-shakuyaku-san on brain dopamine and nerve growth factor in olfactory-bulb-lesioned mice. Author(s): Song QH, Toriizuka K, Jin GB, Yabe T, Cyong JC. Source: Japanese Journal of Pharmacology. 2001 June; 86(2): 183-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11459120
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Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery. Author(s): Sumeray M, Robertson C, Lapsley M, Bomanji J, Norman AG, Woolfson RG.
Alternative Medicine 159
Source: Journal of Nephrology. 2001 September-October; 14(5): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11730274 •
Making and repairing the mammalian brain--in vitro production of dopaminergic neurons. Author(s): Perrier AL, Studer L. Source: Seminars in Cell & Developmental Biology. 2003 June; 14(3): 181-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948353
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Mechanism by which brain-derived neurotrophic factor increases dopamine release from the rabbit retina. Author(s): Neal M, Cunningham J, Lever I, Pezet S, Malcangio M. Source: Investigative Ophthalmology & Visual Science. 2003 February; 44(2): 791-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556415
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Mitochondrial complex inhibitors preferentially damage substantia nigra dopamine neurons in rat brain slices. Author(s): Bywood PT, Johnson SM. Source: Experimental Neurology. 2003 January; 179(1): 47-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504867
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Modification of the dopaminergic neurotransmitters in striatum, frontal cortex and hippocampus of rats fed for 21 months with trans isomers of alpha-linolenic acid. Author(s): Acar N, Chardigny JM, Darbois M, Pasquis B, Sebedio JL. Source: Neuroscience Research. 2003 April; 45(4): 375-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657450
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Molecular mechanisms of dopaminergic neurodegeneration: genetic and environmental basis. Author(s): Imam SZ. Source: Annals of the New York Academy of Sciences. 2003 May; 993: 377; Discussion 387-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853331
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Neither the density nor function of striatal dopamine transporters were influenced by chronic n-3 polyunsaturated fatty acid deficiency in rodents. Author(s): Kodas E, Page G, Zimmer L, Vancassel S, Guilloteau D, Durand G, Chalon S. Source: Neuroscience Letters. 2002 March 15; 321(1-2): 95-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11872265
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Neurotrophic and neuroprotective effects of tripchlorolide, an extract of Chinese herb Tripterygium wilfordii Hook F, on dopaminergic neurons. Author(s): Li FQ, Cheng XX, Liang XB, Wang XH, Xue B, He QH, Wang XM, Han JS.
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Source: Experimental Neurology. 2003 January; 179(1): 28-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504865 •
Nicotine and ethanol enhancements of acoustic startle reflex are mediated in part by dopamine in C57BL/6J mice. Author(s): Lewis MC, Gould TJ. Source: Pharmacology, Biochemistry, and Behavior. 2003 August; 76(1): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679231
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Noradrenaline and dopamine efflux in the prefrontal cortex in relation to appetitive classical conditioning. Author(s): Mingote S, de Bruin JP, Feenstra MG. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2004 March 10; 24(10): 2475-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014123
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Optically active N-acetyldopamine dimer of the crude drug “Zentai,” the cast-off shell of the Cicada, Cryptotympana sp. Author(s): Noda N, Kubota S, Miyata Y, Miyahara K. Source: Chemical & Pharmaceutical Bulletin. 2000 November; 48(11): 1749-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11086906
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Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb. Author(s): Baker H, Liu N, Chun HS, Saino S, Berlin R, Volpe B, Son JH. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 November 1; 21(21): 8505-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11606639
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Physiological concentrations of dopamine inhibit the proliferation and cytotoxicity of human CD4+ and CD8+ T cells in vitro: a receptor-mediated mechanism. Author(s): Saha B, Mondal AC, Majumder J, Basu S, Dasgupta PS. Source: Neuroimmunomodulation. 2001; 9(1): 23-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435749
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Postnatal rearing conditions influence ontogeny of adult dopamine transporter (DAT) immunoreactivity of the striatum in gerbils. Author(s): Lehmann K, Teuchert-Noodt G, Dawirs RR. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 September; 109(9): 1129-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12203040
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Postsynaptic dopamine (D(2))-mediated behavioural effects of high acute doses of artemisinin in rodents. Author(s): Amos S, Chindo BA, Abbah J, Vongtau HO, Edmond I, Binda L, Akah PA, Wambebe C, Gamaniel KS. Source: Brain Research Bulletin. 2003 December 30; 62(3): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698358
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Production of dopaminergic neurons for cell therapy in the treatment of Parkinson's disease. Author(s): Peaire AE, Takeshima T, Johnston JM, Isoe K, Nakashima K, Commissiong JW. Source: Journal of Neuroscience Methods. 2003 March 30; 124(1): 61-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648765
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Proteasome mediates dopaminergic neuronal degeneration, and its inhibition causes alpha-synuclein inclusions. Author(s): Sawada H, Kohno R, Kihara T, Izumi Y, Sakka N, Ibi M, Nakanishi M, Nakamizo T, Yamakawa K, Shibasaki H, Yamamoto N, Akaike A, Inden M, Kitamura Y, Taniguchi T, Shimohama S. Source: The Journal of Biological Chemistry. 2004 March 12; 279(11): 10710-9. Epub 2003 December 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672949
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Protective effects of green tea polyphenols and their major component, (-)epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells. Author(s): Nie G, Cao Y, Zhao B. Source: Redox Report : Communications in Free Radical Research. 2002; 7(3): 171-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189048
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Protein tyrosine kinase inhibitors alter human dopamine transporter activity in Xenopus oocytes. Author(s): Doolen S, Zahniser NR. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 March; 296(3): 931-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11181926
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Reaction of oxygen with 6-hydroxydopamine catalyzed by Cu, Fe, Mn, and V complexes: identification of a thermodynamic window for effective metal catalysis. Author(s): Bandy B, Walter PB, Moon J, Davison AJ. Source: Archives of Biochemistry and Biophysics. 2001 May 1; 389(1): 22-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11370668
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Regulation of gonadotropin alpha subunit gene expression by dopamine D(2) receptor agonist in clonal mouse gonadotroph alphaT3-1 cells. Author(s): Kanasaki H, Yonehara T, Yamada Y, Takahashi K, Hata K, Fujiwaki R, Yamamoto H, Takeuchi Y, Fukunaga K, Miyamoto E, Miyazaki K. Source: Biology of Reproduction. 2002 October; 67(4): 1218-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297539
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Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system. Author(s): Keck ME, Welt T, Muller MB, Erhardt A, Ohl F, Toschi N, Holsboer F, Sillaber I. Source: Neuropharmacology. 2002 July; 43(1): 101-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12213264
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Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. Author(s): Strafella AP, Paus T, Barrett J, Dagher A. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 August 1; 21(15): Rc157. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11459878
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Requirement of Gbetagamma and c-Src in D2 dopamine receptor-mediated nuclear factor-kappaB activation. Author(s): Yang M, Zhang H, Voyno-Yasenetskaya T, Ye RD. Source: Molecular Pharmacology. 2003 August; 64(2): 447-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869650
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Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: critical role of developmental stage. Author(s): Kodas E, Vancassel S, Lejeune B, Guilloteau D, Chalon S. Source: Journal of Lipid Research. 2002 August; 43(8): 1209-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12177165
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Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Author(s): Alam M, Schmidt WJ. Source: Behavioural Brain Research. 2002 October 17; 136(1): 317-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385818
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Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum. Author(s): Leng A, Feldon J, Ferger B.
Alternative Medicine 163
Source: Synapse (New York, N.Y.). 2003 December 1; 50(3): 240-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515342 •
Rotenone induces disassembly of the Golgi apparatus in the rat dopaminergic neuroblastoma B65 cell line. Author(s): Diaz-Corrales FJ, Asanuma M, Miyazaki I, Ogawa N. Source: Neuroscience Letters. 2004 January 2; 354(1): 59-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698482
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Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria. Author(s): Kristal BS, Conway AD, Brown AM, Jain JC, Ulluci PA, Li SW, Burke WJ. Source: Free Radical Biology & Medicine. 2001 April 15; 30(8): 924-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295535
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Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways. Author(s): Bloomquist JR, Barlow RL, Gillette JS, Li W, Kirby ML. Source: Neurotoxicology. 2002 October; 23(4-5): 537-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428726
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Selective responding of nucleus accumbens core and shell dopamine to aversively conditioned contextual and discrete stimuli. Author(s): Pezze MA, Heidbreder CA, Feldon J, Murphy CA. Source: Neuroscience. 2001; 108(1): 91-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11738134
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Sensorimotor gating effects produced by repeated dopamine agonists in a paradigm favoring environmental conditioning. Author(s): Feifel D, Priebe K, Johnstone-Miller E, Morgan CJ. Source: Psychopharmacology. 2002 July; 162(2): 138-46. Epub 2002 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12110991
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Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. Author(s): Calapai G, Crupi A, Firenzuoli F, Inferrera G, Squadrito F, Parisi A, De Sarro G, Caputi A. Source: Pharmacopsychiatry. 2001 March; 34(2): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11302563
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Serotonin, serotonin 5-HT(1A) receptors and dopamine in blood peripheral lymphocytes of major depression patients. Author(s): Fajardo O, Galeno J, Urbina M, Carreira I, Lima L.
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Source: International Immunopharmacology. 2003 September; 3(9): 1345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890432 •
Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Author(s): Wang MJ, Lin WW, Chen HL, Chang YH, Ou HC, Kuo JS, Hong JS, Jeng KC. Source: The European Journal of Neuroscience. 2002 December; 16(11): 2103-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12473078
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Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Author(s): Strafella AP, Paus T, Fraraccio M, Dagher A. Source: Brain; a Journal of Neurology. 2003 December; 126(Pt 12): 2609-15. Epub 2003 August 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937078
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Striatal dopaminergic pathways as a target for the insecticides permethrin and chlorpyrifos. Author(s): Karen DJ, Li W, Harp PR, Gillette JS, Bloomquis JR. Source: Neurotoxicology. 2001 December; 22(6): 811-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11829414
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Studies of the biogenic amine transporters. VIII: identification of a novel partial inhibitor of dopamine uptake and dopamine transporter binding. Author(s): Rothman RB, Dersch CM, Carroll FI, Ananthan S. Source: Synapse (New York, N.Y.). 2002 March 15; 43(4): 268-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11835522
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Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Author(s): Sherer TB, Kim JH, Betarbet R, Greenamyre JT. Source: Experimental Neurology. 2003 January; 179(1): 9-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504863
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Suppression of transient 40-Hz auditory response by haloperidol suggests modulation of human selective attention by dopamine D2 receptors. Author(s): Ahveninen J, Kahkonen S, Tiitinen H, Pekkonen E, Huttunen J, Kaakkola S, Ilmoniemi RJ, Jaaskelainen IP. Source: Neuroscience Letters. 2000 September 29; 292(1): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996442
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Sustained extracellular signal-regulated kinase activation by 6-hydroxydopamine: implications for Parkinson's disease. Author(s): Kulich SM, Chu CT. Source: Journal of Neurochemistry. 2001 May; 77(4): 1058-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359871
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Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. Author(s): Gao HM, Hong JS, Zhang W, Liu B. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 February 15; 23(4): 1228-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598611
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The CB1 cannabinoid receptor agonist, HU-210, reduces levodopa-induced rotations in 6-hydroxydopamine-lesioned rats. Author(s): Gilgun-Sherki Y, Melamed E, Mechoulam R, Offen D. Source: Pharmacology & Toxicology. 2003 August; 93(2): 66-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899667
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The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Author(s): Zimmer L, Vancassel S, Cantagrel S, Breton P, Delamanche S, Guilloteau D, Durand G, Chalon S. Source: The American Journal of Clinical Nutrition. 2002 April; 75(4): 662-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916751
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The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism. Author(s): Lannuzel A, Michel PP, Hoglinger GU, Champy P, Jousset A, Medja F, Lombes A, Darios F, Gleye C, Laurens A, Hocquemiller R, Hirsch EC, Ruberg M. Source: Neuroscience. 2003; 121(2): 287-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521988
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The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. A novel mechanism of toxicity. Author(s): Lotharius J, O'Malley KL. Source: The Journal of Biological Chemistry. 2000 December 8; 275(49): 38581-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10969076
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The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesencephalic dopaminergic neurons. Author(s): Ahmadi FA, Linseman DA, Grammatopoulos TN, Jones SM, Bouchard RJ, Freed CR, Heidenreich KA, Zawada WM.
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Source: Journal of Neurochemistry. 2003 November; 87(4): 914-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622122 •
The placebo effect on mood and behavior: possible role of opioid and dopamine modulation of the hypothalamic-pituitary-adrenal system. Author(s): Sher L. Source: Forschende Komplementarmedizin Und Klassische Naturheilkunde = Research in Complementary and Natural Classical Medicine. 2003 April; 10(2): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808364
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The power of cueing to circumvent dopamine deficits: a review of physical therapy treatment of gait disturbances in Parkinson's disease. Author(s): Rubinstein TC, Giladi N, Hausdorff JM. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 November; 17(6): 1148-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12465051
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The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice. Author(s): Barr AM, Lehmann-Masten V, Paulus M, Gainetdinov RR, Caron MG, Geyer MA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 February; 29(2): 221-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603268
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The selective toxicity of 1-methyl-4-phenylpyridinium to dopaminergic neurons: the role of mitochondrial complex I and reactive oxygen species revisited. Author(s): Nakamura K, Bindokas VP, Marks JD, Wright DA, Frim DM, Miller RJ, Kang UJ. Source: Molecular Pharmacology. 2000 August; 58(2): 271-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10908294
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Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving. Author(s): Grimm JW, Lu L, Hayashi T, Hope BT, Su TP, Shaham Y. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 February 1; 23(3): 742-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574402
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Toward full restoration of synaptic and terminal function of the dopaminergic system in Parkinson's disease by stem cells. Author(s): Isacson O, Bjorklund LM, Schumacher JM.
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Source: Annals of Neurology. 2003; 53 Suppl 3: S135-46; Discussion S146-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666105 •
Transcranial magnetic stimulation induces increases in extracellular levels of dopamine and glutamate in the nucleus accumbens. Author(s): Zangen A, Hyodo K. Source: Neuroreport. 2002 December 20; 13(18): 2401-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499837
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Transcriptional regulation of the human PRL-releasing peptide (PrRP) receptor gene by a dopamine 2 Receptor agonist: cloning and characterization of the human PrRP receptor gene and its promoter region. Author(s): Ozawa A, Yamada M, Satoh T, Monden T, Hashimoto K, Kohga H, Hashiba Y, Sasaki T, Mori M. Source: Molecular Endocrinology (Baltimore, Md.). 2002 April; 16(4): 785-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923475
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Triptolide, a Chinese herbal extract, protects dopaminergic neurons from inflammation-mediated damage through inhibition of microglial activation. Author(s): Li FQ, Lu XZ, Liang XB, Zhou HF, Xue B, Liu XY, Niu DB, Han JS, Wang XM. Source: Journal of Neuroimmunology. 2004 March; 148(1-2): 24-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14975583
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Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil and dopamine agonists. Author(s): McCarty MF. Source: Medical Hypotheses. 2001 August; 57(2): 258-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11461185
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Ventral tegmental area dopamine neurons mediate the shock sensitization of acoustic startle: a potential site of action for benzodiazepine anxiolytics. Author(s): Gifkins A, Greba Q, Kokkinidis L. Source: Behavioral Neuroscience. 2002 October; 116(5): 785-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12369800
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to dopamine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Phenylketonuria Source: Healthnotes, Inc.; www.healthnotes.com
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PMS Alternative names: Premenstrual Stress Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Shock Source: Integrative Medicine Communications; www.drkoop.com Tardive Dyskinesia Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Acorus Alternative names: Sweet Flag; Acorus calamus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Ava Source: Integrative Medicine Communications; www.drkoop.com Bovine Colostrum Source: Healthnotes, Inc.; www.healthnotes.com Carbidopa/Levodopa Source: Healthnotes, Inc.; www.healthnotes.com Chasteberry Source: Prima Communications, Inc.www.personalhealthzone.com Chasteberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767,00.html Clozapine Source: Healthnotes, Inc.; www.healthnotes.com Corydalis Alternative names: Corydalis turtschaninovii, Corydalis yanhusuo Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com
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Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Kava Source: Prima Communications, Inc.www.personalhealthzone.com Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Levodopa Source: Healthnotes, Inc.; www.healthnotes.com Levodopa/Carbidopa Alternative names: Sinemet Source: Prima Communications, Inc.www.personalhealthzone.com Lobelia Alternative names: Lobelia inflata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lobelia Alternative names: Lobelia inflata, Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Lobelia Inflata Source: Integrative Medicine Communications; www.drkoop.com L-tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Musa Banana Alternative names: Plantain, Banana; Musa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org NADH Source: Prima Communications, Inc.www.personalhealthzone.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Ginseng Source: Integrative Medicine Communications; www.drkoop.com Phenothiazines Source: Prima Communications, Inc.www.personalhealthzone.com Phosphatidylserine (PS) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html Piper Alternative names: Kava; Piper methysticum Forst.f Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe Source: Healthnotes, Inc.; www.healthnotes.com SAMe Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Tyrosine Source: Integrative Medicine Communications; www.drkoop.com Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Chaste; Vitex agnus-castus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON DOPAMINE Overview In this chapter, we will give you a bibliography on recent dissertations relating to dopamine. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “dopamine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dopamine, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Dopamine ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to dopamine. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A study of the behavioural and neurochemical effects of deuterium substitution in DL-dopa, dopamine and beta-phenylethylhydrazine by Dewar, Karen Margaret; PhD from The University of Saskatchewan (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL33665
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Agonist binding to high-affinity dopamine sites by Tedesco, Joseph L; PhD from University of Toronto (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65311
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An investigation into the role of the neuronal calcium sensor NCS-1 in mediating D2 dopamine receptor signaling by Kabbani, Nadine; PhD from The Pennsylvania State University, 2003, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3106264
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Behavioral functions of dopamine in the anterior cingulate cortex by Dent, Mary F.; PhD from Emory University, 2003, 207 pages http://wwwlib.umi.com/dissertations/fullcit/3080313
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Brain development of receptors for dopamine and noradrenaline relation to hyperactivity of young animals by Hartley-Black, Elizabeth J; PhD from University of Toronto (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK62182
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Characterization and manipulation of prefrontal cortex D2 dopamine receptors in the rat by MacLennan, Alexander John; PhD from The University of British Columbia (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39901
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Characterization of actions of dopamine in the pituitary of the goldfish, Carassius auratus by Omeljaniuk, Robert John; PhD from University of Alberta (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL42856
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Characterization of the interaction of the D#1Bb2#1Bs-dopamine receptor with a guanine nucleotide-binding protein by Wreggett, Keith Allen; PhD from Mcgill University (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL31214
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CHOLINERGIC-DOPAMINERGIC INTERACTIONS IN LEARNING AND MEMORY by MCGURK, SUSAN REGINA, PHD from University of California, Los Angeles, 1989, 155 pages http://wwwlib.umi.com/dissertations/fullcit/9003165
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Comparison of actions and interactions of dopamine-based isoquinolines and their noncyclized progenitors by Marshall, Alice Mary; PhD from The University of Western Ontario (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK46043
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D2 dopamine receptor linked transmembrane signalling modulation by estrogen by Borgundvaag, Bjug; PhD from University of Toronto (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL56883
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Direct labelling of multiple dopamine receptor sites by dopamine agonists and antagonists by List, Stephen Joel; PhD from University of Toronto (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK58263
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Dopamine D#1Bb2#1Bs and D#1Bb1#1Bs receptors biochemical characterization by Niznik, Hyman Bernard; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29355
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Dopamine D1 and D2 receptors in schizophrenia, Alzheimer's, Huntington's, and Parkinson's diseases by Bzowej, Natalie Helen; PhD from University of Toronto (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL56988
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Dopamine D-2 receptor mechanisms in the nucleus accumbens involved in signal transmission from the hippocampus to the mesencephalic locomotor region by Yang, Charles Renkin; PhD from The University of Western Ontario (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL36052
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Dopamine D2 receptors in the nucleus accumbens and inhibition of persistent pain in the formalin test by Joshi, Chetan Arvind; MS from University of Missouri - Kansas City, 2003, 52 pages http://wwwlib.umi.com/dissertations/fullcit/1415292
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Dopamine metabolism in pregnancy impact of amino acid supplementation on regional dopaminergic neurons in dams and fetuses by Craig, Rosemary Eleanor Anne; PhD from University of Toronto (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54690
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Dopamine mimicry of aroused gill reflex behaviors in Aplysia californica by Ruben, Peter; PhD from University of Calgary (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK55404
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Dopaminergic modulation of inhibition in the frog olfactory bulb by Davison, Ian Gordon; PhD from Simon Fraser University (Canada), 2003, 206 pages http://wwwlib.umi.com/dissertations/fullcit/NQ81581
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Effect of dopamine depletion on D(1) receptor binding in rat brain; and metabolism studies of D(1) agonist R-[(11)C]SKF 82957 and phosphodiesterase-4 inhibitor R[(11)C]rolipram by Cheung, Hermia; MSc from University of Toronto (Canada), 2003, 97 pages http://wwwlib.umi.com/dissertations/fullcit/MQ78239
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Effects of chronic amphetamine and chronic restraint stress on cholecystokinin modulation of mesolimbic dopamine-mediated behaviour in the rat by Wunderlich, Glen Robert; PhD from University of Toronto (Canada), 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78453
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Effects of kappa receptor and excitatory amino acid receptor agonists on striatal dopamine release in vitro by Clow, Daniel Winston; PhD from Queen's University at Kingston (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL42307
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Effects of morphine on intracranial self-stimulation the involvement of associative factors and the role of ventral tegmental dopamine neurons by Hand, Timothy Henry; PhD from Mcgill University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL24030
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Effects of opioids on the release of dopamine from brain regions in vitro by Marien, Marc Richard; PhD from Queen's University at Kingston (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65911
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Effects of prenatal haloperidol on brain dopamine development by Plach, Nadia Ramona; PhD from Mcmaster University (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK61198
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Electrophysiological investigation of amygdaloid inputs to the ventral pallidum via the nucleus accumbens and their modulation by dopamine by Yim, Conrad Chi Yiu; PhD from The University of Western Ontario (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK56140
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Functional selectivity of dopamine D(2) receptor agonists: Support for agonistspecific receptor states by Arrington, Elaine Grace; PhD from The University of North Carolina at Chapel Hill, 2003, 96 pages http://wwwlib.umi.com/dissertations/fullcit/3086485
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Genetic differences in brain dopamine receptors and their relationship to dopaminergic behaviour by Helmeste, D; PhD from University of Toronto (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK55749
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In vivo microdialysis to investigate serotonin and dopamine neurotransmission in mouse models of psychiatric and degenerative disease by Mathews, Tiffany Anne; PhD from The Pennsylvania State University, 2003, 245 pages http://wwwlib.umi.com/dissertations/fullcit/3114867
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Influences of dopamine and norepinephrine on gonadotropin release in goldfish, Carassius auratus by Chang, John Philip; PhD from University of Alberta (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NL26788
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Interaction of central neurotransmitters in the regulation of adrenal dopamine betahydroxylase by Lima, Lucimey; PhD from Mcgill University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL24039
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Interactions of D1-dopamine receptors with functionally distinct NMDA receptors in striatum by Chapman, David E.; PhD from The University of Utah, 2003, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3100974
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Involvement of mu-opiate receptors in ethanol-induced accumbal dopamine response by Tang, Man Amanda; PhD from The University of Texas at Austin, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3116452
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Low level lead-induced neurotoxicity: The role of dopaminergic and glutamatergic postsynaptic signal integration in the mesocorticolimbic system by Gedeon, Yokabet; PhD from Texas Southern University, 2003, 88 pages http://wwwlib.umi.com/dissertations/fullcit/3118106
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Mechanisms of environmental chemical-induced apoptosis in dopaminergic cells: Critical roles of protein kinase C-delta and relevance to Parkinson's disease by Kitazawa, Masashi; PhD from Iowa State University, 2003, 341 pages http://wwwlib.umi.com/dissertations/fullcit/3085924
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Mesolimbic contribution to dopamine-dependent circling behavior by Colle, Lois Meryl; PhD from Concordia University (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL56088
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Metabolism of 5-hydroxytryptamine and dopamine in the American cockroach, Periplaneta americana by Sloley, Brian Duff; PhD from University of Waterloo (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL20653
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Metallothionein is implicated in zinc(2+) neuroprotection of cultured rat dopaminergic neurons by Gauthier, Michelle Ann; MSc from Queen's University at Kingston (Canada), 2003, 79 pages http://wwwlib.umi.com/dissertations/fullcit/MQ81068
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Neuroanatomical relationship between hypothalamic dopamine and vasoactive intestinal peptide in the regulation of prolactin: Immunocytochemical and tracttracing studies by Al-Zailaie, Khaled A.; PhD from University of Minnesota, 2003, 221 pages http://wwwlib.umi.com/dissertations/fullcit/3095446
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Neurochemical and behavioural correlates of glutamate and dopamine interaction in the rat nucleus accumbens by Taepavarapruk, Pornnarin; PhD from The University of British Columbia (Canada), 2003, 209 pages http://wwwlib.umi.com/dissertations/fullcit/NQ79264
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Neurochemical mechanisms within the mesolimbic dopamine system of sensitization to the locomotor-stimulating effect of cocaine in rodents by Licata, Stephanie Christine; PhD from Boston University, 2003, 142 pages http://wwwlib.umi.com/dissertations/fullcit/3084841
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Norepinephrine and dopamine release by renal nerves by Morgunov, Nikolas; PhD from University of Toronto (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK50317
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Pharmacological and genetic manipulations reveal the opposing roles of the dopamine D2 receptor and tegmental pedunculopontine nucleus in opiate and ethanol motivation by Dockstader, Colleen Lynn; PhD from University of Toronto (Canada), 2003, 176 pages http://wwwlib.umi.com/dissertations/fullcit/NQ84650
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Photoaffinity labeling of canine striatal dopamine D(2) receptors characterization of a novel photaffinity ligand, [(3)H]azido-N-methylspiperone by Grigoriadis, Dimitri Emil; PhD from University of Toronto (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39755
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Physiological actions of dopamine in an avian basal ganglia nucleus essential for vocal learning by Ding, Long; PhD from University of Pennsylvania, 2003, 145 pages http://wwwlib.umi.com/dissertations/fullcit/3095876
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Radiation effects on dopamine-mediated prepulse inhibition in the C57BL/6 mouse by Zuccarelli Miller, Cara Nicole; PhD from Loma Linda University, 2003, 209 pages http://wwwlib.umi.com/dissertations/fullcit/3102327
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RELATIONSHIPS BETWEEN URINARY CATECHOLAMINES AND MEASURED INTELLIGENCE OF EIGHT-YEAR-OLD CHILDREN (EPINEPHRINE, NOREPINEPHRINE, DOPAMINE) by MCCALLISTER, CORLISS JEAN, PHD from Texas A&m University, 1992, 97 pages http://wwwlib.umi.com/dissertations/fullcit/9300478
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Reversibility of methamphetamine neurotoxicity in the nigrostriatal dopamine system of the vervet monkey by Harvey, Dennis C.; PhD from University of California, Los Angeles, 2003, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3094270
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Solubilization, purification and pharmacological characterization of bovine striatal dopamine D-2 receptor by Ramwani, Jairam J; PhD from Mcmaster University (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL35891
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Structural mechanisms underlying ligand recognition and activation of the D(1)-like dopamine receptors by Jassen, Amy Kathleen; PhD from The University of North Carolina at Chapel Hill, 2003, 160 pages http://wwwlib.umi.com/dissertations/fullcit/3112032
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STUDIES ON THE ROLE OF THE MONOAMINE NEURON SYSTEMS IN MAMMALIAN MEMORY RETRIEVAL (DOPAMINE, SEROTONIN, MOUSE) by JUDGE, MARTIN EDWARD, PHD from New York University, 1985, 154 pages http://wwwlib.umi.com/dissertations/fullcit/8604058
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Substituted 2-amino-tetrahydronaphthalenes as affinity and photoaffinity probes for dopamine receptors by Ross, Gregory Michiel; PhD from Mcmaster University (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL57975
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The effect of a dopamine antagonist and an agonist on rats' perception of reward quantity an examination of the anhedonia hypothesis by Martin-Iverson, Mathew Thomas; PhD from The University of British Columbia (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL24215
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The effect of acute antipsychotic administration on dopamine synthesis in rodents and human subjects using 6-[fluorine-18]-L-m-tyrosine by Mamo, David Charles; MSc from University of Toronto (Canada), 2003, 97 pages http://wwwlib.umi.com/dissertations/fullcit/MQ84436
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The effects of high pressures on inert gases and of anaesthetics on rat striatal dopamine in vitro by Paul, Margaret Lorraine; PhD from The University of Western Ontario (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL49309
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The glycoprotein nature of dopamine D1 and D2 receptors by Jarvie, Keith Roger; PhD from University of Toronto (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL56895
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The involvement of the mesolimbic dopamine system in the sexual behavior of the male rat by Mitchell, John B; PhD from Concordia University (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL41654
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The regulation of globus pallidus gene expression by dopamine and the subthalamic nucleus by Luhrs, Lauren Molholm Billings; PhD from University of California, Irvine, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3090272
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The role of dopamine D1 and D2 receptors in operant and place conditioning in rats by Hoffman, Diane C; PhD from Queen's University at Kingston (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL45226
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The role of dopamine in preparatory and consummatory defensive behaviours by Blackburn, James Robert; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50775
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Uncovering the molecular interplays of dopamine D1-like receptor activation by Tumova, Katerina; MSc from University of Ottawa (Canada), 2003, 159 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76550
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Voltammetry as a tool for monitoring dopamine regulation in the striatum: In vivo and in vitro studies by Khan, Amina Saleem; PhD from University of Pittsburgh, 2003, 93 pages http://wwwlib.umi.com/dissertations/fullcit/3117779
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON DOPAMINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “dopamine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dopamine, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Dopamine By performing a patent search focusing on dopamine, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on dopamine: •
(-)-1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as a dopamine-reuptake Inventor(s): Epstein; Joseph William (Monroe, NY), Lippa; Arnold Stan (Ridgewood, NJ) Assignee(s): Dov Pharmaceuticals Inc. (Hackensack, NJ) Patent Number: 6,569,887 Date filed: August 24, 2001 Excerpt(s): The present invention relates to (-)-1-(3,4-dichlorophenyl)-3azabicyclo[3.1.0]hexane and pharmaceutically acceptable salts thereof, compositions comprising (-)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof and methods for treating or preventing a disorder alleviated by inhibiting dopamine reuptake comprising administering to a patient (-)-1-(3,4dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof. Dopamine is a monoamine neurotransmitter that plays a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of dopamine neurotransmission is through reuptake of released dopamine by Na.sup.+ /Cl.sup.- dependent plasma membrane transporters (Hoffman et al., 1998, Front. Neuroendocrinol. 19(3):187-231). Depending on the surrounding ionic conditions, the dopamine transporter can function as a mediator of both inward directed dopamine transport (i.e., "reuptake") and outward directed dopamine transport (i.e., "release"). The functional significance of the dopamine transporter is its regulation of dopamine neurotransmission by terminating the action of dopamine in a synapse via reuptake (Hitri et al., 1994, Clin. Pharmacol. 17:1-22). Attention deficit disorder is a learning disorder involving developmentally inappropriate inattention with or without hyperactivity. The primary signs of attention deficit disorder are a patient's inattention and impulsivity. Inappropriate inattention causes increased rates of activity or reluctance to participate or respond. A patient suffering from attention deficit disorder exhibits a consistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. (See, e.g., U.S. Pat. No. 6,121,261 to Glatt et al.). Web site: http://www.delphion.com/details?pn=US06569887__
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4,4-Disubstituted piperidines, and methods of use thereof Inventor(s): Hoemann; Michael Z. (Marlborough, MA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 6,656,953 Date filed: December 4, 2001 Abstract: One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to
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addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters. Excerpt(s): Dopamine, norepinephrine and serotonin are mammalian monoamine neurotransmitters that play important roles in a wide variety of physiological processes. Therefore, compounds that selectively modulate the activity of these three neurotransmitters, either individually, in pairs, or as a group, promise to serve as agents effective in the treatment of a wide range of maladies, conditions and diseases that afflict mammals due to atypical activities of these neurotransmitters. For example, depression is believed to result from dysfunction in the noradrenergic or serotonergic systems. Furthermore, the noradrenergic system appears to be associated with increased drive, whereas the serotonergic system relates more to changes in mood. Therefore, it is possible that the different symptoms of depression may benefit from drugs acting mainly on one or the other of these neurotransmitter systems. On the other hand, a single compound that selectively affects both the noradrenergic and serotonergic systems should prove effective in the treatment of depression comprising symptoms related to dysfunction in both systems. Dopamine plays a major role in addiction. Many of the concepts that apply to dopamine apply to other neurotransmitters as well. As a chemical messenger, dopamine is similar to adrenaline. Dopamine affects brain processes that control movement, emotional response, and ability to experience pleasure and pain. Regulation of dopamine plays a crucial role in our mental and physical health. Neurons containing the neurotransmitter dopamine are clustered in the midbrain in an area called the substantia nigra. In Parkinson's disease, the dopamine-transmitting neurons in this area die. As a result, the brains of people with Parkinson's disease contain almost no dopamine. To help relieve their symptoms, these patients are given LDOPA, a drug that can be converted in the brain to dopamine. Web site: http://www.delphion.com/details?pn=US06656953__ •
Cocaine receptor binding ligands Inventor(s): Abraham; Philip (Cary, NC), Boja; John W. (Cuyahega Falls, OH), Carroll; Frank I. (Durham, NC), Kuhar; Michael J. (Atlanta, GA), Lewin; Anita H. (Chapel Hill, NC) Assignee(s): Research Triangle Institute (Research Triangle Park, NC) Patent Number: 6,706,880 Date filed: September 20, 2001 Abstract: The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases or in determining the doses of therapeutic agents that occupy significant numbers of receptors.
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Excerpt(s): This invention is directed to a class of binding ligands for cocaine receptors, neurotransmitter transporters and other receptors, neurotransmitter transporters in the brain. Specifically, a novel family of compounds shows high binding specificity and activity, and, in a radiolabeled form, can be used to bind to these receptors, for biochemical assays and imaging techniques. Such imaging is useful for determining effective doses of new drug candidates in human populations. In addition, the high specificity, slow onset and long duration of the action of these compounds at the receptors makes them particularly well suited for therapeutic uses, for example as substitute medication for psychostimulant abuse. Some of these compounds may be useful in treating Parkinson's Disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorders, obesity, panic attacks and disorders, obsessive-compulsive disorder, cocaine, nicotine and alcohol addiction or depression, by virtue of their inhibitory properties at monoamine transporters. Sites of specific interest included cocaine receptors associated with dopamine (DA) transporter sites. Subsequently, in the U.S. PCT Application from which priority is claimed, and which is incorporated herein by reference, the values for R.sub.1 and R.sub.2 were expanded, such that R.sub.1 may be an alkyl of 1-7 carbon atoms, CH.sub.2 CR.sub.3.dbd.CR.sub.4 R.sub.5 wherein R.sub.3 -R.sub.5 are each, independently C.sub.1-6 alkyl, or phenyl compounds of the formula C.sub.6 H.sub.5 (CH.sub.2).sub.y, wherein y=1-6. R.sub.2 may be any of those list above and also C.sub.6 H.sub.5 (CH.sub.2).sub.z, wherein z=1-6. The PCT filing also reveals the affinity of these compounds for cocaine receptors associated with serotonin (5-hydroxytryptamine, 5-HT) transporters, and confirms, for the first time, that the in vitro binding reported in the earlier-filed application, is confirmed in in vivo testing. Specific disclosure for a variety of applications, including using the compounds in both PET and SPECT scanning, wherein either the iodine substituent, or one of the carbon groups is radioactive (I-123, 125 or 131 and C-11) thus providing methods for scanning for the presence of specific cocaine receptors. Such scanning processes may be used to determine physiological conditions associated with dopamine and serotonin re-uptake inhibitors, which are or lead to behavioral and neurodegenerative disorders/diseases. Such disorders include depression, bipolar disorder, eating disorders, obesity, attention deficit disorder, panic attacks and disorders, obsessive-compulsive disorder, Parkinson's Disease, and cocaine, nicotine and alcohol addiction. These compounds, in addition to being used in treatment of these disorders, may be used to examine in general the density and distribution of specific cocaine receptors in various parts of the brain and/or body, to determine the efficacy of neurological treatments aimed at halting or reversing the degeneration of specific nerves in the brain, and for screening drugs, such as antidepressant drugs. The imaging techniques may also be used to determine the doses of novel or potential therapeutic agents that occupy significant quantities of receptors by in vivo competition technique. Web site: http://www.delphion.com/details?pn=US06706880__ •
Dopa and dopamine modification of metal oxide semiconductors, method for attaching biological molecules to semiconductors Inventor(s): Paunesku; Tatjana (Woodridge, IL), Rajh; Tijana (Naperville, IL), Thurnauer; Marion C. (Downers Grove, IL), Woloschak; Gayle E. (Chicago, IL) Assignee(s): University of Chicago (Chicago, IL) Patent Number: 6,677,606 Date filed: June 28, 2000
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Abstract: A method is provided for selective binding and detecting target molecules, and a method for detecting biological molecules, the method comprising supplying a semi-conductor capable of charge pair separation, and juxtaposing affinity moieties to the semi-conductor so as to effect changes in the charge pair separation characteristics when the affinity molecules are bound to the target molecules. Excerpt(s): This invention relates to a method for attaching and detecting the attachment of biological molecules to semiconductors, and more particularly, the invention relates to a method for attaching biologically active molecules to nanoparticle-size metal oxide semi-conductors. Detection of target molecules in an unknown mixture finds a variety of applications. A few of these applications include genome sequencing, forensics, assays, and drug affinity studies. Typical detection techniques involve the use of fluorescence tags. Such tags are first attached to moieties (having known affinities to target molecules), to create a construct. The construct is then combined with materials in a search for the target molecules suspected of residing in those materials. Web site: http://www.delphion.com/details?pn=US06677606__ •
Dopamine D4 ligands for the treatment of novelty-seeking disorders Inventor(s): Fliri; Antor F. (Stonington, CT), Sanner; Mark A. (Old Saybrook, CT), Seymour; Patricia A. (Westerly, RI), Zorn; Stevin H. (No. Stonington, CT) Assignee(s): Pfizer Inc (New York, NY) Patent Number: 6,548,502 Date filed: July 26, 2001 Abstract: The present invention provides a method of treating or preventing a noveltyseeking disorder, such as pathological gambling, attention deficit disorder with hyperactivity disorder and sex addiction, comprising administering a compound which is a dopamine D4 receptor ligand, or a pharmaceutically acceptable salt thereof. Excerpt(s): The present invention relates to a method of treating or preventing a noveltyseeking disorder selected from pathological gambling, attention deficit disorder with hyperactivity disorder, substance addiction, such as drug addiction and alcohol addiction, and sex addiction, using a dopamine D4 ligand. It also relates to a method of treating or preventing such disorders in mammals by administering a pyrido[1,2a]pyrazine derivative, benzimidazole derivative, bicyclic compound, spirocyclic benzo furan derivative, indole derivative or a related compound that is a dopamine D4 receptor ligand. It has been determined that dopamine D4 receptors are related to various behavioral and personality disorders including novelty seeking disorders (See, e.g., Tarazi et al., Mol. Psychiatry, 4, 529-538(1999). The trait of novelty seeking was found to be related to dopaminergic activity in alcoholic men (Wiesbeck et al., Psychoneuroendocrinology, 20, 7(1999)). A large Finnish study provides support for an association between the D4 receptor gene (DRD4) and the behavioral trait of novelty seeking (Ekelund et al., Am. J. Psychiatry, 156, 1453-5 (1999)). Recent evidence has accumulated which supports a clinical linkage between attention deficit disorder with hyperactivity disorder, which has been associated with the novelty seeking trait, and dopamine receptor expression (see, e.g., Tarazi et al., supra; Anderson et al., Neuroscience & Biobehavioral Rev., 24, 137-41 (2000)) and dopamine transporter gene expression (see, e.g., Dougherty et al., The Lancet, 354, 2132-2133 (1999)). Further evidence has been found for an association between the D4 gene and a susceptibility to pathological gambling (Comings, CNS Spectr., 3, 20-37 (1998)) and a susceptibility to
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opioid addiction and substance abuse (Kotler et al., Mol. Psychiatry, 2, 251-254 (1997)). The following references refer, collectively, to pyrido[1,2a]pyrazine derivatives, benzimidazole derivatives, bicyclic compounds, spirocyclic benzofuran derivatives, indole derivatives or related compounds that exhibit activity as dopamine D4 receptor ligands: U.S. Pat. No. 5,852,031, issued on Dec. 22, 1998; U.S. Pat. No. 5,883,094, issued on Mar. 16, 1999; U.S. Pat. No. 5,889,010, issued on Mar. 30, 1999; PCT International Application PCT/IB97/00978, published as WO98/08835 on Mar. 5, 1998; U.S. patent application Ser. No. 5,877,317 issued on Mar. 2, 1999; U.S. patent application Ser. No. 5,021,420, issued on Jun. 4, 1991; U.S. patent application Ser. No. 5,633,376, issued on May 27, 1997; U.S. patent application, Ser. No. 5,432,177, issued on Nov. 9, 1994; U.S. patent application Ser. No. 5,622,950, issued on Apr. 22, 1997, PCT International Application No. PCT/EP93/01438, published as WO94/00458 on Jan. 6, 1994; PCT International Application No. PCT/IB98/01198, published as WO99/09025 on Feb. 25, 1999; U.S. patent application Ser. No. 5,998,414, issued on Dec. 7, 1999; U.S. patent application Ser. No. 5,968,478, issued on Oct. 19, 1999; U.s. patent application Ser. No. 6,040,448, issued on Mar. 21, 2000; U.S. patent application Ser. No. 6,051,605, issued on Apr. 18, 2000; U.S. patent application Ser. No. 5,945,421, issued on Aug. 31, 1999; and U.S. patent application Ser. No. 5,798,350, issued on Aug. 25, 1998. All of the foregoing PCT International Applications designate the United States. The foregoing patents and patent applications are incorporated by reference in their entirety. Web site: http://www.delphion.com/details?pn=US06548502__ •
Dopamine transporter imaging agents Inventor(s): Blundell; Paul (Somerville, MA), Fischman; Alan J. (Boston, MA), Jones; Alun G. (Newton Centre, MA), Madras; Bertha K. (Newton, MA), Mahmood; Ashfaq (Brookline, MA), Meltzer; Peter C. (Lexington, MA) Assignee(s): Organix, Inc. (Woburn, MA), President and Fellow of Harvard College (Cambridge, MA), The General Hospital Corporation (Boston, MA) Patent Number: 6,548,041 Date filed: May 10, 2000 Abstract: Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter over the serotonin transporter with a ratio of 10 or more. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds. Excerpt(s): The present invention relates to coordination complexes comprising a radiolabeled ligand with high binding affinity and good selectivity for the dopamine transporter (DAT). Such agents can be useful for the early diagnosis and treatment of neurodegenerative disorders. The dopamine transporter (DAT) plays a critical role in physiological, pharmacological and pathological processes in brain. The transport system is a primary mechanism for terminating the effects of synaptic dopamine, thereby contributing to the maintenance of homeostasis in dopamine systems. It also appears to be a principal target of cocaine in the brain. (Kennedy and Hanbauer, J. Neurochem. 1983, 41, 172-178; Shoemaker et al., Naunyn-Schmeideberg's Arch. Pharmacol. 1985, 329, 227-235; Reith et al., Biochem Pharmacol. 1986, 35, 1123-15 1129; Ritz et al., Science 1987, 237, 1219-1223; Madras et al., J. Pharmacol. Exp. Ther. 1989a,
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251, 131-141; Bergman et al., J. Pharmacol. Exp. Ther. 1989, 251, 150-155; Madras and Kaufman, Synapse 1994, 18, 261-275). Furthermore, the dopamine transporter may be a conduit for entry of neurotoxins into dopamine containing cells. The striatum has the highest levels of dopamine terminals in the brain. A high density of DAT is localized on dopamine neurons in the striatum and appears to be a marker for a number of physiological and pathological states. For example, in Parkinson's disease, dopamine is severely reduced and the depletion of DAT in the striatum has been an indicator for Parkinson's disease (Schoemaker et al., Naunyn-Schmeideberg's Arch. Pharmacol. 1985, 329, 227-235; Kaufman and Madras, Synapse 1991, 9, 43-49). Consequently, early or presymptomatic diagnosis of Parkinson's disease can be achieved by the quantitative measurement of DAT depletion in the striatum. (Kaufman and Madras, Synapse 1991, 9, 43-49). Simple and noninvasive methods of monitoring the DAT are quite important. Depletion could be measured by a noninvasive means such as brain imaging using a scintillation camera system and a suitable imaging agent (Frost et al., Ann. Neurology 1993, 34, 423-431; Hantraye et al., Neuroreport 1992, 3, 265-268). Imaging of the dopamine transporter also would enable the monitoring of progression of the disease and of reversal of the disease such as with therapies consisting of implants of dopamine neurons or drugs that retard progression of the disease. Web site: http://www.delphion.com/details?pn=US06548041__ •
Method of controlling body temperature while inhibiting thermoregulatory responses Inventor(s): Dae; Michael W. (Belmont, CA), Keller; Wade A. (San Jose, CA), Machold; Timothy R. (Moss Beach, CA) Assignee(s): Radiant Medical, Inc. (Redwood City, CA) Patent Number: 6,572,638 Date filed: April 27, 2001 Abstract: A method and apparatus for controlling the body temperature of a patient while reducing shivering by using a heat exchange device in combination with an antithermoregulatory response mechanism that temporarily reduces shivering. The devices disclosed include a catheter having a heat exchange balloon thereon with heat exchange fluid circulating through the interior of the balloon. The heat exchange balloon is placed in the vasculature of a patient, and heat exchange fluid at a temperature other than the temperature of the blood in the vasculature is circulated through the interior of the balloon to add or remove heat from the blood of the patient. Various antithermoregulatory response agents are disclosed including dopamine receptor blockers, dopamine receptor agonists,.kappa. opioid receptor agonists,.mu. opioid receptor agonists opioid agonist-antagonist analgesics, serotonin 5 HT1a agonists,.alpha.2adrenorceptor agonists, non-opiod analgesic monoamine uptake inhibitors and neuropeptides. Specific examples of each are give. A control system for the control of the patient's temperature is disclosed for controlling the patient's temperature in conjunction with administering the anti-thermoregulatory response mechanism. Excerpt(s): This invention relates to a method, apparatus and composition for selectively controlling the temperature of all or a portion of a patient's body by lowering, maintaining or raising the temperature of a body fluid or tissue to affect the temperature of all or part of the patient's body, while reducing shivering that typically accompanies such temperature control. More particularly, the invention relates to the application of a method, apparatus and composition of a heat exchange device in combination with an
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anti-thermoregulatory response mechanism to control the temperature of all of a portion of a patient's body while reducing shivering, inhibiting vasoconstriction and/or increasing thermal comfort during various therapeutic uses of patient temperature control. The invention also relates to novel compositions that are useful for reducing shivering or inhibiting vasoconstriction. The "set point temperature" is the temperature that the body attempts to maintain through the thermoregulatory responses. Under ordinary circumstances, thermoregulatory responses within the human body which include sweating and vasodilation to enhance heat loss, arterio venous ("AV") shunting and vasoconstriction to enhance retaining heat, and shivering to enhance increased generation of body heat, serve to maintain the body at a near constant set point temperature of about 37.degree. C. (98.6.degree. F.), often referred to as "normothermic". However, sometimes the body sets a different set point temperature, for example a patient with a fever has an elevated set point temperature, and these mechanisms can serve to maintain an elevated temperature. In the case of a fever, the set point temperature can be higher than normothermic. There is a temperature slightly below the set point temperature where the body senses that the body temperature is too low and begins to shiver. This temperature is sometimes referred to as the shivering threshold. As with the set point temperature, the shivering threshold is not an absolute temperature but varies between individuals and within the same individual depending on his or her condition. Web site: http://www.delphion.com/details?pn=US06572638__ •
Method of inducing opioid analgesia and anesthesia without respiratory suppression Inventor(s): Lalley; Peter M. (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 6,706,704 Date filed: November 9, 2001 Abstract: The invention is directed to a pharmaceutical composition and a corresponding method for inhibiting respiratory depression in a mammalian subject during treatment with opiates. The composition contains in combination, an opiate or opioid analgesic or anesthetic and a D.sub.1 -dopamine receptor agonist in an amount sufficient to inhibit respiratory depression caused by the opiate or opioid. Excerpt(s): The invention is directed to method of inducing opioid analgesia and anesthesia in mammals, including humans, without suppressing respiration. Opiates have long been known to disrupt respiratory rhythm and to depress breathing and respiratory sensitivity to CO.sub.2 (Jaffe and Martin, 1990). The pons and medulla are known to be the primary sites where opiate drugs produce these respiratory effects (Id.). Endogenous opioids as well as.mu.- and.delta.-subtypes of opioid receptors are present in essentially all respiratory regions of the pons and medulla (Yeadon and Kitchen, 1989). In vivo and in vitro investigations have shown that exogenous opioids depress inspiratory and expiratory neuronal activity postsynaptically (Denavit-Saubie', Champagnat and Zieglgansberger, 1978), as well as presynaptically (Johnson, Smith and Feldman, 1996). The underlying cellular mechanisms responsible for the opiate effects on respiration have not, however, been elucidated. Opiates are widely used medicinal agents. However, because they depress breathing, their use is contraindicated in many instances, especially in patients with compromised cardiovasculare and pulmonary function. Thus, there has been a long-felt need to harness the analgesic power of the opiates, without depressing the respiratory function of the patient.
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Web site: http://www.delphion.com/details?pn=US06706704__ •
Method of treating parkinson's disease Inventor(s): Svensson; Kjell A. (Portage, MI) Assignee(s): Pharmacia & Upjohn Company (Kalamazoo, MI) Patent Number: 6,653,325 Date filed: October 12, 2001 Abstract: A method of preventing the development of dyskinesias in patients being treated for Parkinson's Disease comprising the administrating a pharmacologically effective amount of a substituted phenylazacycloalkane and a dopamine agonist to the patient. Excerpt(s): The present invention is directed to methods for preventing the development of and treating dyskinesias in patients being treated for Parkinson's disease utilizing substituted phenylazacycloalkanes and dopamine agonists. Parkinson's disease is pathologically associated with a degeneration within the nuclear masses of the extrapyramidal system and the characteristic loss of melanin-containing cells from the substantia nigra and a corresponding reduction in dopamine levels in the corpus striatum. A conventional method of treating Parkinson's disease involves the administration of a dopamine agonist to a patient suffering from this disorder to restore the nigro-neostriatal hypofunction by increasing the post synaptic dopamine receptor stimulation. However, when a dopamine agonist such as L-DOPA is used to treat Parkinson's disease, typically, dyskinesias occur in the patient as a side effect. These dyskinesias usually occur at the peak dosage and may assume one or more of several possible forms such as choreic, dystonic, athetotic or myoponic with varying intensities and sometimes occurs to such an extent that it is worse than the underlying Parkinsonism. It is believed that the development of L-DOPA induced dyskinesias result from severe nigrostriatal denervation in combination with chronic L-DOPA treatment for a period of time of months to years. Once the dyskinesias manifest themselves, the therapeutic options that can be offered to the patient are reduced. U.S. Pat. No. 5,462,947 to Svensson et al discloses substituted phenylazacycloalkanes which possess selective dopamine receptor pharmacological properties and are useful in treating central nervous system disorders such as depression symptoms, geriatric disorders, schizophrenia, narcolepsy, MBD, obesity, disturbances of sexual functions, and rehabilitation of drug abusers. Web site: http://www.delphion.com/details?pn=US06653325__
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Methods of treating or preventing neuropathic pain using sibutramine metabolites Inventor(s): Fang; Qun Kevin (Wellesley, MA), Han; Zhengxu (Shrewsbury, MA), Krishnamurthy; Dhileepkumar (Westboro, MA), Senanayake; Chrisantha Hugh (Shrewsbury, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,710,087 Date filed: June 4, 2002
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Abstract: Methods of making and using racemic and optically pure metabolites of sibutramine, and pharmaceutically acceptable salts, solvates, and clathrates thereof, are disclosed. Pharmaceutical compositions and dosage forms are also disclosed which comprise a dopamine reuptake inhibitor, such as a racemic or optically pure sibutramine metabolite, and optionally an additional pharmacologically active compound. Excerpt(s): The invention relates to compositions comprising dopamine reuptake inhibitors, including racemic and optically pure metabolites of sibutramine, and to methods of making and using the same. Sibutramine, chemically named [N-1-[1-(4chlorophenyl)cyclobutyl]-3-methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al, Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Racemic sibutramine is sold as a hydrochloride monohydrate under the tradename MERIDIA.RTM., and is indicated for the treatment of obesity. Physician's Desk Reference.RTM. 1494-1498 (53.sup.rd ed., 1999). The treatment of obesity using racemic sibutramine is disclosed, for example, in U.S. Pat. No. 5,436,272. Web site: http://www.delphion.com/details?pn=US06710087__ •
Monoclonal antibody antagonists for treating medical problems associated with damphetamine-like drugs Inventor(s): Abraham; Philip (Cary, NC), Carroll; Frank Ivy (Durham, NC), Owens; Samuel M. (Little Rock, AR) Assignee(s): The Board of Trustees of the University of Arkansas (Little Rock, AR) Patent Number: 6,669,937 Date filed: April 20, 2001 Abstract: The invention includes synthetic immunochemical haptens for the generation of antibodies, the antibodies, and the medical treatment applications for using the antibodies. The antibodies are designed to recognize the common molecular features of d-methamphetamine-like abused stimulants, and will have insignificant cross-reactivity with endogenous substrates (e.g. dopamine) or over-the-counter medications (e.g. 1methamphetamine, pseudoephedrine, phenylpropanolamine and ephedrine). These monoclonal antibodies and their antigen binding fragments are useful in treatment plans for recovering addicts, in emergency room settings for rapidly reversing a drug overdose, in protection of fetuses or fetus from drug-abusing pregnant mothers or in a psychiatric setting to reduce the exacerbation of psychotic disorders caused by stimulant drugs. Excerpt(s): The present invention relates generally to the field of drug abuse and addiction therapy. More specifically, the present invent ion relates to the generation and use of high affinity monoclonal antibodies (MAb) and their derivatives as long acting stimulant antagonists for treating the medical problems associated with drug abuse and addiction. In addition, the antigen binding fragments (Fab) and other small molecular fragments of these monoclonal antibodies can serve as a shorter acting stimulant antagonist for treating medical problems like drug overdose. Knowledge gained from basic research into the neurobiology of drug abuse has led to major discoveries in medicine. Nevertheless, the development of medical strategies for treating the complex
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array of neurological problems associated with drug abuse has been frustratingly slow. In particular, development of medical treatments for alleviating the adverse psychosocial and health effects of d-methamphetamine and similar stimulants is badly needed. d-Methamphetamine-related hospital emergency cases across the U.S. increased 256% from 1991 to 1994 (1). The 1995 Toxic Exposure Surveillance System data showed there were 7,601 people treated in health care facilities for amphetamine-like drugs and other stimulants. This is particularly striking since during the same period there were only 3,440 cases of cocaine treatment and a total of 5,170 cases of all types of legal and illegal narcotics (including morphine, codeine and heroin). The current rise in dmethamphetamine use is also alarming because, unlike cocaine, it does not have to be imported. Even an amateur chemist can synthesize this drug in his home using easily obtained reagents and equipment. Web site: http://www.delphion.com/details?pn=US06669937__ •
Nasal delivery of apomorphine Inventor(s): Achari; Raja G. (Millington, NJ), Ahmed; Shamim (Central Islip, NY), Behl; Charanjit R. (Hauppauge, NY), deMeireles; Jorge C. (Syosset, NY), Liu; Tianquing (Central Islip, NY), Romeo; Vincent D. (late of Massapequa Park, NY), Sileno; Anthony P. (Brookhaven Hamlet, NY) Assignee(s): Nastech Pharmaceutical Company, Inc. (Bothell, WA) Patent Number: 6,740,660 Date filed: January 31, 2002 Abstract: Intranasal delivery methods and compositions for the delivery of dopamine receptor agonists are provided which are effective for the amelioration of erectile dysfunction in a mammal without causing substantial intolerable adverse side effects to the mammal. Nasally administered compositions for treating male erectile dysfunction in a mammal are also provided which include a therapeutically effective amount of a dopamine receptor agonist which has been dispersed in a system to improve its solubility and/or stability. Excerpt(s): The present invention relates generally to intranasal delivery methods and dosage forms. More particularly, methods and dosage forms for the safe and reliable intranasal delivery of apomorphine to ameliorate erectile dysfunction in a mammal are provided. Apomorphine is a potent dopamine receptor agonist which has a variety of uses. For example, it has been effectively used as an adjunctive medication in the treatment of Parkinson's disease which is complicated by motor fluctuations (T. van Laar et al., Arch. Neurol., 49: 482-484 (1992)). In particular, apomorphine has been used for relieving "off-period" symptoms in Parkinson patients with such response fluctuations. In the study by van Laar et al., the intranasally applied apomorphine used to achieve the results reportedly included an aqueous solution of apomorphine hydrochloride (HCL) at a concentration of 10 mg/ml. This formulation is also used for parenteral application and is published in different Pharmacopeia's. Also, U.S. Pat. No. 5,756,483 issued to Merkus (hereinafter "the '483 patent") which is hereby incorporated by reference, discloses the intranasal delivery of a variety of compositions, including apomorphine in combination with a cyclodextrin and/or a polysaccharide and/or a sugar alcohol for treating Parkinson's disease. The '483 patent, however, discloses very narrow dosage ranges of 0.1 to 2 mg of apomorphine per nostril which is specifically tailored for the amelioration of the "off-period" symptoms of Parkinson's disease.
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Web site: http://www.delphion.com/details?pn=US06740660__ •
Nucleic acid encoding Nematode dopamine transporter and the protein encoded thereby Inventor(s): Blakely; Randy D. (Brentwood, TN), Eppler; Cecil M. (Langhorne, PA) Assignee(s): American Cyanamid Company (Madison, NJ), Vanderbilt University (Nashville, TN) Patent Number: 6,596,512 Date filed: July 18, 2000 Abstract: A nematode dopamine tansporter cDNA has been cloned, sequenced, and expressed, and provides a convenient screening assay for antiparasitics, as well as psychoactive drugs. Excerpt(s): The nature of neuronal signaling is substantially similar in all animals, ranging from simple invertebrates to man. Neuronal signals take the form of electrical impulses, generated by a change in electrical potential across the plasma membrane and propagated along the characteristically extended neuron. Individual neurons, however, are separated by gaps known as synapses which present a barrier to neuronal signaling in its electrical form. At the synapse, the signal takes the form of a chemical message relayed by a group of small signaling molecules known as neurotransmitters. Many different types of neurotransmitters have been identified, including dopamine (DA), norepinephrine (NE),.gamma.-aminobutyric acid (GABA) and serotonin (5HT). Neurotransmitters are stored in synaptic vesicles located in the presynaptic terminals of nerve cells. Activation of a neuron results in the generation of an electrical signal which travels the length of the cell as an action potential until it reaches the presynaptic terminal. The change in membrane potential in the terminal causes synaptic vesicles to fuse with the nerve cell membrane, prompting the release of neurotransmitter into the synaptic cleft. After traversing the cleft by diffusion, neurotransmitter binds to highly selective receptors on the membrane of the postsynaptic neuron. The nature of the postsynaptic response is dictated by the particular neurotransmitter. Excitatory neurotransmitters cause depolarization of the postsynaptic cell membrane, triggering an action potential that recreates the signal electrically in the postsynaptic neuron. In contrast, inhibitory neurotransmitters suppress activation of the postsynaptic neuron by inhibiting the formation of an action potential. The extent of the signaling response is controlled by both the quantity of neurotransmitter released and the duration of its activity in the synapse. Many mechanisms ensure removal of the neurotransmitter from the synaptic cleft, including enzymatic destruction, active transport or reabsorption into the presynaptic neuron. Active transport is mediated by a class of transporter proteins, each specific to a particular type of neurotransmitter. Web site: http://www.delphion.com/details?pn=US06596512__
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Pharmaceutical composition for treating fecal incontinence Inventor(s): Kamm; Michael A. (London, GB), Phillips; Robin K. S. (Northwood, GB) Assignee(s): S.l.a. Pharma AG (Liestal, CH) Patent Number: 6,635,678 Date filed: August 24, 1999
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Abstract: Fecal incontinence and anal itch can be treated by administration, more particularly by local application to the anus, of an a adrenergic blocker, nitric oxide synthase inhibitor, prostaglandin F.sub.2.alpha., dopamine, morphine,.beta.-blockers, and 5-Hydroxytryptamine. The patients who benefit most from the invention are those who have a normal or low maximum anal resting pressure and a structurally intact internal anal sphincter muscle, and patients who have had major bowel resection and reanastomisis. Excerpt(s): This invention relates to the treatment of relief of fecal incontinence and anal itch (pruritis ani), particularly for patients who have had a major bowel resection and reanastomosis. Anal or fecal incontinence is the inability to voluntarily control the passage of feces or gas through the anus. It may occur either as fecal soiling or as rare episodes of incontinence for gas or watery stools. It is a very distressing condition that can result in self-inflicted social isolation and despair. Conventional treatments for fecal incontinence include drug therapy to improve stool consistency, such as morphine, loperamide and codeine phosphate to reduce gut motility, and laxatives to soften stools and relieve constipation. Biofeedback training is another treatment which involves muscle strengthening exercises to improve anal canal resting pressure, and squeeze pressure, and to teach symmetry of anal canal function. The most common form of treatment however, is surgical repair, such as the creation of a neo-sphincter which involves grafting on muscle from other parts of the anus, or a colostomy. (Gastroenterology in Practice, Summer 1995, p18-21; Dig Dis 1990; 8:179-188; and The New England Journal of Medicine, April 1992, p1002-1004). In mild cases of anal leakage, the patient will often try and plug the anus with a ball of cotton wall. Web site: http://www.delphion.com/details?pn=US06635678__ •
Pharmaceutical compositions for treating and/or preventing CNS disorders Inventor(s): Bhatti; Balwinder Singh (Winston-Salem, NC), Caldwell; William Scott (Winston-Salem, NC), Crooks; Peter Anthony (Lexington, KY), Deo; Niranjan Madhukar (Cincinnati, OH), Dull; Gary Maurice (Lewisville, NC), Ravard; Alain (Petit-Courone, FR) Assignee(s): Targacept, Inc. (Winston-Salem, NC) Patent Number: 6,624,173 Date filed: June 30, 1997 Abstract: Patients susceptible to or suffering from disorders, such as central nervous system disorders, which are characterized by an alteration in normal neurotransmitter release, such as dopamine release (e.g., Parkinsonism, Parkinson's Disease, Tourette's Syndrome, attention deficient disorder, or schizophrenia) are treated by administering an endo or exo form of a 1-aza-2-(3-pyridyl)bicyclo[2.2.1]heptane, a 1-aza-2-(3pyridyl)bicyclo [2.2.2]octane, a 1-aza-2-(3-pyridyl)bicyclo[3.2.2]nonane, a 1-aza-7-(3pyridyl) bicyclo[2.2.1]heptane, a 1-aza-3-(3-pyridyl)bicyclo[3.2.2]nonane, or a 1-aza-7-(3pyridyl)bicyclo[3.2.2]nonane. Excerpt(s): The present invention relates to pharmaceutical compositions, and particularly pharmaceutical compositions incorporating compounds which are capable of affecting nicotinic cholinergic receptors. The present invention also relates to methods for treating a wide variety of conditions and disorders, and particularly conditions and disorders associated with dysfunction of the central and autonomic nervous systems. Nicotine has been proposed to have a number of pharmacological effects. See, for
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example, Pullan et al. N. Engl. J. Med. 330:811-815 (1994). Certain of those effects may be related to effects upon neurotransmitter release. See for example, Sjak-shie et al., Brain Res. 624:295 (1993), where neuroprotective effects of nicotine are proposed. Release of acetylcholine and dopamine by neurons upon administration of nicotine has been reported by Rowell et al., J. Neurochem. 43:1593 (1984); Rapier et al., J. Neurochem. 50:1123 (1988); Sandor et al., Brain Res. 567:313 (1991) and Vizi, Br. J. Pharmacol. 47:765 (1973). Release of norepinephrine by neurons upon administration of nicotine has been reported by Hall et al., Biochem. Pharmacol. 21:1829 (1972). Release of serotonin by neurons upon administration of nicotine has been reported by Hery et al., Arch. Int. Pharmacodyn. Ther. 296:91 (1977). Release of glutamate by neurons upon administration of nicotine has been reported by Toth et al., Neurochem Res. 17:265 (1992). In addition, nicotine reportedly potentiates the pharmacological behavior of certain pharmaceutical compositions used for the treatment of certain CNS disorders. See, Sanberg et al., Pharmacol. Biochem. & Behavior 46:303 (1993); Harsing et al., J. Neurochem. 59:48 (1993) and Hughes, Proceedings from Intl. Symp. Nic. S40 (1994). Furthermore, various other beneficial pharmacological effects of nicotine have been proposed. See, Decina et al., Biol. Psychiatry 28:502 (1990); Wagner et al., Pharmacopsychiatty 21:301 (1988); Pomerleau et al., Addictive Behaviors 9:265 (1984); Onaivi et al., Life Sci. 54(3):193 (1994) and Hamon, Trends in Pharmacol. Res. 15:36. Various nicotinic compounds have be-en reported as being useful for treating a wide variety of conditions and disorders. See, for example, Williams et al. DN&P 7(4):205-227 (1994), Arneric et al., CNS Drug Rev. 1(1):1-26 (1995), Arneric et al., Exp. Opin. Invest. Drugs 5(1):79-100 (1996), Bencherif et al., JPET 279:1413 (1996), Lippiello et al., JPET 279:1422 (1996), PCT WO 94/08992, PCT WO 96/31475, and U.S. Pat. No. 5,583,140 to Bencherif et al., U.S. Pat. No. 5,597,919 to Dull et al., and U.S. Pat. No. 5,604,231 to Smith et al. Nicotinic compounds are particularly useful for treating a wide variety of Central Nervous System (CNS) disorders. Web site: http://www.delphion.com/details?pn=US06624173__ •
Polyamine treatment of neurological disorders Inventor(s): Murphy; Michael A. (5619 Chelsea Ave., La Jolla, CA 92037) Assignee(s): None Reported Patent Number: 6,576,672 Date filed: February 23, 2000 Abstract: 2,3,2 Tetramine (3,7-diazanonane-1,9-diamine) is propounded for treatment of Parkingson's Disease and dementias characterized by mitochondrial damage in view of this compound's ability to completely neutralize the dopamine-depriving effect of MPTP in laboratory animals up to 12 hours post MPTP injection, and to retain partial protection at suboptimal tissue levels for up to 36 hours. The effect of injecting combinations of MPTP and/or reducing agents and/or xenobiotics and/or depigmenting agents on Dopamine, Norepinephrine, Serotonin and Epinephrine levels demonstrated that MPTP and MPP+ act as reducing agents that mobilize copper and calcium, and sequester iron, and that the vulnerability of dopamine to these types of neurotoxins and to xenobiotics and metals can be corrected by administration of 2,3,2 tetramine that appears to redistribute metals between diverse storage pools and free metals in cytosol and regulate receptor mediated events, among other antidotal effects analogous to those of some of the endogenous polyamines.
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Excerpt(s): This invention relates to the treatment of neurological disorders in mammalian subjects, and more specifically to the diagnosis and therapy of Parkinson's Disease, Olivopontine Cerebellar Atrophy, Alzheimer's Disease and Lou Gehrig's Disease. Parkinson's Disease is a degenerative disease of the nervous system which affects one person in fifty over fifty years of age and one person in twenty over seventy years of age, without gender or social bias. Described by James Parkinson in 1817, the shaking palsy is comprised of a triad of tremor at rest, muscular rigidity and slowness of movement. Accurate description of the disease during the period of the Industrial Revolution has prompted people to speculate that environmental exposure to toxic chemicals precipitates the disease. Exposure to manganese precipitated a Parkinsonian syndrome in miners which also includes schizophreniform behaviors. Some epidemiologic studies have found association between industrial exposure to copper, manganese and copper simultaneously with iron and the incidence of Parkinson's disease (Gorell J. M et al), between incidence of Parkinson's disease and blood mercury levels (Ngim C. H. et al) and with death rates from Parkinson's Disease and proximity to iron and copper related industrial processes (Rybicki B. A. et al). Xenobiotics, natural and man made insecticides have also been suggested as candidate agents because they precipitate on occasion motor disturbances in animals and man somewhat akin to Parkinsonism. Thus both inorganic and organic chemicals may contribute to the toxicity mechanism. Other types of Parkinsonism include post encephalitic, Wilson's Disease and Parkinsonism secondary to cerebrovascular accidents, space occupying lesions and drug induced. The disease is progressive though not in all cases. Dementia with Alzheimer type pathological changes follows but does not precede the development of Parkinson's Disease in about one quarter of diagnosed cases. Generalized wasting and anorexia also occur, metabolic components of the disease not attributable to hypothalamic (tuberoinfundibular) dopaminergic dysfunction. Web site: http://www.delphion.com/details?pn=US06576672__ •
Regulation of tyrosine hydroxylase Inventor(s): Alexi; Tajrena (Auckland, NZ), Gluckman; Peter D. (Auckland, NZ), Guan; Jian (Auckland, NZ) Assignee(s): Neuronz Limited (Auckland, NZ) Patent Number: 6,617,311 Date filed: February 12, 2001 Abstract: This invention relates to methods of regulating the effect of tyrosine hydroxylase (TH). In particular it relates to increasing the effective amount of TH in the central nervous systems (CNS) for the purpose of increasing TH-mediated dopamine production in the treatment of conditions such as Parkinson's disease. Excerpt(s): Parkinson's disease is the second most prevalent neurodegenerative disorder after Alzheimer's. It is a chronic and progressive motor system disorder and is distinguished by a tremor at rest, muscular rigidity, a slowness of movement initiation and movement execution and a mask-like appearance to the face. The cause of this disease is unknown but the symptoms are a consequence of an 80% or greater loss of the dopaminergic neurons (which produce dopamine) in the pars compacta region of the substantia nigra (SNc). Web site: http://www.delphion.com/details?pn=US06617311__
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Resolution of trans-7-(hydroxy-methyl)octa-hydro-2H-pyrido[1,2-a]pyrazine Inventor(s): Harms; Arthur E. (Niskayuna, NY) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,670,476 Date filed: November 13, 2001 Abstract: The invention provides a process for the optical resolution of a racemic mixture, or an optically enriched mixture, of trans-7-(hydroxymethyl)octa-hydro-2Hpyrido-1,2a)pyrazine, a key intermediate for preparing pharmacologically active 2,7substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives useful in the treatment of disorders of the dopamine system. The process of the invention involves use of D-(-) or L-(+)naproxen as a resolving agent. Excerpt(s): The present invention relates to a process for the optical resolution of a key intermediate for preparing pharmacologically active 2,7-substituted octahydro-1Hpyrido[1,2-a]pyrazine derivatives, such as (7S,trans)-2-(2-pyrimidinyl)-7(hydroxymethyl)octahydro-2H-pyrido(1,2-a)py razine, which are disclosed in U.S. Pat. No. 5,852,031, the contents of which are hereby incorporated by reference. These pyrazine compounds are ligands with specificity for dopamine receptor subtypes, especially the dopamine D4 receptor, within the animal body, and are therefore useful in the treatment of disorders of the dopamine system. The process of the present invention involves resolution of trans-7-(hydroxymethyl)octahydro-2H-pyrido(1,2a)pyrazine using D-(-) or L-(+)naproxen. Previously, the desirable optically resolved pyrazine compounds were obtained by later-stage resolution using D-(-) or L-(+)-tartaric acid, as disclosed in European Patent No. 569387. The present method has the advantage of minimizing material losses incurred by conducting resolutions after a multistep synthetic sequence, and results in a more efficient, higher-yielding process for preparing the (7S,trans)-2-(2-pyrimidinyl)-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)py razines. reacting the racemic mixture, or the optically enriched mixture, with (+)naproxen or (-)-naproxen to form, respectively, a diastereomeric mixture of the (+)- or ()-naproxen salts of each of the enantiomers; separating each of the diastereomeric (+)- or (-)-naproxen salts; and if desired, converting the respective naproxen salt of each enantiomer to the free base thereof. Web site: http://www.delphion.com/details?pn=US06670476__
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Tropane analogs and methods for inhibition of monoamine transport Inventor(s): Blundell; Paul (Winchester, MA), Chen; Zhengming (Woburn, MA), Madras; Bertha K. (Newton, MA), Meltzer; Peter C. (Lexington, MA) Assignee(s): Organix, Inc. (Woburn, MA), President and Fellows of Harvard College (Cambridge, MA) Patent Number: 6,670,375 Date filed: June 6, 2001 Abstract: New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7-substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure Senantiomers. Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic
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compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter. Excerpt(s): This invention relates to tropane analogs of cocaine and their use as inhibitors of monoamine reuptake. Cocaine dependence is a problem of national significance. To date no cocaine pharmacotherapy has been reported. Cocaine is a potent stimulant of the mammalian central nervous system. Its reinforcing properties and stimulant effects are associated with its propensity to bind to monoamine transporters, particularly the dopamine transporter (DAT). (Kennedy, L. T. and I. Hanbauer (1983), J. Neurochem. 34: 1137-1144; Kuhar, M. J., M. C. Ritz and J. W. Boja (1991), Trends Neurosci. 14: 299-302; Madras, B. K., M. A. Fahey, J. Bergman, D. R. Canfield and R. D. Spealman (1989), J. Pharmacol. Exp. Ther. 251: 131-141; Madras, B. K., J. B. Kamien, M. Fahey, D. Canfield, et al. (1990), Pharmacol Biochem. Behav. 35: 949-953; Reith, M. E. A., B. E. Meisler, H. Sershen and A. Lajtha (1986), Biochem. Pharmacol. 35: 1123-1129; Ritz, M. C., R. J. Lamb, S. R. Goldberg and M. J. Kuhar (1987), Science 237: 1219-1223; Schoemaker, H., C. Pimoule, S. Arbilla, B. Scatton, F. Javoy-Agid and S. Z. Langer (1985), Naunyn-Schmiedeberg's Arch. Pharmacol. 329: 227-235.) It also binds with substantial potency to serotonin transporters (SERT) and norepinephrine transporters. Also, only the R-enantiomers of cocaine have been found active in a variety of biological and neurochemical measures. (Clarke, R. L., S. J. Daum, A. J. Gambino, M. D. Aceto, et al. (1973), J. Med. Chem. 16: 1250-1267; Kaufman, M. J. and B. K. Madras (1992), Synapse 12: 99-111; Madras, B. K., M. A. Fahey, J. Bergman, D. R. Canfield and R. D. Spealman (1989), J. Pharmacol. Exp. Ther. 251: 131-141; Madras, B. K., R. D. Spealman, M. A. Fahey, J. L. Neumeyer, J. K. Saha and R. A. Milius (1989), Mol. Pharmacol. 36: 518-524; Reith, M. E. A., B. E. Meisler, H. Sershen and A. Lajtha (1986), Biochem. Pharmacol. 35: 1123-1129; Ritz, M. C., R. J. Lamb, S. R. Goldberg and M. J. Kuhar (1987), Science 237: 1219-1223; Sershen, H., M. E. A. Reith and A. Lajtha (1980), Neuropharmacology 19: 1145-1148; Sershen, H., M. E. A. Reith and A. Lajtha (1982), Neuropharmacology 21: 469474; Spealman, R. D., R. T. Kelleher and S. R. Goldberg (1983), J. Pharmacol. Exp. Ther. 225: 509-513.) Parallel stereoselective behavioral effects have also been observed. (Bergman, J., B. K. Madras, S. E. Johnson and R. D. Spealman (1989), J. Pharmacol. Exp. Ther. 251: 150-155; Heikkila, R. E., L. Manzino and F. S. Cabbat (1981), Subst. Alcohol Actions/Misuse 2: 115-121; Reith, M. E. A., B. E. Meisler, H. Sershen and A. Lajtha (1986), Biochem. Pharmacol. 35: 1123-1129; Spealman, R. D., R. T. Kelleher and S. R. Goldberg (1983), J. Pharmacol. Exp. Ther. 225: 509-513; Wang, S., Y. Gai, M. Laruelle, R. M. Baldwin, B. E. Scanlet, R. B. Innis and J. L. Neumeyer (1993), J. Med. Chem. 36: 19141917.) For example, in primates and rodents the stimulating and reinforcing properties of the (-)-enantiomer of cocaine or its 3-aryltropane analogs were considerably greater than for the (+)-enantiomers. Web site: http://www.delphion.com/details?pn=US06670375__
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Use of dopamine receptor antagonists in palliative tumor therapy Inventor(s): Engel; Jurgen (Alzenau, DE), Hilgard; Peter (Frankfurt, DE), Klenner; Thomas (Ingelheim, DE), Nickel; Bernd (Muhltal, DE) Assignee(s): Zentaris AG (Frankfurt am Main, DE) Patent Number: 6,576,624 Date filed: June 23, 2000 Abstract: The side effect of decrease in body weight caused by the alkylphosphocholines such as miltefosine can be antagonized by certain acetylcholine receptor antagonists such as domperidone and pimozide. The combination of alkylphosphocholine plus the antagonist does not have any effect on the anti-tumor action of the alkylphosphocholine. The combination also caused no new side effects in the animals. Excerpt(s): The invention relates to the use of dopamine receptor antagonists in palliative tumor therapy, particularly as agents for antagonizing side effects such as are frequently observed in tumor therapy by means of alkylphosphocholines, particularly miltefosine. It is known and described that the alkylphosphocholine miltefosine causes side effects in patients during the treatment of cancer. These also manifest themselves in patients treated with miltefosine by a marked loss of body weight (Eur. J. Cancer, Vol. 29 A, No. 2, pp. 208-209, 1993). Further side effects of the chemotherapy are: damage to the tissue with a high proliferation rate, leuko- and thrombopenia, decrease in erythrocytes, gastrointestinal disorders, loss of appetite, upper abdominal complaints, disturbed absorption and diarrhea, as well as loss of hair and also liver damage and hyperuricaemia. In a dose-finding study by J. Verweij et al. (J. Cancer Res. Clin. Oncol 118:606-608 (1992)), it was observed that most antiemetics (including 5HT.sub.3 antagonists) were inactive in the prevention of vomiting and nausea. The smallest emetic effect was achieved if miltefosine was taken immediately after eating, domperidone being given 0.5 hours before eating in a dose of 20 mg. In the phase II studies of the same author which were carried out later (Eur. J. Cancer Vol. 29 A, No. 5 p. 779(1993), it was meanwhile found that it was not possible to prevent vomiting either by standard antiemetics or by 5HT.sub.3 antagonists. Web site: http://www.delphion.com/details?pn=US06576624__
Patent Applications on Dopamine As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to dopamine:
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(-)-1-(3,4-DichlorophenyI)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as a dopamine-reuptake inhibitor Inventor(s): Epstein, Joseph William; (Monroe, NY), Lippa, Arnold Stan; (Ridgewood, NJ) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030181508 Date filed: April 29, 2003 Abstract: The present invention relates to (-)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable salts thereof, compositions comprising (-)1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof, and methods for treating or preventing a disorder alleviated by inhibiting dopamine reuptake. In one embodiment, the disorder is attention-deficit disorder, depression, obesity, Parkinson's disease, a tic disorder, or an addictive disorder. The (-)1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is preferably substantially free of its corresponding (+)-enantiomer. Excerpt(s): The present invention relates to (-)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable salts thereof, compositions comprising (-)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hex- ane or a pharmaceutically acceptable salt thereof and methods for treating or preventing a disorder alleviated by inhibiting dopamine reuptake comprising administering to a patient (-)-1-(3,4dichlorophenyl)-3-azabic- yclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof. Dopamine is a monoamine neurotransmitter that plays a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of dopamine neurotransmission is through reuptake of released dopamine by Na.sup.+/Cl.sup.--dependent plasma membrane transporters (Hoffman et al., 1998, Front. Neuroendocrinol. 19(3):187-231). Depending on the surrounding ionic conditions, the dopamine transporter can function as a mediator of both inward directed dopamine transport (i.e., "reuptake") and outward directed dopamine transport (i.e., "release"). The functional significance of the dopamine transporter is its regulation of dopamine neurotransmission by terminating the action of dopamine in a synapse via reuptake (Hitri et al., 1994, Clin. Pharmacol. 17:1-22). Attention deficit disorder is a learning disorder involving developmentally inappropriate inattention with or without hyperactivity. The primary signs of attention deficit disorder are a patient's inattention and impulsivity. Inappropriate inattention causes increased rates of activity or reluctance to participate or respond. A patient suffering from attention deficit disorder exhibits a consistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. (See, e.g., U.S. Pat. No. 6,121,261 to Glatt et al.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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(S)-4-amino-5-chloro-2-methoxy-N-[1-[1-(2-tetrahydrofuryl-carbonyl)-4-piperidinylmethyl]-4-piperidinyl]benzamide, process for the preparation thereof, pharmaceutical composition containing the same, and intermediate therefor Inventor(s): Hirokawa, Yoshimi; (Ikoma-shi, JP), Kan, Yoko; (Suita-shi, JP), Kato, Shiro; (Sakai-shi, JP), Morikage, Kazuo; (Suita-shi, JP), Morikage, Yukiko; (Suita-shi, JP), Yamazaki, Hiroshi; (Suita-shi, JP), Yoshida, Naoyuki; (Sakai-shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030216433 Date filed: December 18, 2002 Abstract: (S)-4-Amino-5-chloro-2-methoxy-N-[-[1 -(2-tetrahydrofurylcarbonyl)-4-piperidinylmethyl]-4-piperidinyl]benzamide of the following formula (I): 1or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, and a process for preparing the same, a pharmaceutical composition containing the same, and intermediate therefor.The compound of the present invention is useful as a gastrointestinal motility enhancer or a gastrointestinal prokinetic agent, which shows a potent affinity for 5-HT.sub.4 receptor, and shows few effects on the heart, and further shows few side effects on the central nervous system based on the dopamine D.sub.2 receptor. Excerpt(s): The present invention relates to a novel (S)-4-amino-5-chloro-2-met- hoxy-N[1-[1-(2-tetrahydrofurylcarbonyl)-4-piperidinylmethyl]-4-piperidinyl]benzamide exhibiting a potent gastrointestinal motility enhancing effect based on its agonistic activity on serotonin 4 receptor (hereinafter, occasionally referred to as 5-HT.sub.4 receptor) and having few effects on the heart. Said compound is an amide compound of 4-amino-5-chloro-2-methoxybenzoic acid. The present invention also relates to a process for the preparation of said compound, a pharmaceutical composition containing said compound, and an intermediate therefor. R.sup.11 is a hydrogen atom, a lower alkyl group, a cycloalkyl group, etc., provided that (1) when q is 0, then Z is --CH.sub.2--, etc.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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1-Phenyl-4-benzylpiperazines dopamine receptor subtype specific ligands Inventor(s): Chen, Xi; (Clinton, CT), Thurkauf, Andrew; (Danbury, CT) Correspondence: Steven J. Sarussi; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20040083447 Date filed: September 22, 2003 Abstract: Disclosed are compounds of the formula: 1or the pharmaceutically acceptable addition salts thereof wherein:R.sub.1 is halogen or C.sub.1-C.sub.4 alkyl; andR.sub.2 and R.sub.3 are the same or different and represent hydrogen, halogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, alkylthio, hydroxy, amino, mono(C.sub.1C.sub.4)alkylamino, di(C.sub.1-C.sub.4)alkyl- amino, orR.sub.2 and R.sub.3 together represent a 4 carbon alkenylene moiety that together with the phenyl ring to which they are attached form a naphthyl moiety,which compounds are useful in the treatment of neuropsycological diseases such as schizophrenia, psychotic depression and mania.
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Excerpt(s): This invention relates to certain 1-phenyl-4-benzylpiperazines and pharmaceutical compositions containing them. It also relates to the use of such compounds in the treatment or prevention of psychotic disorders such as schizophrenia and other central nervous system diseases. The use of the compounds of this invention to the treatment of these disorders is indicated by the ability of the compounds to bind selectively to dopamine receptor subtypes. The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D2 receptors in the striatal region of the brain. The dopamine D4 receptor subtype has recently been identified (Van Tol, H. H. et al., Nature, 1991, 350, 610). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics suggest that the D4 receptor play a role in the etiology of schizophrenia Selective D4 antagonists are effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics. Since dopamine D4 receptors are concentrated in the limbic system which controls cognition and emotion, compounds which interact with these receptors have utility in the treatment of cognitive disorders. Such disorders include the cognitive deficits which are a significant component of the negative symptoms (social withdrawal and unresponsiveness) of schizophrenia. Other disorders involving memory impairment or attention deficit disorders can also be treated with compounds that interact specifically with the dopamine D4 receptor subtype. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
4-Substituted piperidines, and methods of use thereof Inventor(s): Radeke, Heike; (South Grafton, MA), Shao, Liming; (Lincoln, MA) Correspondence: Foley Hoag, Llp; Patent Group, World Trade Center West; 155 Seaport Blvd; Boston; MA; 02110; US Patent Application Number: 20030236283 Date filed: December 11, 2002 Abstract: One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters. Excerpt(s): This application claims the benefit of priority under 35 USC.sctn. 119(e) to U.S. Provisional Patent Application serial No. 60/339,506, filed Dec. 11, 2001. Dopamine, norepinephrine and serotonin are mammalian monoamine neurotransmitters that play important roles in a wide variety of physiological processes. Therefore, compounds that selectively modulate the activity of these three neurotransmitters, either individually, in pairs, or as a group, promise to serve as agents effective in the treatment of a wide range
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of maladies, conditions and diseases that afflict mammals due to atypical activities of these neurotransmitters. For example, depression is believed to result from dysfunction in the noradrenergic, dopaminergic, or serotonergic systems. Furthermore, the noradrenergic system appears to be associated with increased drive, whereas the serotonergic system relates more to changes in mood. Therefore, it is possible that the different symptoms of depression may benefit from drugs acting mainly on one or the other of these neurotransmitter systems. On the other hand, a single compound that selectively affects both the noradrenergic and serotonergic systems should prove effective in the treatment of depression comprising symptoms related to dysfunction in both systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
8'4-'3-(5Fluoro-1h-indol-3yl)propyl!-1-piperazinyl!-2-methyl-2h-1,4-benzoxazin3(4h)-one methanesulfonate with high affinity for the dopamine d2 receptor and the seotonix reuptake site Inventor(s): Bakker, Cornelis; (Weesp, NL) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040024207 Date filed: May 22, 2003 Abstract: The invention relates to the novel mesylate of a phenylpiperazine derivative of the formula (I). This salt has favourable properties as compared with the free base of this compound. 1 Excerpt(s): Patent application No. PCT/EP 00/08090 (not yet published) relates a group of novel phenyl piperazines. The compounds of that group show high affinity for both the dopamine D.sub.2 receptor and the serotonin reuptake site. This combination is useful for the treatment of schizophrenia and other psychotic disorders which enables a more complete treatment of all disease symptoms (e.g. positive symptoms and negative symptoms). The compounds show activity as antagonists at dopamine D.sub.2 receptors as they potentially antagonize apomorphine-induced climbing behaviour in mice. The compounds also show activity as inhibitors of serotonin reuptake, as they potentiate 5HTP induced behaviour in mice. The compounds are active in therapeutic models sensitive to clinically relevant antipsychotics (e.g. the conditioned avoidance response; Van der Heyden & Bradford, Behav. Brain Res., 1988, 31:61-67) and antidepressants or anxiolytics (e.g. suppression of stress-induced vocalization; van der Poel et al., Psychopharmacology, 1989, 97: 147-148). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Acylamino cyclopropane derivatives Inventor(s): Fliri, Anton F. J.; (Stonington, CT), Reinhold, Anthony R.; (Mystic, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20040029876 Date filed: July 29, 2003
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Abstract: This invention relates to novel acylamino cyclopropane derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as modulators of dopamine D3 receptors and for the treatment of anxiety, psychosis, substance abuse, Parkinson's disease, sexual dysfunction, and other central nervous system disorders. Excerpt(s): The present invention relates to novel acylamino cyclopropane derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as modulators of dopamine D3 receptors and for the treatment of anxiety, psychosis, substance abuse, Parkinsons disease, sexual dysfunction, and other central nervous system disorders. The dopamine D3 receptor (the "D3 receptor") subtype has been identified (Sokoloff, P. et al., Nature, 1990, 347, 146). The D3 receptor is preferentially expressed in limbic brain regions such as the septal area and amygdala (Landwehrmeyer et al., Mol. Brain Res. (1993), 18 (1-2), 187-92). These regions are thought to be important brain areas for the regulation of cognition, motivation and emotion (Graeff et al., Braz. J. Med. Biol. Res. (1994), 27(10), 2453-6). The unique localization of D3 receptors and their differential recognition of various antipsychotics suggest that such receptors may play a major role in the etiology of schizophrenia. Moreover, in patients suffering from Parkinson's disease (PD), repeated administration of levodopa, a dopamine precursor, results in progressive resumption of motor performances as well as in development of abnormal involuntary movements, suggesting sensitization to the drug. In a rat model of PD, it was shown that the unexpected appearance of the dopamine D3 receptor in the denervated caudate putamen, an area from which it is normally absent, accounts for the sensitization process: sensitization occurs and declines with the same time course and sensitization is blocked by a preferential D3 receptor antagonist; suggesting that dopamine D3 receptor antagonists may be useful in therapy of PD. Biomed. Health Res. (2000), 26, "Molecular Biology Approach to Parkinson's Disease", edited by Jenner, P., 49-60. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Aryl and heteroaryl substituted tetrahydroisoquinolines and use thereof Inventor(s): Beck, James P.; (Kalamazoo, MI), Curry, Matt A.; (Coatesville, PA), Smith, Mark A.; (Landenberg, PA) Correspondence: Michael L. Goldman; Nixon Peabody Llp; Clinton Square; P.O. Box 31051; Rochester; NY; 14603-1051; US Patent Application Number: 20030203920 Date filed: April 29, 2003 Abstract: Provided herein are compounds of the formula (I): 1wherein R.sup.1-R.sup.8 are as described herein, R.sup.4 being aryl or heteroaryl Such compounds are particularly useful in the treatment of a disorder which is created by or is dependent upon decreased availability of serotonin, norepinephrine or dopamine. Excerpt(s): The present invention relates to compounds, compositions, methods for the treatment of various neurological and psychological disorders, and the use of the compounds in combination therapy. In particular, the present invention relates to such compounds, compositions and methods wherein the compounds are novel 4-phenyl substituted tetrahydroisoquinolines derivatives. Serotonin, dopamine and norepinephrine are known to be important chemical messengers participating in the transmission of nerve impulses in the brain. These messengers are liberated at specific
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sites on pre-synaptic cells and received, to complete transmission of the impulse, at specific sites on post-synaptic cells. Their effect is then terminated by metabolism or by uptake into the pre-synaptic cells. Drugs capable of blocking the pre-synaptosomal uptake of either of these chemical messengers in the brain, are useful in alleviating disorders associated with decreased levels of these chemical messengers. For example, duloxetine and fluoxetine which are known serotonin reuptake inhibitors have been found to be useful in the treatment of depression, obesity and obsessive-compulsive disease (Wong, et al., U.S. Pat. No. 5,532,244). Also, Moldt, et al., U.S. Pat. No. 5,444,070, discloses the use of dopamine reuptake inhibitors in the treatment of depression, Parkinsonism, drug addiction and/or abuse, cocaine and/or amphetamine addiction and/or abuse. Freedman, et al., U.S. Pat. No. 6,136,803 also discloses synaptic norepinephrine or serotonin uptake inhibitors which are useful in treating depression in a patient. Furthermore, Norden, U.S. Pat. No. 5,789,449 discloses the use of serotonin reuptake inhibitors in treating psychiatric symptoms consisting of anger, rejection sensitivity, and lack of mental or physical energy. Also, Foster, et al., U.S. Pat. No. 4,902,710, discloses the use of serotonin and norepinephrine uptake inhibitors in suppressing the desire of humans to smoke or consume alcohol. Thus, there continues to remain a need to develop novel compounds which block reuptake of norephinephrine, dopamine or serotonin. Compounds which inhibit the reuptake of serotonin or norephinephrine, have also been used in combination therapy. For example, Glatt, et al., U.S. Pat. No. 6,121,261 discloses the use of selective serotonin reuptake inhibitors or norephinephrine uptake inhibitiors, in combination with neurokinin-1 receptor antagonist for treating attention deficit disorder in a patient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Chromenone derivatives and their use for treating diseases in conjunction with 5hta1receptors and/or dopamine d2 receptors Inventor(s): Ackermann, Karl-Augst; (Ober-Ramstadt, DE), Bartoszyk, Gerd; (Weiterstadt, DE), Gottschlich, Rudolf; ( Reinheim, DE), Prucher, Helmut; (Heppenheim, DE), Seyfried, Christoph; (Seeheim, DE), Van Amsterdam, Christoph; (Darmstadt, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040014768 Date filed: February 21, 2003 Abstract: Novel chromenone derivatives of the formula I 1in which Y, X, R.sup.1, R.sup.2, R.sup.3 and n are as defined in claim 1, as inhibitors of the 5-HT.sub.1A receptor and of the dopamine D.sub.2 receptor. Excerpt(s): and their physiologically acceptable salts and solvates. Partially similar compounds are disclosed in EP 0 584 091. The invention had the object of finding novel compounds having valuable properties, in particular those which can be used for the production of medicaments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combination immediate release sustained release levodopa/carbidopa dosage forms Inventor(s): Han, Chien-Hsuan; (Sunnyvale, CA), Hsiao, Charles; (Pleasanton, CA), Hsu, Larry; (Santa Clara, CA), Ting, Richard; (Newark, CA) Correspondence: Kendrew Colton; Registered Patent Attorney; Fitch, Even, Tabin And Flannery; 1801 K Street, NW., Suite 401l; Washington; DC; 20006-1201; US Patent Application Number: 20030224045 Date filed: May 29, 2002 Abstract: Dosage forms containing both immediate release and sustained release components for the treatment of ailments associated with depleted amounts of dopamine in brain tissue of a patient. The dosage forms contain a combination of carbidopa and levodopa. Excerpt(s): The present invention relates to dosage forms comprising both immediate release and sustained release components comprising a combination of carbidopa and levodopa for the treatment of ailments associated with depleted amounts of dopamine in a patients brain tissue. Combinations of carbidopa and levodopa to treat Parkinsons disease are known in the pharmaceutical arts. Several products currently on the North American market, including SINEMET.RTM. and SINEMET.RTM. CR contain combinations of carbidopa and levodopa in immediate release and controlled release forms respectively. The carbidopa and levodopa combination are used to treat the symptoms of Parkisons disease which is characterized by abnormally low levels of dopamine. Dopamine is a neurotransmitter having significant influence over the mobility and control of the skeletal muscular system. Patients suffering from Parkinsons disease frequently have periods in which their mobility becomes difficult often resulting in an inability to move. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Composition comprising cocoa Inventor(s): Raggers, Rene John; (Amsterdam, NL), Ter Laak, Wies; (Amsterdam, NL), Verdegem, Peter Julien Edward; (Zetten, NL) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20040005347 Date filed: June 30, 2003 Abstract: The invention pertains to a composition and a method for the treatment of mood disorders, in particular of treating, preventing or alleviate depression, mood disorders or insufficient mood, obesity, overweight, premenstrual syndrome, craving, carbohydrate craving, chocolate craving, menopausal complaints, erectile dysfunction and/or reduced libido. The composition contains cocoa or one or more of its pharmacologically active components, and a dopamine D2 receptor agonist. Excerpt(s): The invention concerns nutritional and pharmaceutical compositions containing cocoa components for improving mood. Cocoa and chocolate comprise several advantageous pharmacologically active components, and have therefore, knowingly or unknowingly, been used to alleviate or treat certain disorders. There remains a vast interest for compositions which induce the pharmacological effects of cocoa or chocolate, however which do not have the adverse side effect induced by
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chocolate and/or cocoa or, one or more of its pharmacological components. Products available within the art, which provide the advantageous effects of the pharmacological compounds within the cocoa/chocolate, appeared insufficient. Many cocoa-containing products have high fat or carbohydrate content causing obesity and overweight. Alternatives to these products include diet and low fat products, such as low fat cocoa powder, cocoa extracts and the like. Pharmacological compounds within cocoa or chocolate have been used in products providing appetite suppression and mood improvement. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for modulation of DARPP-32 phosphorylation Inventor(s): Greengard, Paul; (New York, NY), Rakhilin, Sergey V.; (Yorktown, NY), Starkova, Natalia; (New York, NY), Svenningsson, Per; (New York, NY) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030171255 Date filed: August 12, 2002 Abstract: The present invention provides methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The invention provides methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The invention provides methods of treating serotonergic intracellular signaling pathway disorders, e.g., depression. The invention provides methods of treating dopaminerelated disorders. The invention provides methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1, cyclin-dependent kinase 5, AMPA receptors, protein phosphatase-1, protein phosphatase 2C, protein phosphatase 2B and/or protein phosphatase 2A, for use in such treatments. The invention also provides methods of modulating phosphorylation-dependent activation of AMPA receptors for use in such treatments. Excerpt(s): This application claims benefit, under 35 U.S.C.sctn.119(e), of U.S. provisional application No. 60/311,641, filed on Aug. 10, 2001, which is incorporated herein by reference in its entirety. The present invention relates to methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The present invention relates to methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclindependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The present invention relates to methods of treating serotonergic intracellular signaling pathway disorders, e.g., depression. The present invention also relates to methods of treating dopamine-related disorders. The present invention relates to methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A), for use in such treatments. The present invention also relates to methods of modulating phosphorylation-dependent activation of AMPA receptors for
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use in such treatments. Depression is among the most debilitating psychiatric disorders, yet few pharmacological approaches exist for treating depression. Tricyclic antidepressants, which inhibit serotonin and noradrenaline reuptake transporters, and monoamine oxidase inhibitors, which inhibit the major catabolic enzyme for monoamine neurotransmitters, have been available for over 50 years. Another treatment strategy that has been utilized for many years is electroconvulsive seizure therapy. More recently, selective serotonin reuptake inhibitors have been developed. Nevertheless, today's treatments are sub-optimal, with only approximately 50% of all patients demonstrating complete remission, although more (up to 80%) show partial responses (Nestler et al., 2002; Neuron 34, 13-25). There therefore exists an urgent need for novel strategies for the treatment of depression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Derivatives of 2-aminotetralins and pharmaceutical analogs thereof exhibiting differentail cns receptor activity and behavior Inventor(s): Dutta, Aloke K; (Novi, MI) Correspondence: Brooks & Kushman P.C.; 1000 Town Center; Twenty-second Floor; Southfield; MI; 48075; US Patent Application Number: 20030225154 Date filed: April 21, 2003 Abstract: Aminotetralin derivatives and pharmacological analogs thereof which contain an N-propynyl group exhibit differential dopaminergenic receptor activity. The subject compounds are useful in affecting dopamine receptor activity, particularly in exhibiting differing activity among the various dopamine receptor subtypes. The compounds are useful in treating CNS disorders in mammals in general, and humans in particular. Excerpt(s): The present invention pertains to novel organic compounds which exhibit differential CNS activity, in particular differential dopaminergenic behavior, and to the treatment of central nervous system (CNS) disorders by administering such compounds or a pharmaceutically acceptable salt or derivative thereof to a mammal in need of such treatment. The importance of dopamine in CNS activity is well recognized, and dopamine receptors have been important targets for drug development. O. Civelli et al., "Molecular Diversity of the Dopamine Receptors", ANNU. REV. PHARMACOL. TOXICOL. 32, 281-307, 1993; P. Seeman et al., "Dopamine Receptor Pharmacology", TIPS, 15, 264-270, 1994. Detailed investigation has recently revealed the existence of several subtypes of dopamine ("DA") receptors. See Civelli, op. cit., Seeman, op. cit., and J. W. Kebabian et al., "Multiple Receptors for Dopamine", NATURE, 277, 93-96, 1979. From cloning of DA receptor forms and isoforms, two main D1-like (D1 and D5) and D2-like (D2, D3, and D4) categories of DA receptors can be identified. Civelli, op. cit., Seeman, op. cit. Of the receptor subtypes, the D3 receptor is distributed in the limbic area of the human brain, but absent from the caudate and putamen. This distribution makes the D3 receptor a potential target for drugs with an unusual spectrum of activities, in particular, CNS activities focused on specific disorders. For example, D3 antagonists may exhibit activity as atypical antipsychotic agents. D3 agonists have potential application in the therapeutic treatment for Parkinson's disease. B. Giros et al., ACAD. SCI [III] 1990, 311, 501. Recent studies suggest that D3 specific compounds may be useful in treating cocaine addition. S. G. Caine et al., "Modulation of Cocaine Selfadministration in the Rat through D-3 Dopamine Receptors", SCIENCE, 260, 1914-1816, 1993; S. B. Caine et al., "Pretreatment With The Dopamine Agonist 7-OH-DPAT Shifts
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the Cocaine Self-administration Dose Effect Function to the Left Under Different Schedules in the Rat", BEHAV. PHARMACOL. 6, 33-347, 1995; D. B. Calne et al., "Therapeutics and Neurology", BLACKWELL SCIENTIFIC PUBLICATIONS, Oxford, 1980. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Dopamine agonist formulations for enhanced central nervous system delivery Inventor(s): Quay, Steven C.; (Edmonds, WA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20040028613 Date filed: June 25, 2001 Abstract: Pharmaceutical formulations are described comprising at least one dopamine receptor agonist and one or more mucosal delivery-enhancing agents for enhanced mucosal delivery of the dopamine receptor agonist. In one aspect, the mucosal delivery formulations and methods provide enhanced delivery of the dopamine receptor agonist to the central nervous sytstem (CNS), for example by yielding dopamine receptor agonist concentrations in the cerebral spinal fluid of 5% or greater of the peak dopamine agonist concentrations in the blood plasma following administration to a mammalian subject. Exemplary formulations and methods within the invention utilize apomorphine as the dopamine receptor agonist. Other exemplary methods and formulations focus in intranasal administration of a dopamine receptor agonist. The formulations and methods of the invention are useful for treating a variety of diseases and conditions in mammalian subjects, including Parkinson's disease, male erectile dysfunction, female sexual dysfunction, among others. In alternate aspects, the mucosal delivery formulations and methods of the invention include one, or any combination of, mucosal delivery-enhancing agents selected from (a) aggregation inhibitory agents; (b) charge modifying agents; (c) pH control agents; (d) degradative enzyme inhibitors; (e) mucolytic or mucus clearing agents; (f) ciliostatic agents; (g) membrane penetrationenhancing agents; (h) modulatory agents of epithelial junction physiology; (i) vasodilator agents; (j) selective transport-enhancing agents; and (k) stabilizing delivery vehicles, carriers, supports or complex-forming agents. These methods and formulations of the invention provide for significantly enhanced absorption of dopamine receptor agonists into or across a nasal mucosal barrier to a target site of action, for example the CNS. Excerpt(s): A major disadvantage of drug administration by injection is that trained personnel are often required to administer the drug. For self-administered drugs, many patients are reluctant or unable to give themselves injections on a regular basis. Injection is also associated with increased risks of infection. Other disadvantages of drug injection include variability of delivery results between individuals, as well as unpredictable intensity and duration of drug action. Despite these noted disadvantages, injection remains the only approved delivery mode for a large assemblage of important therapeutic compounds. These include conventional drugs, as well as a rapidly expanding list of peptide and protein biotherapeutics. Delivery of these compounds via alternate routes of administration, for example, oral, nasal and other mucosal routes, often yields variable results and adverse side effects, and fails to provide suitable bioavailabilty. For macromolecular species in particular, especially peptide and protein therapeutics, alternate routes of administration are limited by susceptibility to
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inactivation and poor absorption across mucosal barriers. Mucosal administration of therapeutic compounds may offer certain advantages over injection and other modes of administration, for example in terms of convenience and speed of delivery, as well as by reducing or elimination compliance problems and side effects that attend delivery by injection. However, mucosal delivery is limited of biologically active agents is limited by mucosal barrier functions and other factors. For these reasons, mucosal drug administration typically requires larger amounts of drug than administration by injection. Other therapeutic compounds, including large molecule drugs, peptides and proteins, are often refractory to mucosal delivery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Imaging agents for diagnosis of parkinson's disease Inventor(s): Babich, John W.; (North Scituate, MA), Smith, Miles P.; (Belmont, MA) Correspondence: Foley Hoag, Llp; Patent Group, World Trade Center West; 155 Seaport Blvd; Boston; MA; 02110; US Patent Application Number: 20030208078 Date filed: January 28, 2003 Abstract: Generally, the present invention is directed to central nervous system dopamine transporter-imaging agents and methods of use thereof. In certain embodiments, the present invention relates to radiolabeled piperidine derivatives for use as imaging agents in the diagnosis of Parkinson's disease. Another aspect of the present invention relates to piperidine monoamine transporter ligands, comprising a functional group capable of chelating a radionuclide, e.g., technetium, and methods of use thereof. Excerpt(s): This application claims priority to United States Provisional Application for Patent serial No. 60/183,996, filed Feb. 22, 2000. The present invention is directed to central nervous system dopamine transporter-imaging agents, and more particularly, to labeled piperidine derivatives for use as imaging agents in the diagnosis of Parkinson's disease. Each year approximately 50,000 Americans are diagnosed with Parkinson's disease with the estimated total cost to the US economy exceeding $5.6 billion annually. There exists no known test for Parkinson's Disease (PD) and current diagnosis relies on observations of the symptoms relating to deteriorating muscular control. With the difficulties in early diagnosis and no known causes, except for age or head trauma, the need for improved screening and treatment in our aging population continues to grow. While it has been demonstrated that disease progression can be monitored noninvasively in vivo by PET,.sup.1,2 the inaccessibility and cost of PET make such screening ineffective. The availability of a radiolabeled dopamine transporter (DAT) ligand for imaging with single photon emission computed tomography (SPECT) would bring this capability to the majority of the population. Performing such brain imaging studies not only creates the possibility to follow the degeneration rate of the dopaminergic neurons in Parkinson's disease, but also provides an opportunity to estimate therapeutic effects of putative neuro-protective agents in individual patients.sup.3 Hence, an inexpensive and widely available agent for imaging DAT is warranted. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Indole derivatives useful for the treatment of CNS disorders Inventor(s): Andersen, Kim; (Virum, DK), Bang-Andersen, Benny; (Kobenhavn N, DK), Felding, Jakob; (Charlottenlund, DK), Kehler, Jan; (Kgs. Lyngby, DK) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030191133 Date filed: December 9, 2002 Abstract: The present invention relates to dopamine D.sub.4 ligands having the general formula I 1wherein(a) one of Y.sup.1 and Y.sup.2 is N, which is bound to Y.sup.4, and the other of Y.sup.1 and Y.sup.2 is CO, CS, SO, or SO.sub.2 and Y.sup.4 is CH.sub.2;(b) one of Y.sup.1 and Y.sup.2 is N, which is bound to Y.sup.4, and the other of Y.sup.1 and Y.sup.2 is CH.sub.2 and Y.sup.4 is CO, CS, SO or SO.sub.2; or(c) one of Y.sup.1 and Y.sup.2 is N, which is bound to Y.sup.4, and the other of Y.sup.1 and Y.sup.2 is CH.sub.2 and Y.sup.4 is CH.sub.2;Y.sup.3is Z--CH.sub.2, CH.sub.2--Z or CH.sub.2CH.sub.2, and Z is O or S; provided that when Y.sup.1 is N, Y.sup.3 may not be Z--CH.sub.2;W is a bond or an O, S, CO, CS, SO or SO.sub.2 group;n is 0-5, m is 0-5 and m+n is 1-10; provided that when W is O or S, then n.gtoreq.2 and m.gtoreq.1; when W is CO, CS, SO or SO.sub.2, then n.gtoreq.1 and m.gtoreq.1;X is C, CH or N; provided that when X is C, the dotted line indicates a bond, and when X is N or CH, the dotted line is absent;R.sup.1-R.sup.9 are independently selected from hydrogen, halogen, cyano, nitro, amino, hydroxy, C.sub.1-6-alkyl-amino, di-C.sub.1-6-alkyl-amino, C.sub.1-6-alkyl, C.sub.2-6-alkenyl, C.sub.2-6-alkynyl, C.sub.1-6 alkoxy, C.sub.1-6-alkylthio, C.sub.1-6alkyl substituted with hydroxy or thiol, C.sub.3-8-cycloalkyl, C.sub.3-8-cycloalkylC.sub.1-6-alkyl, acyl, thioacyl, aryl, trifluoromethyl, trifluoromethylsulfonyl, and C.sub.1-6 alkylsulfonyl;R.sup.10 is hydrogen, C.sub.1-6-alkyl, C.sub.2-6-alkenyl, C.sub.2-6-alkynyl, C.sub.1-6-alkyl substituted with hydroxy or thiol, C.sub.3-8cycloalkyl, C.sub.3-8-cycloalkyl-C.sub.1-6-alkyl, aryl, aryl-C.sub.1-6-alkyl, acyl, thioacyl, C.sub.1-6-alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl, or a pharmaceutically acceptable acid addition salt thereof.The compounds of the invention are potent dopamine D.sub.4 receptor ligands. Excerpt(s): This application is a continuation of International application no. PCT/DK01/00406, filed Jun. 13, 2001, and claims priority under 35 U.S.C.sctn.119 of U.S. provisional application serial No. 60/212,445, filed Jun. 16, 2000. The prior applications are hereby incorporated by reference, in their entirety. The present invention relates to a novel class of indole derivatives having affinity for the dopamine D.sub.4 receptor. The compounds have antagonistic effect at the dopamine D.sub.4 receptor and are therefore useful in the treatment of certain psychiatric and neurologic disorders, in particular psychoses. Some of the compounds also have affinity for the dopamine D.sub.3 receptor, the 5-HT.sub.2A receptor and/or the 5-HT.sub.2C receptor and some of the compounds are serotonin reuptake inhibitors. wherein A is an indole and Y is a group completing an indane, or a dihydroindole and the other substituents are as defined in the application. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Indole derivatives useful for the treatment of CNS disorders Inventor(s): Bang-Andersen, Benny; (Kobenhavn N, DK), Felding, Jakob; (Charlottenlund, DK), Kehler, Jan; (Kgs. Lyngby, DK) Correspondence: Darby & Darby P.C; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030232822 Date filed: December 17, 2002 Abstract: An indole derivative having the formula 1whereina) Y.sup.1 is N, which is bound to Z, Z and Y.sup.2 are selected from CH.sub.2, CO, CS, SO and SO.sub.2; provided that at least one of Z and Y.sup.2 is CH.sub.2; Y.sup.3is O, S or CHR.sup.7and Y.sup.4is O, S or CHR.sup.8, provided that only one of Y.sup.3 and Y.sup.4 is O or S;b) Y.sup.2 is N, which is bound to Z, Z and Y.sup.1 are selected from CH.sub.2, CO, CS, SO and SO.sub.2; provided that at least one of Z and Y.sup.1 is CH.sub.2; Y.sup.3is CHR.sup.7 and Y.sup.4is O, S or CHR.sup.8;c) Y.sup.2 is N, which is bound to Z, Z and Y.sup.3 are selected from CH.sub.2, CO, CS, SO and SO.sub.2 provided that at least one of Z and Y.sup.3 is CH.sub.2; Y.sup.1 is CHR.sup.6 and Y.sup.4 is O, S or CHR.sup.8;W is a bond, O, S, CO, CS, SO or SO.sub.2;n is 0-5, m is 0-5 and n+m is 1-6; provided that when W is O or S, then n.gtoreq.2 and m.gtoreq.1; when W is CO, CS, SO or SO.sub.2, then n.gtoreq.1 and m.gtoreq.1;X is C, CH or N, provided that when X is C, the dotted line indicates a bond, and when X is N or CH, the dotted line indicates no bond;one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 forms a bond to X and the others of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 and R.sup.9-R.sup.12 are independently selected from hydrogen, halogen, cyano, nitro, amino, hydroxy, C.sub.1-6-alkyl-amino, di-( C.sub.1-6-alkyl )-amino, C.sub.1-6-alkyl, C.sub.2-6-alkenyl, C.sub.2-6-alkynyl, C.sub.1-6 alkoxy, C.sub.1-6-alkylthio, C.sub.1-6-alkyl substituted with hydroxy or thiol, C.sub.3-8cycloalkyl, C.sub.3-8-cycloalkyl-C.sub.1-6-alkyl, acyl, thioacyl, trifluoromethyl, trifluoromethylsulfonyl or C.sub.1-6 alkylsulfonyl;R is hydrogen, C.sub.1-6-alkyl, C.sub.2-6-alkenyl, C.sub.2-6-alkynyl, C.sub.1-6-alkyl substituted with hydroxy or thiol, C.sub.3-8-cycloalkyl, C.sub.3-8-cycloalkyl-C.sub.1-6-alkyl, acyl, thioacyl, trifluoromethylsulfonyl and C.sub.1-6 alkylsulfonyl;or pharmaceutically acceptable salts thereof.The compounds of the invention are potent dopamine D.sub.4 ligands. Excerpt(s): This application is a continuation of International application no. PCT/DK01/00407, filed Jun. 13, 2001. The prior application is hereby incorporated by reference, in its entirety. The present invention relates to a novel class of indole derivatives having affinity for the dopamine D.sub.4 receptor. The compounds are therefore useful in the treatment of certain psychiatric and neurologic disorders, in particular psychoses. The compounds also have affinity for the 5-HT.sub.2A receptor. Dopamine D.sub.4 receptors belong to the dopamine D.sub.2 subfamily of receptors, which is considered to be responsible for the antipsychotic effect of neuroleptics. The side effects of neuroleptic drugs, which primarily exert their effect via antagonism of D.sub.2 receptors, are known to be due to D.sub.2 receptor antagonism in the striatal regions of the brain. However, dopamine D.sub.4 receptors are primarily located in areas of the brain other than striatum, suggesting that antagonists of the dopamine D.sub.4 receptor will be devoid of extrapyramidal side effects. This is illustrated by the antipsychotic clozapine, which exerts higher affinity for D.sub.4 than D.sub.2 receptors and is lacking extrapyramidal side effects (Van Tol et al. Nature 1991, 350, 610; Hadley Medicinal Research Reviews 1996, 16, 507-526 and Sanner Exp. Opin. Ther. Patents 1998, 8, 383-393). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Intradermal delivery of substances Inventor(s): Pinkerton, Thomas C.; (Kalamazoo, MI) Correspondence: Harness, Dickey, & Pierce, P.L.C; 7700 Bonhomme, Ste 400; ST. Louis; MO; 63105; US Patent Application Number: 20040073160 Date filed: June 29, 2001 Abstract: A method for administration of a substance into the dermis of a mammal is disclosed. The method involves administration into the dermis by injection which results in improved systemic absorption relative to that obtained upon subcutaneous administration of the substance. The substance administered may be a growth hormone, a low molecular weight heparin or a dopamine receptor agonist. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/606,909 filed Jun. 29, 2000. The present invention relates to methods and devices for administration of substances into the intradermal layer of skin. The importance of efficiently and safely administering pharmaceutical substances such as diagnostic agents and drugs has long been recognized. Although an important consideration for all pharmaceutical substances, obtaining adequate bioavailability of large molecules such as proteins that have arisen out of the biotechnology industry has recently highlighted this need to obtain efficient and reproducible absorption (Cleland et al., Curr. Opin. Biotechnol. 12: 212-219, 2001). The use of conventional needles has long provided one approach for delivering pharmaceutical substances to humans and animals by administration through the skin. Considerable effort has been made to achieve reproducible and efficacious delivery through the skin while improving the ease of injection and reducing patient apprehension and/or pain associated with conventional needles. Furthermore, certain delivery systems eliminate needles entirely, and rely upon chemical mediators or external driving forces such as iontophoretic currents or electroporation or thermal poration or sonophoresis to breach the stratum corneum, the outermost layer of the skin, and deliver substances through the surface of the skin. However, such delivery systems do not reproducibly breach the skin barriers or deliver the pharmaceutical substance to a given depth below the surface of the skin and consequently, clinical results can be variable. Thus, mechanical breach of the stratum comeum such as with needles, is believed to provide the most reproducible method of administration of substances through the surface of the skin, and to provide control and reliability in placement of administered substances. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for treating obesity Inventor(s): Gadde, Kishore M.; (Durham, NC), Krishnan, K. Ranga R.; (Durham, NC) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20040033965 Date filed: May 19, 2003 Abstract: The present invention relates, in general, to obesity, and, in particular, to a method of treating obesity and minimizing metabolic risk factors associated therewith using, for example, zonisamide or other weight-loss promoting anticonvulsant either
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alone or in combination with bupropion or other compound that enhances the activity of norepinephrine and/or dopamine via uptake inhibition or other mechanism. Excerpt(s): This application claims priority from Prov. Appln. No. 60/380,874, filed May 17, 2002, the content of which is incorporated herein by reference. The prevalence of obesity has risen significantly in the past decade in the United States and many other developed countries, (Fiegal et al, Int. J. Obesity 22:39-47 (1998), Mokdad et al, JAMA 282:1519-1522 (1999)). Because obesity is associated with a significantly elevated risk for type 2 diabetes, coronary heart disease, hypertension, and numerous other major illnesses, and overall mortality from all causes (Must et al, JAMA 282:1523-1529 (1999), Calle et al, N. Engl. J. Med. 341:1097-1105 (1999)), weight reduction is critical for the obese patient (Blackburn, Am. J. Clin. Nujtr. 69:347-349 (1999), Galuska et al, JAMA 282:1576 (1999)). There is good evidence that pharmacotherapy can enhance weight loss when combined with interventions aimed at changing life style (National Heart, Lung and Blood Institute, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report, NIH Publication No. 98-4083, September 1998). Yet, the available pharmacological therapies to facilitate weight loss fail to provide adequate benefit to many obese patients because of side effects, contraindications or lack of positive response (National Heart, Lung and Blood Institute, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report, NIH Publication No. 98-4083, September 1998). Hence, there is impetus for developing new and alternative treatments for management of obesity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of screening ptp.cedilla. activitiy promoter or inhibitor Inventor(s): Fujikawa, Akihiro; (Aichi, JP), Noda, Masaharu; (Aichi, JP) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030186284 Date filed: January 24, 2003 Abstract: An object of the present invention is to provide a remedy for dysfunction of central monoamine pathway, a method for screening a PTP.zeta. inhibitor or activator, which is useful as a remedy for gastric ulcer caused by Helicobacter pylori or pleiotrophin which is a heparin-binding secretory protein, and a non-human model animal being hyposensitive to a stimulant drug, VacA which is a toxin of Helicobacter pylori, or pleiotrophin by utilizing the physiological function of PTP.zeta. After administering a subject material to PTP.zeta. knockout mice and wild-type mice, PTP.zeta. activity in the PTP.zeta. knockout mice and the wild-type mice is compared and evaluated to screen a PTP.zeta. inhibitor or activator. Examples of the comparison and the evaluation of the PTP.zeta. activity include the comparison and the evaluation of the function of central monoamine pathway such as changes in the level of central monoamine metabolism, sensitivity to a stimulant drug, the presence of dysfunction of mesolimbic dopamine pathway, level of acclimation to new circumstances, or stressresponsiveness, and the comparison and the evaluation of the level of binding to VacA, a toxin of Helicobacter pylori, or pleiotrophin. Excerpt(s): The present invention relates to a remedy for dysfunction of central monoamine pathway with the use of a non-human animal such as a mouse or the like
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which is generated by a homologous recombination technique for genes and is deficient in its receptor-type protein tyrosine phosphatase (PTP.zeta./RPTP.beta.) gene, a screening of a remedy for gastric ulcer caused by Helicobacter pylori or the like, a nonhuman model animal being hyposensitive to a central stimulant drug (an addictive drug) and a non-human model animal being hyposensitive to VacA, a toxin of Helicobacter pylori, or the like. When a cell receives a stimulus from outside, its intracellular signaling pathway is activated to induce proliferation, differentiation, apoptosis and the like of the cell. Tyrosine phosphorylation of intracellular proteins acts an extremely important role in various phases of the signaling pathway, and the state of tyrosine phosphorylation of each protein is always regulated by dynamic equilibrium of delicate balance of two families of enzymes, tyrosine kinase (PTK) and tyrosine phosphatase (PTP). It is known that this tyrosine phosphorylation of proteins is involved in controlling the efficiency of neural circuit formation and neurotransmission in brains (SEITAI NO KAGAKU Vol. 48, No. 6, 534-538, (1997); PROTEIN, NUCLEIC ACID AND ENZYME Vol. 43, No. 8, 1136-1143 (1998)), and is important for the formation and the maintenance of the functions in an immune system and other organs (PROTEIN, NUCLEIC ACID AND ENZYME Vol. 43, No. 8, 1131-1135 (1998)). On the other hand, it is reported that the abnormal tyrosine phosphorylation of proteins is involved in defects in neural circuit formation, disturbance of memory and learning, abnormal apoptosis, tumorigenesis or the like (PROTEIN, NUCLEIC ACID AND ENZYME Vol. 43, No. 8, 1186-1192 (1998)). To date, more than 80 kinds of PTP have been identified, and it is presumed that the number of genes of PTP in human would reach to 500. Similar to PTK, PTP is classified into two types: a receptor type and a nonreceptor type. A receptor-type PTP has two or one enzymic domain intracellularly, and is classified into several groups according to the characteristics of its extracellular domain. PTP.zeta., which has a carbonic anhydrase domain in N-terminal, has been identified as a receptor-type tyrosine phosphatase specific to the central nervous system. The inventors of the present invention have reported that PTP.zeta. is a receptor of growth factors including pleiotrophin and midkine (J. Biol. Chem. 271, 21446-21452, 1996; J. Cell Biol. 142, 203-216, 1998; J. Biol. Chem. 274, 12471-12479, 1999). In addition, PTP.zeta. is known to interact with cell adhesion molecules which belong to the immunogloblin super family, such as N-CAM, and is thought to be responsible for important functions in differentiation, migration and neurotransmission of neurons. The present inventors have already generated a PTP.zeta. gene-deficient mouse and reported that PTP.zeta. has expressed in both neurons and astrocytes (Neuroscience Letters 274, 135-138, 1998). The PTP.zeta. gene-deficient mouse has grown and propagated normally, and no major morphologic abnormality has been identified. However, the physiological role of PTP.zeta. has been hardly elucidated so far. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for identifying compounds for regulating muscle mass or function using dopamine receptors Inventor(s): Isfort, Robert Joseph; (Fairfield, OH), Sheldon, Russell James; (Fairfield, OH) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20030170741 Date filed: November 18, 2002
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Abstract: Screening methods for identifying compounds that bind to or activate (D.sub.1 or D.sub.5 dopamine receptors individually or in combination) or regulate or potentially regulate skeletal muscle mass or function in vivo. Also disclosed are screening methods for identifying compounds that prolong or augment the activation of D.sub.1 or D.sub.5 dopamine receptors or of D.sub.1 or D.sub.5 dopamine receptor signal transduction pathways and increase D.sub.1 or D.sub.5 dopamine receptor expression. Pharmaceutical compositions comprising D.sub.1 or D.sub.5 dopamine receptor agonists, antibodies to D.sub.1 or D.sub.5 dopamine receptors and methods for increasing skeletal muscle mass or function or for the treatment of skeletal muscle atrophy using D.sub.1 or D.sub.5 dopamine receptors as the target for intervention and methods for treatment of muscular dystrophies are described. Excerpt(s): This application claims priority from U.S. Provisional Applications Serial No. 60/349,620 filed on Jul. 1, 2002, which is herein incorporated by reference in its entirety. The present invention relates to methods of identifying candidate compounds for regulating skeletal muscle mass or function or regulating the activity or expression of a dopamine receptor (dopamine receptor). The invention also relates to methods for the treatment of skeletal muscle atrophy or methods for inducing skeletal muscle hypertrophy using D.sub.1 or D.sub.5 dopamine receptors as the target for intervention and to methods of treating muscular dystrophies using D.sub.1 or D.sub.5 dopamine receptors as targets. Dopamine has multiple physiological effects including central and peripheral activities. In the brain, dopamine controls a multitude of functions including locomotor activity, cognition, emotion, positive reinforcement, food intake and endocrine regulation. In the periphery, dopamine functions as a modulator of cardiovascular activity (both cardiac and vascular function), catecholamine release, hormone secretion, renal function and gastrointestinal motility (reviewed in Missale et al., 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treating or preventing erectile dysfunction Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20030195261 Date filed: March 25, 2003 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions including, but are not limited to, erectile dysfunction, affective disorders, weight gain, cerebral functional disorders, pain, obsessive-compulsive disorder, substance abuse, chronic disorders, anxiety, eating disorders, migraines, and incontinence. The methods comprise the administration of a dopamine reuptake inhibitor and optionally an additional pharmacologically active compound. Pharmaceutical compositions and dosage forms are also disclosed that comprise a dopamine reuptake inhibitor and optionally an additional pharmacologically active compound. Preferred dopamine reuptake inhibitors are racemic or optically pure sibutrarnine metabolites and pharmaceutically acceptable salts, solvates, and clathrates thereof. Preferred additional pharmacologically active compounds include drugs that affect the central nervous system, such as 5-HT.sub.3 antagonists.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/097,665, filed Aug. 24, 1998, and U.S. Provisional Application No. 60/099,306, filed Sep. 2, 1998, both of which are incorporated herein in their entireties by reference. The invention relates to methods of using, and compositions comprising, dopamine reuptake inhibitors and, in particular, racemic and optically pure metabolites of sibutramine. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]-3- methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Modular approach to on-line synthesis, drug transformations using immobilized enzyme reactors
discovery
and
biochemical
Inventor(s): Markoglou, Nektaria; (Montreal, CA), Wainer, Irving; (Washington, DC) Correspondence: Thomas M Boyce; Fulbright & Jaworski; Suite2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20040053355 Date filed: September 29, 2003 Abstract: A coupled system using extremely different enzymes with incompatible cofactors and reaction conditions has been constructed using standard liquid chromatographic formats and open tubular formats. One of the significant aspects of the present invention lies in the development of the liquid chromatographic on-line enzyme cascade. This has been illustrated by the biosynthetic pathway involving dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase which encompass the synthesis of the key neurotransmitters, norepinephrine and epinephrine. The results demonstrate for the first time the immobilization of dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase. The IMERs are active and can be used in a liquid chromatographic format for qualitative and quantitative determinations. The IMER-HPLC system can be used to carry out standard Michaelis-Menten enzyme kinetic studies and to quantitatively determine enzyme kinetic constants, identify specific enzyme inhibitors, provide information regarding the mode of inhibition and the inhibitor constants (K.sub.i). A second significant aspect of the present invention lies in the ability of the immobilized enzyme reactors to be used independently or as a combination, thus providing a unique opportunity to explore the interrelationships between these enzymes, to investigate the source of diseases and to design new drug entities for identified clinical syndromes. Excerpt(s): The present invention relates to immobilized enzyme reactors (IMERs). More specifically, the present invention is concerned with the application of a liquid chromatographic system based upon coupled on-line immobilized enzyme reactors (HPLC-IMERs) in organic synthesis, biochemistry and pharmacology. The novel coupled enzyme system of the present invention allows for on-line chromatographic purification and structural identification of products. In an alternative embodiment, open tubular columns coupled to a mass spectrometer or other detection device may be used. Additionally, the coupled enzyme system of the present invention may be used in basic research into synthetic and metabolic pathways as well as in the discovery of new pharmaceutical substances. The therapeutic and toxic effects of drugs are governed by
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the interactions of these molecules with biopolymers such as proteins, receptors and enzymes (Katzung, 1995). The biopolymer-drug interactions define a drug's pharmacological fate. As such, there have been interdisciplinary efforts amongst fields such as medicine, pharmacology and biochemistry to develop methods for the identification and characterization of these interactions. In recent years there have been significant developments in the study of the basis of enzyme-drug interactions. The understanding of how enzymes react with drugs and bring about chemical changes in vivo is a key factor for the determination of drug pharmacodynamics and pharmacokinetics, and is also important in the development of new therapeutic agents. The conventional uses of enzymes within many fields have been based upon enzymes in their soluble forms (Dixon et al., 1979). In vivo most enzymes are naturally found within a cellular matrix and can be membrane bound. Consequently, many previously reported in vitro assays that utilize solubilized enzymes are not a true reflection of what is occurring in vivo. This has naturally led to the development of immobilized enzymes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Monoamine oxidase (MAO) inhibitors and uses thereof Inventor(s): Burton, Harold R.; (Lexington, KY), DeLorenzo, Robert J.; (Richmond, VA), Williams, Jonnie R.; (Manakin-Sabot, VA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030185908 Date filed: March 26, 2003 Abstract: The present invention provides a group of tobacco alkaloids, tobacco extract, Yerbamat extract, and an extract of chewing gum and lozenges which are modulators of monoamine oxidase (MAO) activity (i.e., compounds and substances which inhibit MAO enzyme and prevent its biological activity). The MAO inhibitors of the present invention can cause an increase in the level of norepinephrine, dopamine, and serotonin in the brain and other tissues, and thus can cause a wide variety of pharmacological effects mediated by their effects on these compounds. The MAO inhibitors of the present invention are useful for a variety of therapeutic applications, such as the treatment of depression, disorders of attention and focus, mood and emotional disorders, Parkinson's disease, extrapyramidal disorders, hypertension, substance abuse, smoking substitution, anti-depression therapy, eating disorders, withdrawal syndromes, and the cessation of smoking. Excerpt(s): This application is a division of application Ser. No. 10/042,164, filed Jan. 11, 2002, which is a division of Ser. No. 09/325,852, filed Jun. 4, 1999, which claims priority under 35 U.S.C.sctn.119(e) to Provisional Application No. 60/088,117, filed Jun. 5, 1998. The present invention relates to the novel use of compounds and substances which are capable of modulating monoamine oxidase (MAO) activity by inhibiting the MAO enzyme. The present invention also relates to MAO inhibitors and their therapeutic use as a drug or dietary supplement in the treatment of various conditions or disorders, including psychiatric and neurological illnesses. More particularly, the present invention relates to the therapeutic use of tobacco alkaloids, Yerbamat (Ilex paraguariensis) extract, or tobacco extracts to inhibit MAO activity to provide a treatment for various disorders or conditions. By inhibiting MAO activity, MAO inhibitors can regulate the level of monoamines and their neurotransmitter release in different brain regions and in the body (including dopamine, norepinephrine, and
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serotonin). Thus, MAO inhibitors can affect the modulation of neuroendocrine function, respiration, mood, motor control and function, focus and attention, concentration, memory and cognition, and the mechanisms of substance abuse. Inhibitors of MAO have been demonstrated to have effects on attention, cognition, appetite, substance abuse, memory, cardiovascular function, extrapyramidal function, pain and gastrointestinal motility and function. The distribution of MAO in the brain is widespread and includes the basal ganglia, cerebral cortex, limbic system, and mid and hind-brain nuclei. In the peripheral tissue, the distribution includes muscle, the gastrointestinal tract, the cardiovascular system, autonomic ganglia, the liver, and the endocrinic system. The present invention overcomes the problems and limitations of the prior art by providing methods and systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Monoamine reuptake inhibitors for treatment of CNS disorders Inventor(s): Elliott, Mark L.; (Canterbury, CT), Howard, Harry R. JR.; (Bristol, CT), Schmidt, Christopher J.; (Old Lyme, CT), Seeger, Thomas F.; (Mystic, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20040048856 Date filed: September 4, 2003 Abstract: The present invention relates to compounds that are useful exhibit activity as serotonin, norepinephrine and dopamine reuptake inhibitors, and their pharmaceutically acceptable salts, and their use in the treatment of central nervous system and other disorders. Excerpt(s): Serotonin Selective Reuptake Inhibitors (SSRIs) currently provide efficacy in the treatment of major depressive disorder (MDD) and are generally perceived by psychiatrists and primary care physicians as effective, well-tolerated and easily administered. However, they are associated with undesirable features, such as high incidence of sexual dysfunction, delayed onset of action and a level on nonresponsiveness estimated to be as high as 30% (see M. J. Gitlin, Journal of Clinical Psychiatry, 1994, 55, 406-413 and R. T. Segraves, Journal of Clinical Psychiatry, 1992, 10(2), 4-10). Preclinical and clinical evidence has indicated that the sexual dysfunction associated with SSRI therapy can be reduced through the use of dopamine reuptake inhibitors (DRIs), such as bupropion (see A. K. Ashton, Journal of Clinical Psychiatry, 1998, 59(3), 112-115). Furthermore, the combination of SRI and DRI may hasten the onset of action as well as offering relief to refractory patients, possibly through a synergistic mechanism (see R. D. Marshall et al, Journal of Psychopharmacology, 1995, 9(3), 284286). This invention relates to novel biaryl ether derivatives that exhibit activity as monoamine (e.g., dopamine, serotonin) reuptake inhibitors, to pharmaceutical compositions containing such compounds and to methods of using such compounds to treat central nervous system (CNS) and other disorders. U.S. Pat. No. 4,018,830, published on Apr. 19, 1997, refers to phenylthioaralkylamines and 2phenylthiobenzylamines which are active as antiarrhythmics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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N-and o-substituted 4-[2-( diphenylmethoxy) -ethyl]-1- (phenyl) methyl) piperidine analogs and methods of treating cns disorders therewith Inventor(s): Dutta, Aloke A; (Novi, MI) Correspondence: Brooks & Kushman P.C.; 1000 Town Center; Twenty-second Floor; Southfield; MI; 48075; US Patent Application Number: 20030225133 Date filed: March 28, 2003 Abstract: Nand O-substituted 4[2-diaromaticmethoxy and methylamino)alkyl]piperidin- es exhibit high CNS activity with respect to the dopamine transporter (DAT) and serotonin transporter (SERT). Preferred compounds exhibit highly differential behavior as between the DAT and SERT and between the DAT and the norepinephrine transporter (NET). The compounds have utility in treating CNS disorders, including but not limited to cocaine addiction, depression, and Parkinson's disease. 12 Excerpt(s): The present invention pertains to novel pharmacologically active compounds which exhibit activity for monoamine transporter systems, specifically for the dopamine transporter ("DAT"), serotonin transporter ("SERT"), and norepinephrine transporter ("NET"). The novel compounds exhibit a high differential in activity for the DAT relative to the SERT. The dopamine transporter is a presynaptically located macromolecule which plays an important role in pathophysiocological processes in the central nervous system (CNS). The DAT terminates dopaminergic neurotransmission by reaccumulation of released dopamine into presynaptic neurons, M. J. Kuhar, "Neurotransmitter Uptake: A Tool in Identifying Neurotransmitter Specific Pathways", LIFE SCI., 13, 1623-34, 1973. In cocaine addiction, binding of cocaine to the DAT and consequent blockage of dopamine uptake appears to be related to the reinforcing properties of the drug. M. E. A. Reith et al., "Structural Requirements for Cocaine Congeners to Interact With Dopamine and Serotonin Uptake Sites in Mouse Brain and to Induced Stereotyped Behavior", BIOCHEM. PHARMACOL., 1986, 35, 1123-1129; M. C. Ritz et al., "Cocaine Inhibition of Ligand Binding At Dopamine, Norpinephrine and Serotonin Transporters: A Structure-Activity Study", LIFE. SCI., 1990, 46, 635-645; M. C. Ritz et al., "Cocaine Receptors On Dopamine Transporters Are Related to Self-Administration of Cocaine", SCIENCE, 1987, 237, 1219-1223; B. Giros et al., "Hyperlocomotion and Indifference to Cocaine and Amphetamine in Mice Lacking the Dopamine Transporter", NATURE, 1996, 379, 606-612. Also associated with the transport function is concentration of neurotoxic chemicals in dopaminergic neurons which is implicated in Parkinson's disease. The transporter macromolecule may be a marker for Parkinson's, H. Shoemaker et al., NAUNYN SCHMIEDEBERGS ARCH. PHARMACOL., 1985, 329, 227-235 and J.M. Maloteaux et al., EUR. J. PHARM., 1988, 156, 331-340, as evidenced by its absence in tissue sections of Parkinson's diseased putamen. H. B. Niznik et al., ARCH. BIOCHEM. BIOPHYS., 1990, 276, 424-432 and M. J. Kaufman et al., SYNAPSE, 1991, 9, 43-49. Consequently, potent yet selective ligands for the DAT have potential for in vivo monitoring of primary targets of cocaine in the brain, for characterization of cocaine binding sites, for pharmacotherapeutic agents for treatment of cocaine addition, and for monitoring of Parkinson's Disease. Cocaine is known to bind to various neurotransporter systems in the brain, M. E. A. Reith et al., op. cit., but the reinforcing effect of cocaine which is a factor in cocaine addition, is believed to be initiated by binding to the DAT, causing inhibition of dopamine transport. Phencyclidine (PCP), a psychoactive drug of abuse, is also known to exhibit at least some of its behavioral effects through binding to the DAT. K. M. Johnson, "Phencyclidine: Behavioral and
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Biochemical Evidence Supporting a Role For Dopamine", FED. PROC., 1983, 42, 25792583; E. D. French et al., "Phencyclidine Binding Sites in the Nucleus Accumbens and Phencyclidine-Induced Hyperactivity are Decreased Following Lesions of the Mesolimbic Dopamine System", EUR. J. PHARMACOL., 1985, 116, 1-9. The DAT further plays a crucial role in the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) which induces idiopathic Parkinson's syndrome in humans. J. Langston et al., MPTP: Current Concepts and Controversies", CLIN. NEUROPHARMAC., 1986, 9, 485-507; H. Kinemuchi et al., "The Neurotoxicity of 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its Relevance to Parkinson's Disease", NEUROCHEM. INT., 1987, 11, 359-373. The serotonin transporter (SERT) is also implicated in numerous neurological processes. For example, SERT is strongly implicated in depression and drug addiction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
N-aryl diazaspiracyclic compounds and methods of preparation and use thereof Inventor(s): Bhatti, Balwinder S.; (Winston-Salem, NC), Miller, Craig Harrison; (Winston-Salem, NC), Schmitt, Jeffrey Daniel; (Winston-Salem, NH) Correspondence: Womble Carlyle Sandridge & Rice, Pllc; P.O. Box 7037; Atlanta; GA; 30357-0037; US Patent Application Number: 20040067930 Date filed: June 27, 2003 Abstract: Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteroaryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle). Excerpt(s): This document claims priority to and the benefit of the filing date of copending provisional application entitled "N-Aryl Diazaspiracyclic Compounds and Methods of Preparation and Use Thereof" assigned serial No. 60/394,337, and filed Jul. 5, 2002, which is hereby incorporated by reference. The present invention relates to pharmaceutical compositions incorporating compounds capable of affecting nicotinic cholinergic receptors, for example, as modulators of specific nicotinic receptor subtypes. The present invention also relates to methods for treating a wide variety of conditions and disorders, particularly those associated with dysfunction of the central and autonomic nervous systems. Nicotine exhibits a variety of pharmacological effects (Pullan et al., N. Engl. J. Med. 330:811-815 (1994)), some of which are due to neurotransmitter release (See, for example, Sjak-shie et al., Brain Res. 624:295 (1993),
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where neuroprotective effects of nicotine are proposed). For example, acetylcholine, dopamine, norepinephrine, serotonin and glutamate are released by neurons upon administration of nicotine (Rowell et al., J. Neurochem. 43:1593 (1984); Rapier et al., J. Neurochem. 50:1123 (1988); Sandor et al., Brain Res. 567:313 (1991) and Vizi, Br. J. Pharmacol. 47:765 (1973), (Hall et al., Biochem. Pharmacol. 21:1829 (1972), (Hery et al., Arch. Int. Pharmacodyn. Ther. 296:91 (1977)), and Toth et al., Neurochem Res. 17:265 (1992)). Confirmatory reports and additional recent studies show that nicotine administration modulates glutamate, nitric oxide, GABA, takykinins, cytokines and peptides in the central nervous system (CNS) (reviewed in Brioni et al., Adv. Pharmacol. 37:153 (1997)). Nicotine also reportedly potentiates the pharmacological behavior of certain pharmaceutical compositions used to treat certain disorders. See, for example, Sanberg et al., Pharmacol. Biochem. & Behavior 46:303 (1993); Harsing et al., J. Neurochem. 59:48 (1993) and Hughes, Proceedings from Intl. Symp. Nic. S40 (1994). Various additional beneficial pharmacological effects of nicotine have been proposed. See, for example, Decina et al., Biol. Psychiatry 28:502 (1990); Wagner et al., Pharmacopsychiatry 21:301 (1988); Pomerleau et al., Addictive Behaviors 9:265 (1984); Onaivi et al., Life Sci. 54(3):193 (1994); Tripathi et al., J. Pharmacol. Exp. Ther. 221:91(1982) and Hamon, Trends in Pharmacol. Res.15:36 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nasal delivery of apomorphine in combination with glycol derivatives Inventor(s): Achari, Raja G.; (Millington, NJ), Ahmed, Shamin; (Central Islip, NY), Behl, Charanjit R.; (Hauppauge, NY), Demeireles, Jorge C.; (Syosset, NY), Liu, Tianquing; (Central Islip, NY), Romeo, Vincent D.; (Massapequa Park, NY), Sileno, Anthony P.; (Brookhaven Hamlet, NY) Correspondence: Joshua King; Graybeal Jackson Haley Llp; Suite 350; 155 - 108th Avenue NE; Bellevue; WA; 98004-5901; US Patent Application Number: 20040101484 Date filed: November 5, 2003 Abstract: Intranasal delivery compositions and methods for the delivery of dopamine receptor agonists are provided which are effective for the treatment14 of sexual dysfunction in a mammal without causing substantial intolerable adverse side effects to the mammal, in particular adverse nasal effects. Nasally administered compositions for treating sexual dysfunction in a mammal are also provided which include a therapeutically effective amount of a dopamine receptor agonist which has been dispersed in a system to improve its solubility and/or stability. Excerpt(s): The present invention relates generally to intranasal delivery methods and dosage forms of apomorphine. More particularly, methods and dosage forms for the safe and reliable intranasal delivery of apomorphine with minimal adverse nasal effects to treat sexual dysfunction, including erectile dysfunction, in a mammal are provided. Apomorphine is a potent dopamine receptor agonist which has a variety of uses. For example, it has been effectively used as an adjunctive medication in the treatment of Parkinson's disease which is complicated by motor fluctuations (T. van Laar et al., Arch. Neurol., 49: 482-484 (1992)). In particular, apomorphine has been used for relieving "offperiod" symptoms in Parkinson patients with such response fluctuations. In the study by van Laar et al., the intranasally applied apomorphine used to achieve the results reportedly included an aqueous solution of apomorphine hydrochloride (HCL) at a concentration of 10 mg/ml. This formulation is also used for parenteral application and
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is published in different Pharmacopeia's. Also, U.S. Pat. No. 5,756,483 issued to Merkus (hereinafter "the '483 patent") which is hereby incorporated by reference, discloses the intranasal delivery of a variety of compositions, including apomorphine in combination with a cyclodextrin and/or a polysaccharide and/or a sugar alcohol for treating Parkinson's disease. The '483 patent, however, discloses very narrow dosage ranges of 0.1 to 2 mg of apomorphine per nostril which is specifically tailored for the treatment of the "off-period" symptoms of Parkinson's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel heterocyclic urea derivatives and their use as dopamine D3 receptor ligands Inventor(s): Bordeau, Kenneth J.; (Kintnersville, PA), Brooks, Sarah; (Belmont, CA), Hemmerle, Horst; (Indianapolis, IN), Hendrix, James A.; (Hillsborough, NJ), Mueller, Paul J.; (Hoboken, NJ), Strupczewski, Joseph T.; (Flemington, NJ), Urmann, Matthias; (Eschborn, DE), Zhao, Xu-Yang; (Bridgewater, NJ) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206, Mail Code: D-303a; Bridgewater; PA; 08807; US Patent Application Number: 20030229066 Date filed: February 19, 2002 Abstract: The invention relates to heterocyclic substituted urea derivatives that display selective binding to dopamine D.sub.3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D.sub.3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, NeurolepticInduced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D.sub.3 receptors. Excerpt(s): 1) Psychoses (including schizophrenia)--See, for example, Biochem Pharmacol, 1992, 3(4), 659-66; Clin Neuropharmacol, 1993,16(4), 295-314; Neuropsychopharmacology, 1997, 16(6), 375-84; Am J Psychiatry, 1999,156(4), 610-616; Psychopharmacology (Berl), 1995, 120(1), 67-74. 2) Substance dependence and substance abuse--See, for example, Neuroreport, 1997, 8(9-10), 2373-2377; J Pharmacol Exp Ther, 1996, 278(3),1128-37; Brain Res Mol Brain Res, 1997, 45(2), 335-9. 3) Mood Disorders (including mania, depressive disorders and bipolar disorders)--See, for example, Clin Neuropharmacol, 1998, 21 (3),176-80; Am J Med Genet, 1998, 81 (2),192-4; J Clin Psychiatry, 1995, 56(11), 514-518; J Clin Psychiatry, 1995, 56(9), 423-429; Am J Med Genet,1995, 60(3), 234-237; Pharmacopsychiatry, 1999, 32(4), 127-135; J Affect Disord, 1999, 52(1-3), 275-290; Am J Psychiatry, 1999,156(4), 610-616. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel pharmaceutical compositions administering n-0923 Inventor(s): Grapatin, Sabine; (Langenfeld, DE), Krein, Cliff; (Overath, DE), Rimpler, Stephan; (Hilden, DE), Thelen, Markus; (Monheim, DE) Correspondence: Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030166709 Date filed: February 11, 2003 Abstract: The invention relates to a pharmaceutical composition for administering the dopamine agonist N-0923 in depot form. The invention makes available for the first time a depot form of N-0923, which achieves a therapeutically significant plasma level over a period of at least 24 hours after administration to a patient. As a result of poor oral bio-availability and the short plasma half-life, N-0923 was previously administered either by an intravenous drip or by transdermal systems. Preferred embodiments of said invention are oily suspensions, containing the active ingredient N-0923 in a solid phase, in addition to anhydrous pharmaceutical preparations of N-0923. Excerpt(s): This invention relates to a pharmaceutical composition for administering the dopamine agonist N-0923 (Rotigotine) in depot form. Preferred implementations are in the form of oily suspensions containing the active agent N-0923 in its solid phase, as well as anhydrous pharmaceutical preparations of N-0923. The invention further relates to the use of solid N-0923 for producing thermally sterilizable medications. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel uses of combined selective dopamine d2 receptor antagonists and 5-ht receptor agonists Inventor(s): Bartoszyk, Gerd; (Weiterstadt, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040014788 Date filed: May 13, 2003 Abstract: Use of compounds being combined selective dopamine D2 receptor antagonists and 5-HT.sub.1A receptor agonists, in particular (R)-(-)-2-[5-4 fluorophenyl)3-pyridylmethyl-aminomethyl]-chromane or a physiologically acceptable salt thereof or N-(4'-fluoro-3-biphenylmethyl)-N-2-(3-cycanophenoxy-ethyl)-amine or a physiologically acceptable salt thereof, for the manufacture of a medicament for use in veterinary medicine for the treatment of self directed traumatic disorders associated with behavioral stressors, compulsive disorders associated with behavioral stressors and/or anxiety disorders associated with behavioral stressors. Excerpt(s): Particularly, the present invention relates to the use of combined selective dopamine D2 receptor antagonists and 5-HT.sub.1A receptor agonists chosen from the group consisting of (R)-(-)-2-[5-(4-fluorophenyl- )-3-pyridylmethylaminomethyl]chromane or physiologically acceptable salts thereof or N-(4'-fluoro-3-biphenylmethyl)N-2-(3-cyano-phenoxy-ethyl)-ami- ne or a physiologically acceptable salt thereof, for the manufacture of a medicament for use in veterinary medicine for the treatment of self directed traumatic disorders associated with behavioral stressors and/or compulsive disorders associated with behavioral stressors and/or anxiety disorders associated with behavioral stressors. (R)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-
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chromane, physiologically acceptable salts thereof (U.S. Pat. No. 5,767,132, column 9, lines 6 to 32) and a process (U.S. Pat. No. 5,767,132, Example 19) by which it/they can be prepared are known from U.S. Pat. No. 5,767,132. The compound which is referred to herein is described in the patent as a combined selective dopamine D2 receptor antagonist and 5-HT.sub.1A receptor agonist. N-(4'-fluoro-3-biphenylmethyl)-N-2-(3cyano-phenoxy-eth- yl)-amine, physiologically acceptable salts thereof (U.S. Pat. No. 5,767,132, column 9, lines 6 to 32) and a process (U.S. Pat. No. 5,767,132, Example 6) by which it/they can be prepared are known from U.S. Pat. No. 5,767,132. The compound which is referred to herein is described in the patent as a combined selective dopamine D2 receptor antagonist and 5-HT.sub.1A receptor agonist. Therefore, the use of (R)-(-)-2[5-(4-fluorophenyl)-3-pyridylmethyl- aminomethyl]-chromane and its physiologically acceptable acid addition salts and the use of N-(4'-fluoro-3-biphenylmethyl)-N-2-(3cyano-phenoxy-- ethyl)-amine and its physiologically acceptable salts thereof for the manufacture of a medicament for prophylaxis and control of the sequelae of cerebral infarction (apoplexia cerebri) such as stroke and cerebral ischaemia, for prophylaxis and control of cerebral disorders, e.g. migraine, especially in geriatrics in a manner similar to certain ergot alkaloids, the treatment of anxiety, tension and depression states, sexual dysfunctions caused by the central nervours system, for disturbances in sleep or absorption of food or for the treatment of psychosis (schizophrenia) is disclosed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical composition for treating fecal incontinence and anal itch Inventor(s): Kamm, Michael A.; (London, GB), Phillips, Robin K.S.; (Northwood, GB) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030216420 Date filed: March 18, 2003 Abstract: Fecal incontinence and anal itch can be treated by administration, more particularly by local application to the anus, of an a adrenergic blocker, nitric oxide synthase inhibitor, prostaglandin F.sub.2.alpha., dopamine, morphine,.beta.-blockers, and 5-Hydroxytryptamine. The patients who benefit most from the invention are those who have a normal or low maximum anal resting pressure and a structurally intact internal anal sphincter muscle, and patients who have had major bowel resection and reanastomisis. Excerpt(s): This invention relates to the treatment of relief of fecal incontinence and anal itch (pruritis ani), particularly for patients who have had a major bowel resection and reanastomosis. Anal or fecal incontinence is the inability to voluntarily control the passage of feces or gas through the anus. It may occur either as fecal soiling or as rare episodes of incontinence for gas or watery stools. It is a very distressing condition that can result in self-inflicted social isolation and despair. Conventional treatments for fecal incontinence include drug therapy to improve stool consistency, such as morphine, loperamide and codeine phosphate to reduce gut motility, and laxatives to soften stools and relieve constipation. Biofeedback training is another treatment which involves muscle strengthening exercises to improve anal canal resting pressure, and squeeze pressure, and to teach symmetry of anal canal function. The most common form of treatment however, is surgical repair, such as the creation of a neo-sphincter which involves grafting on muscle from other parts of the anus, or a colostomy. (Gastroenterology in Practice, Summer 1995, p18-21; Dig Dis 1990; 8:179-188; and The
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New England Journal of Medicine, April 1992, p1002-1004). In mild cases of anal leakage, the patient will often try and plug the anus with a ball of cotton wall. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical compositions containing alpha3beta4 nicotinic receptor antagonists and methods of their use Inventor(s): Simon, David Lew; (Mansfield, CT) Correspondence: David L. Simon, M.D.; P.O. Box 618; Mansfield; CT; 06250; US Patent Application Number: 20030199496 Date filed: July 1, 2002 Abstract: A pharmaceutical composition comprising an.alpha.3.beta.4 nicotinic receptor antagonist effective to diminish the brain-derived feeling of pleasure due to increased dopamine in the pleasure-reward center of the brain typically associated with administration of an opioid agonist analgesic, a muscle relaxant, an anti-seizure medication, an anxiolytic drug, an amphetamine, a central nervous system stimulant, a tetrahydrocannabinol or that associated with an otherwise pleasurable or selfreinforcing behavior. Excerpt(s): This invention relates to pharmaceutical compositions, specifically to those containing opioid agonist analgesics as at least one component of the composition, and also to pharmaceutical compositions containing a blocker of a recently discovered central nervous system receptor--the.alpha.3.beta.4 receptor--as at least one component of the composition, and the various methods of use of such pharmaceutical compositions. Opioid agonist analgesics have long been a cornerstone of pharmaceutical management of pain and other medical maladies such as loose stool or diarrhea. However, use of opioid agonist analgesics may be accompanied by feeling euphoria as a reaction apart from relief of pain, or may be accompanied by other pharmaceutical effects as to create a wanting of the opioid agonist analgesic as an issue separate and distinct from the issue of pain relief. It is undesirable for a human patient to want to be administered an opioid agonist analgesic for reasons other than relief of pain or prescribed treatment of licit medical maladies such as loose stool. Such a wanting could result in the opioid agonist analgesic being administered in quantities greater than that required to treat pain and other licit medical maladies, which would result in waste of opioid agonist analgesic, and an increase in spending for opioid agonist analgesics. This is of great societal significance in managing the allocation of scarce resources available in the treating health care system in general. Any wastage of money on a pharmaceutical or medication results in less money available for other needed resources, be they other medications or health care services. In and of itself, a decrease in wanting of opioids apart from pain relief and other licit uses (hereafter "any licit use") would be of great of great utility, whether it be in an opioid na ve individual (i.e., one that has not been previously exposed to opioid analgesics) or an individually chronically exposed to opioid agonist analgesics (e.g., a chronic pain patient, as one who is long suffering from malignant or cancer-related pain). There have been attempts to reduce the effective amount of opioid agonist analgesic for any licit use. Such attempts have included the co-administration of opioids with NMDA-receptor antagonists or relatively low doses of opioid antagonist. These methods, if effective, could theoretically serve the desired purpose of reducing wastage of opioids, however these methods have not been demonstrated to decrease the wanting of the opioid apart from any licit use, and in fact, could theoretically potentiate the opioid agonist effect to possibly increase
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the wanting desire of the opioid agonist analgesic, which would have the opposite of the desired effect to decrease wastage and optimize management of scare health care resources. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Prevention and treatment of functional somatic disorders, including stress-related disorders Inventor(s): Kranzler, Jay D.; (LaJolla, CA), Rao, Srinivas G.; (San Diego, CA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20030232805 Date filed: April 24, 2003 Abstract: Methods for the prevention or treatment of stress-related disorders by administering a therapeutically effective amount of a dual serotonin/norepinephrine reuptake inhibitor to an individual under stress are described. A triple monoamine reuptake inhibitor for serotonin/noradrenaline/dopamine may also be administered to an individual at risk for a stress-related disorder. In a preferred embodiment the compound is milnacipran and is prophylactically administered at an effective amount to delay or prevent stress-related disorders in an individual at risk. Excerpt(s): This application claims priority to U.S. Ser. No. 60/375,068 entitled "Methods of treating Functional Somatic Disorders" filed Apr. 24, 2002 by Jay D. Kranzler and Srinivas G. Rao and to U.S. Ser. No. ______ entitled "Prevention and Treatment of StressRelated Disorders" filed Apr. 18, 2003, Jay D. Kranzler and Srinivas G. Rao. The present invention relates to a method of preventing or treating functional somatic disorders (FSD), including stress-related disorders (SRD). In one particular aspect, the present invention relates to methods of treating or preventing functional somatic disorders with dual serotonin norepinephrine reuptake inhibitors that also have NMDA antagonistic activity. In another aspect, the present invention relates to methods of treating FSD in a person having one or more symptoms of FSD by simultaneously treating at least one somatic symptom and one central nervous system (CNS) symptom of the FSD. In a preferred embodiment, the present invention relates to methods of preventing or treating SRD with dual serotonin/norepinephrine reuptake inhibitors. Stress-related disorders (SRD) are the cause of seventy-five to ninety percent of office visits to physicians. Stress can affect the onset of, or susceptibility to disease. It can also affect the progression or course of disease even when there is another underlying pathophysiology of the disease. Recovery from an existing disease can also be delayed due to stress. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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REGULATION OF TYROSINE HYDROXYLASE BY GPE Inventor(s): Alexi, Tajrena; (Auckand, NZ), Gluckman, Peter D.; (Auckland, NZ), Guan, Jian; (Auckland, NZ) Correspondence: Sheldon R. Meyer; Fliesler Dubb Meyer & Lovejoy Llp; Suite 400; Four Embarcadero Center; San Francisco; CA; 94111-4156; US Patent Application Number: 20040087487 Date filed: June 26, 2003 Abstract: Embodiments of this invention include methods for increasing the amount of the enzyme tyrosine hydroxylase (TH) in the central nervous system (CNS) of mammals in need of an increase in TH. Methods include the use of the tripeptide, gly-pro-glu (GPE) to increase TH in the CNS. GPE can increase the amount of TH and/or decrease the loss of TH in conditions characterized by a loss of dopamine, such as Parkinson's disease and CNS injury. GPE may act to increase the expression of TH or by inhibiting a decrease in TH expression within the CNS or by inhibiting the loss of TH-containing neurons within the CNS. By increasing the amounts of TH in the CNS, GPE can increase the amount of the neurotransmitter, dopamine, in areas of the CNS responsible for adverse symptoms of neural injury or disease. Excerpt(s): This invention relates to methods of regulating the effect of tyrosine hydroxylase (TH). In particular it relates to increasing the effective amount of TH in the central nervous systems (CNS) for the purpose of increasing TH-mediated dopamine production in the treatment of conditions such as Parkinson's disease. Parkinson's disease is the second most prevalent neurodegenerative disorder after Alzheimer's. It is a chronic and progressive motor system disorder and is distinguished by a tremor at rest, muscular rigidity, a slowness of movement initiation and movement execution and a mask-like appearance to the face. The cause of this disease is unknown but the symptoms are a consequence of an 80% or greater loss of the dopaminergic neurons (which produce dopamine) in the pars compacta region of the substantia nigra (SNc). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension Inventor(s): Blaine, Edward H.; (University City, MO), Koepke, John P.; (St. Louis, MO), Manning, Robert E.; (St. Louis, MO), Reitz, David B.; (Chesterfield, MO), Schuh, Joseph R.; (St. Louis, MO), Smits, Glenn J.; (Ellisville, MO) Correspondence: J. Timothy Keane; Pharmacia Corporation; Corporate Patent Department; 800 North Lindbergh BLVD., Mail Zone O4e; ST. Louis; MO; 63167; US Patent Application Number: 20030220521 Date filed: May 20, 2002 Abstract: Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine.beta.-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical
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moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-.beta.-hydroxylase inhibitors, of which N-acetyl-.gamma.glutamyl fusaric acid hydrazide (shown below) is preferred. 1 Excerpt(s): This application is a continuation-in-part of U.S. Application Ser. No. PCT/US90/04168 filed Jul. 25 1990, which is a continuation-in-part of U.S. application Ser. No. 07/386,527 filed Jul. 27 1989. This invention is in the field of cardiovascular therapeutics and relates to a class of compounds useful in control of hypertension. Of particular interest is a class of compounds which prevent or control hypertension by selective action on the renal sympathetic nervous system. Hypertension has been linked to increased sympathetic nervous system activity stimulated through any of four mechanisms, namely (1) by increased vascular resistance, (2) by increased cardiac rate, stroke volume and output, (3) by vascular muscle defects or (4) by sodium retention and renin release [J. P. Koepke et al, The Kidney in Hypertension, B. M. Brenner and J. H. Laragh (Editors), Vol. 1, p. 53 (1987)]. As to this fourth mechanism in particular, stimulation of the renal sympathetic nervous system can affect renal function and maintenance of homeostasis. For example, an increase in efferent renal sympathetic nerve activity may cause increased renal vascular resistance, renin release and sodium retention [A. Zanchetti et al, Handbook of Hypertension, Vol. 8, Ch. 8, vasoconstriction has been identified as an element in the pathogenesis of early essential hypertension in man. [R. E. Katholi, Amer. J. Physiol., 245, F1-F14 (1983)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tetrahydroisoquinoline derivatives as modulators of dopamine D3 receptors Inventor(s): Branch, Clive Leslie; (Bishops Stortford, GB), Johnson, Christopher Norbert; (Saffron Walden, GB), Stemp, Geoffrey; (Bishops Stortford, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030191314 Date filed: February 14, 2003 Abstract: Compounds of formula (I): 1wherein:R.sup.1 represents a substituent selected from: a hydrogen or halogen atom; a hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, pentafluoroethyl, C.sub.1-4alkyl, C.sub.1-4alkoxy, arylC.sub.1-4alkoxy, C.sub.1-4alkylthio, C.sub.1-4alkoxyC.sub.1-4alkyl, C.sub.3-6cycloalkylC.sub.1-4alkoxy, C.sub.1-4alkanoyl, C.sub.1-4alkoxycarbonyl, C.sub.1-4alkylsulfonyl, C.sub.1-4alkylsulfonyloxy, C.sub.1-4alkylsulfonylC.sub.1-4alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC.sub.1-4alkyl, C.sub.1-4alkylsulfonamido, C.sub.1-4alkylamido, C.sub.1-4alkylsulfonamidoC.sub.1-4alkyl, C.sub.14alkylamidoC.sub.1-4alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC.sub.14alkyl, arylcarboxamidoC.sub.1-4a- lkyl, aroyl, aroylC.sub.1-4alkyl, or arylC.sub.14alkanoyl group; a group R.sup.3OCO(CH.sub.2).sub.p, R.sup.3CON(R.sup.4)(CH.sub.2).sub.p, R.sup.3R.sup.4NCO(CH.sub.2).sub.p or R.sup.3R.sup.4NSO.sub.2(CH.sub.2).su- b.p where each of R.sup.3 and R.sup.4 independently represents a hydrogen atom or a C.sub.1-4alkyl group or R.sup.3R.sup.4
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forms part of a C.sub.3-6azacyloalkane or C.sub.3-6(2-oxo)azacycloalkane ring and p represents zero or an integer from 1 to 4; or a group Ar.sup.1--Z, wherein Ar.sup.1 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6membered aromatic heterocyclic ring and Z represents a bond, O, S , or CH.sub.2;R.sup.2 represents a hydrogen atom or a C.sub.1-4alkyl group;q is 1 or 2;A represents a group of formula (a) or (b) 2whereinT, U, V and Y independently represent CH or a nitrogen atom;R.sup.5 is a group selected from: a hydrogen or halogen atom, cyano, C.sub.1-4 alkyl or C.sub.1-4 alkoxy groups is 1 or 2.Ar.sup.2 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring; and salts thereof. The compounds are useful for the treatment of conditions which require modulaton of a dopamine receptor such as schizophrenia. Excerpt(s): The present invention relates to novel tetrahydroisoquinoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D.sub.3 receptors, in particular as antipsychotic agents. is an optionally substituted thienyl or optionally substituted phenyl ring; R.sup.1, R.sup.2 and R.sup.3 are each inter alia hydrogen; X is inter alia (CH.sub.2)mNR.sup.7CO; m is 2-4; and Ar.sup.1 is an optionally substituted heterocyclic ring or an optionally substituted phenyl ring. The compounds are said to be useful as antiarrhythmic agents. The compounds are said to be dopaminergic agents useful as antipsychotics, antihypertensives and also of use in the treatment of hyperprolactinaemia-related conditions and several central nervous system disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Transdermal therapeutic system Inventor(s): Gunther, Clemens; (Berlin, DE), Horowski, Reinhard; (Berlin, DE), Tack, Johannes; (Berlin, DE), Windt-Hanke, Fred; (Berlin, DE) Correspondence: Wood Phillips Katz Clark & Mortimer; Suite 3800; 500 West Madison Street; Chicago; IL; 60661-2511; US Patent Application Number: 20040101550 Date filed: July 7, 2003 Abstract: Use of a transdermal therapeutic system (TTS) comprising a pharmaceutical layer containing at least one matrix having an active ingredient and/or an active ingredient reservoir; a diffusion barrier that is permeable to said active ingredient and arranged on the skin side of the active ingredient reservoir; and an ergoline derivative or salt thereof as an active ingredient for producing an agent for obtaining and maintaining the circadian rhythm under dopamine therapy. Excerpt(s): This invention relates to a transdermal therapeutic system (TTS) comprising a pharmaceutical layer containing at least one matrix having an active ingredient and/or an active ingredient reservoir; a diffusion barrier that is permeable to said active ingredient and arranged on the skin side of the active ingredient reservoir; and an ergoline derivative or salt thereof as an active ingredient for producing an agent for obtaining and maintaining the circadian rhythm under dopamine therapy. The term "TTS" mostly denotes percutaneously acting but also transmucosal systems. A TTS typically has a sheet-like structure and is attached to an area of the skin. The system can optionally be attached to the skin by an additional skin-side adhesive that is permeable to the active ingredient. Alternatively, the matrix and/or diffusion barrier can itself have
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adhesive properties. And finally a non-adhesive TTS can be attached to the skin using other auxiliary means such as adhesive tapes or bandages. The matrix is a material in which the active ingredient is immobilized. An active agent in an active ingredient reservoir however is not necessarily immobilized, which is why the active ingredient reservoir must be enclosed. The diffusion barrier forms the skin-side portion of this shell. It goes without saying that all other parts of the shell should be as impermeable as possible, including diffusion paths, to the active ingredient. Immobilized means in this context that any uncontrolled active ingredient flow is prevented. However diffusion of an active agent in a matrix and/or through a diffusion barrier is not only possible but intended. The diffusion coefficients eventually determine the active ingredient flux from the TTS into a patient's skin. The dose released into a patient's skin is in first approximation a linear function of the active area of the TTS. The active area is the contact area of those TTS portions that allow active ingredient diffusion. TTSs can be used in human and veterinary medicine. A TTS of the design mentioned above is known in principle from publication WO 92/20339. It specifically describes the effect of propylene glycol lauric acid on the flux, i.e. a considerable increase in flux. However the values specified therein relate to solutions applied to skin samples and not to the actual TTS. No specification is given regarding flux from a TTS. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of disorders secondary to organic impairments Inventor(s): Mueller, Peter Sterling; (Princeton, NJ) Correspondence: Hoffmann & Baron, Llp; 6900 Jericho Turnpike; Syosset; NY; 11791; US Patent Application Number: 20030207943 Date filed: April 17, 2001 Abstract: A method for treatment of neuropsychiatric symptoms or disorders emanating from primary brain or systemic impairments includes administration of an effective dose of a dopamine, serotonin, and norepinephrine reuptake inhibitor to a human in need of such treatment. The preferred reuptake inhibitor is sibutramine. Excerpt(s): This application is a continuation-in-part application of U.S. application Ser. No. 09/204,124 filed Dec. 2, 1998. The present invention relates to the pharmacological treatment of various secondary neurological, behavioral and cognitive symptoms or disorders emanating out of brain or systemic impairments, i.e, primary impairments. The secondary symptoms and disorders include as non-limiting examples, tic and behavioral disorders including Tourette's syndrome and severe non-Tourette's motor or vocal tics; Posttraumatic Stress Disorder (PTSD); a typical attention deficit disorder with or without hyperactivity; frontal lobe defects of executive function; oscillopsia; selfmutilation; violence or rage such as in intermittent explosive disorder; asocial behavior; sexual disorders (including gender choice difficulties or hyposexuality); psychological (psychosis, violence, and confusion) and motor symptoms of Huntington's Disease (Huntington's Chorea); fatigue, exhaustion, sleep problems, and pain of Chronic Fatigue Syndrome with or without Fibromyalgia; psychosis with multiple hallucinations and delusions secondary to brain injury; opiate narcotic addiction; Sick Building Syndrome (SBS); Gulf War Syndrome (GWS); Reflex Sympathetic Dystophy Syndrome (RSDS), also known as Complex Regional Pain Syndrome (CRPS); and Retinitis Pigmentosa (RP). It should be noted that a symptom is a single manifestation while a disorder involves more than one symptom or a cluster of symptoms.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of parkinson's disease by the combined action of a compound with neurotrophic activity and a compound enhancing the dopamine activity Inventor(s): Moller, Arne; (Sjaellands Odde, DK), Olsen, Gunnar M.; (Frederiksberg, DK), Peters, Dan; (Malmo, DK), Ronn, Lars Christian; (Vekso, DK) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040063742 Date filed: October 23, 2003 Abstract: This invention relates to the use of the combined action of a compound with neurotrophic activity and a compound enhancing the dopamine activity for the treatment of Parkinson's disease. Excerpt(s): Parkinson's disease is a neurodegenerative disease characterised by the progressive deterioration of motor skills, affecting about 4 million people worldwide. Parkinson's patients suffer from increasing difficulties in initiating movement, rigidity in arms and legs, as well as tremors. Although the specific cause of Parkinson's disease is unknown, it has been shown that the disease is associated with the degeneration of specific dopamine-containing neurons in a region of the brain known as the substanta nigra, which is believed to be involved in the coordination of movement. One existing treatment is L-DOPA therapy, alone or combined with e.g. dopamine agonists. However, after three to five years of L-DOPA therapy, involuntary motor disturbances (dyskinesia) may appear. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of compounds having combined dopamine d2, 5-ht1a and alpha adrenoreceptor agonistic action for treating cns disorders Inventor(s): Feenstra, Roelof W.; (Weesp, NL), Long, Stephen K.; (Weesp, NL), van der Heijden, Johannes A.M.; (Weesp, NL), van Scharrenburg, Gustaaf J.M.; (Weesp, NL) Correspondence: Finnegan Henderson Farabow; Garrett & Dunner; 1300 I Street NW; Washington; DC; 20005-3315; US Patent Application Number: 20030186838 Date filed: November 12, 2002 Abstract: The invention relates to the use of compounds having combined sopamine D.sub.2 agonistic activity, 5-HT.sub.1A agonistic activity and a adrenoceptor agonistic activity for the treatment of CNS disorders such as Parkinson's disease. Excerpt(s): The invention relates to the use of compounds having combined dopamine D.sub.2-agonistic activity, 5-HT.sub.1A agonistic and a adrenoceptor agonistic activity for the preparation of pharmaceutical compositions for the treatment of CNS disorders such as Parkinson's disease. WO99/62902 describes the use of compounds having affinity for the dopamine D.sub.2-receptor and/or the 5-HT.sub.1A receptor and/or the.alpha.sub.1-adrenoceptor for the treatment of a large number of disorders, e.g. depression, anxiety, psychoses, obesity etc. The compounds described therein have significantly less affinity for the.alpha.sub.1-adrenoceptor than compounds previously
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described. This is said to be important as it is known in the art that.alpha.sub.1-receptor antagonism mediates serious side-effects such as hypertension, sedation and sexual dysfunction. It has now been found that compounds having combined dopamine D.sub.2-agonistic activity, serotonin 5-HT.sub.1A-agonistic activity and noradrenergic.alpha.sub.1-adrenoceptor agonistic activity are particularly useful for the treatment of CNS disorders. Such compounds allow for a more complete treatment of Parkinson's disease without mediating the serious side-effects of compounds having the.alpha.sub.1-adrenoceptor antagonistic activity component. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with dopamine, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “dopamine” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on dopamine. You can also use this procedure to view pending patent applications concerning dopamine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON DOPAMINE Overview This chapter provides bibliographic book references relating to dopamine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on dopamine include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “dopamine” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on dopamine: •
Cochlear Pharmacology and Noise Trauma: Proceedings of the Joint Symposium Organised by the European Commission Concerted Action Protection Against Noise and the Novartis Foundation Source: London, England: NRN Publications. 1999. 206 p. Contact: Available from NRN Publications. Institute of Laryngology and Otology, 330 Gray's Inn Road, London, WC1X 8EE, United Kingdom. 440 207 915 1590. PRICE: Contact publisher for current price. ISBN: 190174700x. Summary: This book reprints the Proceedings of the Joint Symposium on Cochlear Pharmacology and Noise Trauma, organized by the European Commission Concerted Action Protection Against Noise and the Novartis Foundation, held in London, England in May 1998. Excessive exposure to noise results in either direct mechanical damage to the sensitive cochlear structures or from metabolic overload due to overstimulation. The probability of acquiring a hearing impairment increases if noise exposure is combined
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with other factors such as chemicals, extreme temperatures, and vibration. The book includes 16 chapters that cover inner ear pharmacology and clinical implications; immunocytochemical clues to the handling of excitatory neurotransmitters in the cochlea; GABA, dopamine, and serotonin in cochlear innervation, specifically models of protection against neurotoxicity; oral magnesium used to reduce noise induced temporary and permanent hearing loss; medical treatment for acoustic trauma; strategies for preventing hearing loss; intervention possibilities for noise induced hearing loss; strategies for protection of the inner ear from noise induced hearing loss (NIHL); toluene and styrene induced hearing losses; mechanisms of ototoxicity by chemical contaminants; therapeutic strategies for improving cochlear blood flow; peripheral and central effects of noise exposure in rats as determined by electrophysiological methods; noise induced calcium increases and the outer hair cell; protection against cisplatin ototoxicity by melanocortins; and thoughts on the type of patients who could benefit from in situ pharmacology. Each chapter concludes with a reference list and with a brief reprint of the discussion that happened after each presentation. A subject index concludes the volume.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “dopamine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “dopamine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “dopamine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Advances in Dopamine Research by M. Kohsaka (Editor), Mutsutoshi Kosaka; ISBN: 0080273912; http://www.amazon.com/exec/obidos/ASIN/0080273912/icongroupinterna
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Age-Related Dopamine-Dependent Disorders: International Symposium on AgeRelated Monoamine-Dependent Disorders and Their Modulation by Gene and Gend by M. Segawa, Y. Nomura (Editor); ISBN: 3805559607; http://www.amazon.com/exec/obidos/ASIN/3805559607/icongroupinterna
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Brain Dopaminergic Systems: Imaging With Positron Tomography (Developments in Nuclear Medicine, Vol. 20) by J. C. Baron, et al; ISBN: 079231476X; http://www.amazon.com/exec/obidos/ASIN/079231476X/icongroupinterna
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Cardiovascular and Renal Actions of Dopamine by P. Soares-Da-Silva (Editor); ISBN: 0080422098; http://www.amazon.com/exec/obidos/ASIN/0080422098/icongroupinterna
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Cardiovascular Function of Peripheral Dopamine Receptors (Clinical Pharmacology, Vol 15) by J. Paul Hieble (Editor), P. J. Hieble; ISBN: 0824781007; http://www.amazon.com/exec/obidos/ASIN/0824781007/icongroupinterna
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Central and Peripheral Dopamine Receptors: Biochemistry and Pharmacology by Gian L. Gessa (Editor), et al; ISBN: 0387967362; http://www.amazon.com/exec/obidos/ASIN/0387967362/icongroupinterna
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Central D1 Dopamine Receptors (Advances in Experimental Medicine and Biology, 235) by Menek Goldstein, et al; ISBN: 030642925X; http://www.amazon.com/exec/obidos/ASIN/030642925X/icongroupinterna
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Continuous Dopamineragic Stimulation in Parkinson's Disease (Journal of Neural Transmission, Supplementum 27) by R. Horowski, et al; ISBN: 0387820345; http://www.amazon.com/exec/obidos/ASIN/0387820345/icongroupinterna
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D1: D2 Dopamine Receptor Interactions (Neuroscience Perspectives) by J.L. Waddington (Editor); ISBN: 0127290451; http://www.amazon.com/exec/obidos/ASIN/0127290451/icongroupinterna
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Dopamine; ISBN: 089004239X; http://www.amazon.com/exec/obidos/ASIN/089004239X/icongroupinterna
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Dopamine Agonist; ISBN: 1850701970; http://www.amazon.com/exec/obidos/ASIN/1850701970/icongroupinterna
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Dopamine and Mental Depression (Advances in the Biosciences, Vol 77) by G. Serra, Gian Luigi Gessa; ISBN: 0080407625; http://www.amazon.com/exec/obidos/ASIN/0080407625/icongroupinterna
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Dopamine and Neuroendocrine Active Substances by Emilio Del Pozo, et al; ISBN: 0122090454; http://www.amazon.com/exec/obidos/ASIN/0122090454/icongroupinterna
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Dopamine and Pituitary Hormones in Critical Illness by G. Van Den Berghe; ISBN: 9061865980; http://www.amazon.com/exec/obidos/ASIN/9061865980/icongroupinterna
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Dopamine Receptor Agonists (New Horizons in Therapeutics) by George Poste, Stanley T. Crooke (Editor); ISBN: 0306416549; http://www.amazon.com/exec/obidos/ASIN/0306416549/icongroupinterna
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Dopamine Receptor Sub-Types: From Basic Sciences to Clinical Applications (Biomedical and Health Research, V. 19) by Peter Jenner (Editor), R. Demirdamar (Editor); ISBN: 9051992912; http://www.amazon.com/exec/obidos/ASIN/9051992912/icongroupinterna
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Dopamine Receptors; ISBN: 0845137077; http://www.amazon.com/exec/obidos/ASIN/0845137077/icongroupinterna
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Dopamine Receptors by Carl Kaiser (Editor); ISBN: 084120781X; http://www.amazon.com/exec/obidos/ASIN/084120781X/icongroupinterna
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Dopamine Receptors (Receptor Biochemistry and Methodology, Vol 8) by Ian Creese (Editor), Claire Fraser (Editor); ISBN: 0471633275; http://www.amazon.com/exec/obidos/ASIN/0471633275/icongroupinterna
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Dopamine Receptors and Transporters: Pharmacology, Structure, and Function by Hyman B. Niznik (Editor); ISBN: 0824791584; http://www.amazon.com/exec/obidos/ASIN/0824791584/icongroupinterna
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Dopamine, Ageing and Diseases, Section 5/Endogenous Anorectics, Section 6/Prostanoids, Section 7; ISBN: 9630543370; http://www.amazon.com/exec/obidos/ASIN/9630543370/icongroupinterna
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Dopaminergic mechanisms in vision; ISBN: 0845127470; http://www.amazon.com/exec/obidos/ASIN/0845127470/icongroupinterna
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Dopaminergic Mechanisms in Vision (Neurology and Neurobiology, Vol 43) by Ivan Bodis-Wollner; ISBN: 0471500364; http://www.amazon.com/exec/obidos/ASIN/0471500364/icongroupinterna
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Dopaminergic System: Evolution from Biological to Clinical Aspects by Liana Bolis (Editor), et al; ISBN: 0781732662; http://www.amazon.com/exec/obidos/ASIN/0781732662/icongroupinterna
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Dopaminergic Systems and Their Regulation; ISBN: 0895735094; http://www.amazon.com/exec/obidos/ASIN/0895735094/icongroupinterna
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Dopaminergic Systems and Their Regulation (Satellite Symposia of the Iuphar 9th International Congress of pharmacology) by G. N. Woodruff, et al; ISBN: 0895735091; http://www.amazon.com/exec/obidos/ASIN/0895735091/icongroupinterna
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Lisuride and other dopamine agonists : basic mechanisms and endocrine and neurological effects; ISBN: 0890048673; http://www.amazon.com/exec/obidos/ASIN/0890048673/icongroupinterna
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Mesolimbic Dopamine System: From Motivation to Action by Paul Willner (Editor), et al; ISBN: 0471928860; http://www.amazon.com/exec/obidos/ASIN/0471928860/icongroupinterna
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Multiple Dopamine Receptors: Receptor Binding Studies in Dopamine Pharmacology (Receptors and Ligands in Intercellular Communication Ser, Vol 1) by Milton Titeler; ISBN: 082471735X; http://www.amazon.com/exec/obidos/ASIN/082471735X/icongroupinterna
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Neurobiology of Central D1-Dopamine Receptors (Advancement in Experimental Medicine and Biology, 204) by George R. Breese, Ian Creese (Editor); ISBN: 0306423839; http://www.amazon.com/exec/obidos/ASIN/0306423839/icongroupinterna
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Neurobiology of Dopamine by A.S. Horn (Editor); ISBN: 0123541506; http://www.amazon.com/exec/obidos/ASIN/0123541506/icongroupinterna
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Nonstriatal dopaminergic neurons by Erminio Costa, G. L. Gassa; ISBN: 089004127X; http://www.amazon.com/exec/obidos/ASIN/089004127X/icongroupinterna
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Peripheral Dopamine Pathophysiology by Francesco M.D. Amenta (Editor); ISBN: 0849369495; http://www.amazon.com/exec/obidos/ASIN/0849369495/icongroupinterna
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Psychology Video Lab One: The Role of Dopamine in the Regulation of Motor and Aggressive Behaviors by Richard A. Deyo; ISBN: 0205267882; http://www.amazon.com/exec/obidos/ASIN/0205267882/icongroupinterna
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The Mesocorticolimbic dopamine system; ISBN: 089766471X; http://www.amazon.com/exec/obidos/ASIN/089766471X/icongroupinterna
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The Mesocorticolimbic Dopamine System (Annals of the New York Academy of Sciences, Vol 537) by Peter W. Kalivas, Charles B. Nemeroff (Editor); ISBN: 0897664701; http://www.amazon.com/exec/obidos/ASIN/0897664701/icongroupinterna
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The Neurobiology of Dopamine Systems (Studies in Neuroscience) by W. Winlow, et al; ISBN: 0719017998; http://www.amazon.com/exec/obidos/ASIN/0719017998/icongroupinterna
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The Role of Brain Dopamine (Basic and Clinical Aspects of Neuroscience, Vol 3) by P. Riederer; ISBN: 0387500405; http://www.amazon.com/exec/obidos/ASIN/0387500405/icongroupinterna
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Chapters on Dopamine In order to find chapters that specifically relate to dopamine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and dopamine using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “dopamine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on dopamine: •
Motor Disorder of Alzheimer's Dementia: Clinical and PET Studies Source: in Battistin, L.; Gerstenbrand, F., eds. Aging Brain and Dementia: New Trends in Diagnosis and Therapy. Proceedings of A Symposium held in Padova, Italy, September 22-24, 1988. New York, NY: Alan R. Liss, Inc. 1990. p. 371-380. Contact: Available from Alan R. Liss, Inc. 41 East 11th Street, New York, NY 10003. (212) 741-2515. ISBN: 0471562114. Summary: Dementia of the Alzheimer type (DAT) may present clinically in a number of ways. The association of signs that are similar to or indistinguishable from those of Parkinson's disease with Alzheimer's disease leads to the question of the involvement of the dopaminergic system in this disorder. The fact that it was reported that in vivo cerebrospinal fluid analysis indicated a reduction in dopamine and its metabolite (homovanillic acid) in patients scored for the presence of rigidity underlines the fact that careful clinical selection of patients may be needed to make sense of neurochemical and histopathologic changes in the dopaminergic system in DAT. This paper reports the design and results of a study that sought to correlate clinical features with in vivo measurements of the dopaminergic system, using positron emission tomography (PET). Preliminary results are reported on a small number of patients. 26 references.
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Hiccups: Reasons and Remedies Source: in Lewis, J.H., ed. Pharmacologic Approach to Gastrointestinal Disorders. Baltimore, MD: Williams and Wilkins. 1994. p. 209-227. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4000. Fax (410) 528-4414. PRICE: $85 (as of 1995). ISBN: 0683049704. Summary: In this chapter, from a book on the pharmacologic approach to gastrointestinal disorders, the author explains the pathophysiology of hiccups. The author describes nonpharmacologic treatments first because most individuals attempt a physical or mechanical maneuver to stop hiccups before drug therapy. Specific topics include hiccup frequency; conditions associated with hiccups; hiccups due to anesthesia and surgery; hiccup epidemics; gastrointestinal causes of hiccups; historical cures; the physical and mechanical means of treating hiccups; and drug therapy for hiccups, including the use of major tranquilizers, anticonvulsants, central nervous system stimulants, sedatives, hypnotics, muscle relaxants or antispasticity agents, narcotic analgesics, tricyclic antidepressants, calcium channel blocking agents, dopamine antagonists, dopamine agonists, parasympathomimetics, serotonin antagonists, and lidocaine; and guidelines for treating transient and persistent hiccups. 5 tables. 126 references.
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Neurotransmitter Receptors in Normal Human Aging and Alzheimer's Disease Source: in Sen, A.K. and Lee, T., eds. Receptors and Ligands in Neurological Disorders. New York, NY: Cambridge University Press. 1988. p. 120-147. Contact: Available from Cambridge University Press. 40 West 20th Street, New York, NY 10011-4211. (800) 872-7423; (212) 924-3900; FAX (212) 691-3239. PRICE: $92.50. ISBN: 0521307201. Summary: This book chapter focuses exclusively on changes in brain neurotransmitter receptors associated both with normal (non-pathological) human aging and with Alzheimer's disease (AD). Specific attention is given to two principal areas: considerations in experimental design (saturation analyses, normalization, multiple tissue sources, donor criteria, premorbid state, psychoactive drug history, postmortem interval and tissue storage, and neuropathological diagnosis) and specific changes in receptor binding properties with normal aging and with AD (acetylcholine, serotonin, adrenergic, dopamine, and GABA receptors, and excitatory amino acids). Future prospects concerning studies of receptor binding also are discussed. 56 references.
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Effect of Malnutrition and of Changes in Protein Intake on Renal Function Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 229-244. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on the effect of malnutrition and of changes in protein intake on renal function is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The author notes that protein is an important modulator of renal hemodynamics. A prolonged change from a low to a high protein diet increases renal blood flow and glomerular filtration rate (GFR) by as much as 30 to 60 percent. The author discusses the mechanisms, which may not be mutually exclusive, that have been proposed to explain this increase in renal blood flow and GFR observed after a protein meal or during chronic protein administration. First, humoral factors, either circulating or local, are released in response to elevation in plasma amino acid levels and subsequently stimulate renal vasodilation. An increase in protein intake stimulates the secretion of growth hormone, glucagon, dopamine, eicosanoids, and renin. Second, a role for amino acids as metabolic substrates in causing these changes has been suggested. Third, intrinsic renal mechanisms including tubuloglomerular feedback and tubular transport mechanisms may be involved. The author then focuses on chronic calorie-protein malnutrition and its effects on renal function. The decrease in GFR and the increased reabsorption of solutes observed in malnourished individuals would tend to minimize the loss of nutrients in the urine. In addition, the fall in the filtered load of sodium would decrease the metabolic requirements for sodium reabsorption in the kidney and hence lower the basal metabolic requirement in patients with chronic protein energy malnutrition. 2 figures. 1 table. 68 references. (AA-M).
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Chapter 67: Movement Disorders Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 13 p.
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Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides information on the symptoms, diagnosis, and treatment of various movement disorders, including tremors, cramps, myoclonus, hiccups, Tourette's syndrome, chorea, athetosis, Huntington's disease, dystonia, Parkinson's disease, progressive supranuclear palsy, Shy-Drager syndrome, and coordination disorders. Damage to or an abnormality of an area of the nervous system that regulates movement may cause a person to experience a movement disorder. A tremor is an involuntary, rhythmic, shaking movement that occurs when muscles repeatedly contract and relax. Types of tremors include action, resting, intention, essential, senile, and familial tremors. Although treatment is usually not needed for movement disorders, drugs may be helpful for some people. A cramp is a sudden, brief, usually painful contraction of a shortened muscle or group of muscles. Cramps are common in healthy people and do not need to be treated. Myoclonus causes a synchronous quick jerk of affected muscles. Antiseizure drugs may be used to treat severe cases of myoclonic jerks. Hiccups are repeated spasms of the diaphragm followed by quick, noisy closings of the glottis. They are caused when a stimulus triggers the nerves that contract the diaphragm. Most cures for hiccups require holding the breath to increase the amount of carbon dioxide in the blood. Stimulating the vagus nerve may also help. Tourette's syndrome is a hereditary disorder characterized by motor and vocal tics. Antipsychotic drugs may help suppress them. Chorea and athetosis are symptoms that can result from several different diseases, including Huntington's disease and Sydenham's disease. Drugs that block the action of dopamine may help control abnormal movements. Huntington's disease is an inherited disease characterized by abnormal movements and gradual loss of brain cells. There is no cure for Huntington's disease, but drugs may help relieve symptoms and control behavior. In people who have dystonia, muscles may freeze in the middle of an action. Dystonia seems to be caused by overactivity in several areas of the brain. Types of dystonia are idiopathic torsion dystonia, blepharospasm, torticollis, and spasmodic dysphonia. Treatment is limited. Drugs with anticholinergic properties may be helpful. Parkinson's disease is a progressive, degenerative disorder of the nervous system. Although the cause of nerve cell degeneration and dopamine loss is usually not known, Parkinson's disease is sometimes a very late complication of viral encephalitis or a complication of using certain drugs. Muscle stiffness develops in Parkinson's disease, and initiating a movement is difficult. Various drugs are used to treat this disease, including levodopa, bromocriptine, pergolide, selegiline, anticholinergics, antihistamines, antidepressants, propranolol, and amantadine. Progressive supranuclear palsy causes muscle rigidity, inability to roll the eyes upward, and weakness of the throat muscles. The cause is unknown, and there is no completely effective treatment. Shy-Drager syndrome causes malfunction and destruction of the autonomic nervous system. Treatment is the same as for Parkinson's disease but includes the drug fludrocortisone. Coordination disorders occur when the cerebellum is damaged. •
Neurochemical, Genetic and Clinical Aspects of Alzheimer's Disease Source: in Bergener, M.; Ermini, M.; Stahelin, H.B. Dimensions in Aging. Orlando, FL: Academic Press Incorporated. 1986. p. 183-205. Contact: This book may be available from your local medical library. Call for information. ISBN: 012091625.
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Summary: This chapter summarizes and discusses various neurochemical, genetic, and clinical aspects of Alzheimer's disease (AD). Following a brief background discussion of AD and senile dementia, attention is given to: clinical and histopathological profiles of dementia disorders; neurotransmitter changes in AD, including acetylcholine, noradrenaline, serotonin, dopamine, and specificity effects; and molecular genetics studies, including those aimed at identifying the gene(s) involved in AD risk and RNA. It is concluded that, despite the advancement of a number of hypotheses concerning AD, many problems remain to be solved. A summary of some of these problems is included. 93 references. •
Gastroparesis, Nausea, and Vomiting Source: in Lewis, J.H., ed. Pharmacologic Approach to Gastrointestinal Disorders. Baltimore, MD: Williams and Wilkins. 1994. p. 131-162. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4000. Fax (410) 528-4414. PRICE: $85 (as of 1995). ISBN: 0683049704. Summary: This chapter, from a book on the pharmacologic approach to gastrointestinal disorders, explains gastroparesis, nausea, and vomiting. The author reviews the normal regulation of gastric motility and the mechanism of emesis production and covers diseases that may benefit from treatment including peptic ulcer disease, diabetes, collagen diseases, anorexia nervosa, postoperative ileus, tachygastria, short bowel syndrome, and pernicious anemia. The author also describes medications available for the treatment of vomiting and gastric stasis, including anticholinergic and cholinomimetic agents, histamine receptor antagonists, neuroleptic drugs, adrenergic blocking drugs, substituted benzamides acting at multiple receptor sites, dopamine antagonists, 5-HT3-receptor antagonists, specific 5-HT4-receptor agonists, opioid agonists and antagonists, and motilin analogs. 2 figures. 3 tables. 244 references. (AAM).
•
Urine Tests: Examining the Body's Excess Fluids Source: in Shaw, M., et al., eds. Everything You Need to Know About Medical Tests. Springhouse, PA: Springhouse Corporation. 1996. p. 549-616. Contact: Available from Springhouse Publishing. Attention: Trade and Textbook Department, 1111 Bethlehem Pike, P.O. Box 908, Springhouse, PA 19477-0908. (800) 3313170 or (215) 646-4670 or (215) 646-4671. Fax (215) 646-8716. PRICE: $24.95 (as of 1995). ISBN: 0874348234. Summary: This lengthy chapter, from a consumer handbook about medical practice and disease, presents information on urine tests used for diagnosis. Written in a question and answer format, the chapter discusses urine tests for these functions, diseases, and substances: kidney stones, kidney function, phosphate reabsorption by the kidneys, amylase, arysulfatase A, lysozyme, aldosterone, Cushing's syndrome, epinephrine, norepinephrine, dopamine, estrogens, pregnancy, placental estriol, pregnanetriol, vanillylmandelic acid, homovanillic acid, hydroxyindoleacetic acid, pregnanediol, proteins, Bence Jones protein, amino acid disorders, creatinine, creatinine clearance by the kidneys, urea clearance by the kidneys, uric acid, hemoglobin, myoglobin, porphyrins, delta-aminolevulinic acid, bilirubin, urobilinogen, sugar, glucose, ketones, vitamin B6, vitamin C, sodium, chloride, potassium, calcium, phosphates, magnesium, and iron. For each test discussed, the authors provide information about why the test is
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done, how the test is performed, what to do before the test, and what the results indicate.
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CHAPTER 7. PERIODICALS AND NEWS ON DOPAMINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover dopamine.
News Services and Press Releases One of the simplest ways of tracking press releases on dopamine is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “dopamine” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to dopamine. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “dopamine” (or synonyms). The following was recently listed in this archive for dopamine: •
Activation of dopamine receptor causes erections in rats Source: Reuters Industry Breifing Date: April 12, 2004
•
Regulation of dopamine varies in family members with Parkinson's disease Source: Reuters Medical News Date: October 21, 2003
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•
Rosiglitazone restores renal dopamine receptor function in hyperinsulinemic rats Source: Reuters Industry Breifing Date: December 31, 2002
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Dopamine receptor-interacting protein elevated in schizophrenic and bipolar patients Source: Reuters Medical News Date: December 16, 2002
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MDMA severely toxic to dopaminergic neurons at common "recreational" doses Source: Reuters Medical News Date: September 26, 2002
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Dopamine may be key to kicking the habit: study Source: Reuters Health eLine Date: September 04, 2002
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Key regulator of dopaminergic neurons decreased in brains of schizophrenics Source: Reuters Medical News Date: August 26, 2002
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Synuclein-protein complexes render dopamine neurotoxic Source: Reuters Medical News Date: May 31, 2002
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Ropinirole slows loss of dopamine function in Parkinson's disease patients Source: Reuters Medical News Date: April 16, 2002
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EMEA highlights somnolence risk of dopamine agonists Source: Reuters Industry Breifing Date: March 04, 2002
•
Prefrontal cortical activity and dopaminergic function linked in schizophrenia Source: Reuters Medical News Date: January 30, 2002 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal,
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nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “dopamine” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “dopamine” (or synonyms). If you know the name of a company that is relevant to dopamine, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “dopamine” (or synonyms).
Academic Periodicals covering Dopamine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to dopamine. In addition to these sources, you can search for articles covering dopamine that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for dopamine. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with dopamine. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to dopamine: Bromocriptine •
Systemic - U.S. Brands: Parlodel; Parlodel SnapTabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202094.html
Cabergoline •
Systemic - U.S. Brands: Dostinex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203584.html
Metoclopramide •
Systemic - U.S. Brands: Metoclopramide Intensol; Octamide; Reglan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202364.html
Pergolide •
Systemic - U.S. Brands: Permax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202451.html
Pramipexole •
Systemic - U.S. Brands: Mirapex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203739.html
Ropinirole •
Systemic - U.S. Brands: Requip http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203364.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.
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Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “dopamine” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 96498 512 863 26 1332 99231
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “dopamine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Dopamine In the following section, we will discuss databases and references which relate to the Genome Project and dopamine. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).21 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “dopamine” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for dopamine: •
Dopamine Beta-hydroxylase, Plasma Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=223360
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Dopamine Beta-hydroxylase, Plasma, Thermolability of Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=223380
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Dopamine Receptor D1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126449
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Dopamine Receptor D2 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126450
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Dopamine Receptor D3 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126451
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Dopamine Receptor D4 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126452
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Dopamine Receptor D5 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126453
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Dopamine Receptor-interacting Protein, 78-kd Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606092
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Solute Carrier Family 6 (neurotransmitter Transporter, Dopamine), Member 3 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126455 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “dopamine” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of 22
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “dopamine” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on dopamine can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to dopamine. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to dopamine. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “dopamine”:
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Amphetamine Abuse http://www.nlm.nih.gov/medlineplus/amphetamineabuse.html Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on dopamine. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Dopamine Receptors Implicated in Obesity Source: National Institute On Drug Abuse. February 1, 2001. Contact: 6001 Executive Boulevard, Bethesda, MD 20892. (301) 443-6245. Summary: This press release by the National Institute on Drug Abuse (NIDA), discusses an article in the medical journal, Lancet. The study found that a deficiency of dopamine in the brain may explain why some individuals engage in pathological overeating, resulting in severe obesity. Dopamine, a neurotransmitter in the brain, helps to regulate feelings of pleasure and modulates the rewarding properties of food. Dr. Jean-Jack Wang, leader of the study and the research team, believes that individuals deficient in dopamine receptors may need to eat more than people with higher dopamine levels to induce feelings of satisfaction and gratification. Dr. Wang notes that findings from the study 'suggest that developing a way to improve dopamine receptor function might lead to better treatment of obesity.' Presently, the 'most appropriate practical application of this finding is to urge overweight individuals to exercise,' according to Dr. Wang. The study also found that dopamine receptor availability was lower in obese than in control individuals and that body mass index (BMI) correlated negatively with the measure of dopamine receptors. Individuals with the lowest dopamine receptor values had the largest BMI.
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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to dopamine. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to dopamine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with dopamine. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about dopamine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at
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http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “dopamine” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “dopamine”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “dopamine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “dopamine” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
24
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
25
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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DOPAMINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acclimation: Adaptation of animals or plants to new climate. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acupuncture Therapy: Treatment of disease by inserting needles along specific pathways or meridians. The placement varies with the disease being treated. Heat or moxibustion and acupressure may be used in conjunction. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH]
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Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinomas: A malignant tumor of the epithelial cells of a gland which typically metastasizes by way of the lymphatics. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] Adrenergic Uptake Inhibitors: Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (antidepressive agents, tricyclic) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. [NIH] Adrenoreceptor: Receptors specifically sensitive to and operated by adrenaline and/or noradrenaline and related sympathomimetic drugs. Adrenoreceptor is an alternative name. [NIH]
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Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agmatine: Decarboxylated arginine, isolated from several plant and animal sources, e.g., pollen, ergot, herring sperm, octopus muscle. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]
Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes
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occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]
Amenorrhea: Absence of menstruation. [NIH]
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Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Neurotransmitters: Amino acids released by neurons as intercellular messengers. Among the amino acid neurotransmitters are glutamate (glutamic acid) and GABA which are, respectively, the most common excitatory and inhibitory neurotransmitters in the central nervous system. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amrinone: A positive inotropic cardiotonic agent with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell. Its therapeutic use in congestive heart or left ventricular failure is associated with significant increases in the cardiac index, reductions in pulmonary capillary wedge pressure and systemic vascular resistance, and little or no change in mean arterial pressure. One of its more serious side effects is thrombocytopenia in some patients. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU]
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Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery.
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Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidopaminergic: Preventing or counteracting (the effects of) dopamine. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are
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highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiparasitics: Drugs used to treat bacterial and parasitic infections and some cancers. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the
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physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from
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posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Athetosis: A derangement marked by ceaseless occurrence of slow, sinuous, writhing movements, especially severe in the hands, and performed involuntarily; it may occur after hemiplegia, and is then known as posthemiplegic chorea. Called also mobile spasm. [EU] Atony: Lack of normal tone or strength. [EU] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. [NIH] Avian: A plasmodial infection in birds. [NIH] Avoidance Learning: A response to a cue that is instrumental in avoiding a noxious experience. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Axotomy: Transection or severing of an axon. This type of denervation is used often in experimental studies on neuronal physiology and neuronal death or survival, toward an understanding of nervous system disease. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH]
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Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benserazide: An inhibitor of dopa decarboxylase that does not enter the central nervous system. It is often given with levodopa in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone. [NIH] Benzamides: Benzoic acid amides. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any
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living organism. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]
Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types,
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yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal
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functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbidopa: A peripheral inhibitor of dopa decarboxylase. It is given in parkinsonism along with levodopa to inhibit the conversion of levodopa to dopamine in the periphery, thereby reducing the peripheral adverse effects, increasing the amount of levodopa that reaches the central nervous system, and reducing the dose needed. It has no antiparkinson actions when given alone. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotid Body: A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the
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blood and plays a crucial role in their homeostatic control. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalepsy: A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with psychotic disorders (e.g., schizophrenia, catatonic), nervous system drug toxicity, and other conditions. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral
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proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial
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distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at
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cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromans: Benzopyrans saturated in the 2 and 3 positions. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of
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the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] CNS: Central nervous system. The brain and spinal cord. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic
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substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colostomy: An opening into the colon from the outside of the body. A colostomy provides a new path for waste material to leave the body after part of the colon has been removed. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Compacta: Part of substantia nigra. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as
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standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of
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gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that
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has ruptured and discharged its ovum. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]
Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyproheptadine: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [NIH]
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Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dark Adaptation: Adjustment of the eyes under conditions of low light. The sensitivity of the eye to light is increased during dark adaptation. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH]
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Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprenyl: Substance that blocks the breakdown of dopamine, thus preserving its availability in the striatum. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the
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abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic
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substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopa Decarboxylase: One of the aromatic-l-amino-acid decarboxylases, this enzyme is responsible for the conversion of dopa to dopamine. It is of clinical importance in the treatment of Parkinson's disease. EC 4.1.1.28. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a
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delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drip: The continuous slow introduction of a fluid containing nutrients or drugs. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]
symptoms
resulting
from
an
absent
or
Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may
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be read but not understood. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysphoria: Disquiet; restlessness; malaise. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability
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of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Electroretinogram: The electrical effect recorded from the surface of the eyeball and originated by a pulse of light. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH]
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Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei
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although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Ergot Alkaloids: Alkaloids isolated from the ergot fungus Claviceps purpurea (Hypocreaceae). The ergot alkaloids were the first alpha-adrenergic antagonists discovered, but side effects generally prevent their administration in doses that would produce more than a minimal blockade in humans. Their smooth muscle-stimulating activities may be attributed to alpha-agonistic properties, thus characterizing these alkaloids as a series of partial agonists. They have many clinical applications, notably in obstetrics and the treatment of migraine. (From Martindale, The Extra Pharmacopoeia, 28th ed, p662). [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [NIH] Evacuation: An emptying, as of the bowels. [EU]
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Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitatory Postsynaptic Potentials: Nerve potential generated by an excitatory depolarizing stimulation. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Exploratory Behavior: The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH]
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Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and
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stain uptake. [NIH] Fludrocortisone: A synthetic mineralocorticoid with anti-inflammatory activity. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and
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sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Fusaric Acid: A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits dopamine betahydroxylase, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis. [NIH] Gait: Manner or style of walking. [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA,
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bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestation period: The period of development of the young from the time of conception until birth. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to
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inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH]
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Guanine: One of the four DNA bases. [NIH] Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [NIH] Haematemesis: The vomiting of blood. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Handedness: Preference for using right or left hand. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated
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hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heparin-binding: Protein that stimulates the proliferation of endothelial cells. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin
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help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]
Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypericum: Genus of perennial plants in the family Clusiaceae (Hypericaceae). Herbal and homeopathic preparations are used for depression, neuralgias, and a variety of other conditions. Contains flavonoids, glycosides, mucilage, tannins, and volatile oils (oils, essential). [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH]
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Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricaemia: Excess of uric acid or urates in the blood; it is a prerequisite for the development or gout and may lead to renal disease. Called also uricacidaemia and, formerly, lithemia. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxic: Having too little oxygen. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It
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includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] Impulsive Behavior: An act performed without delay, reflection, voluntary direction, or obvious control in response to a stimulus. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH]
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Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH]
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Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [NIH]
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Kainate: Glutamate receptor. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Lassitude: Weakness; exhaustion. [EU] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with
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instincts in general that motivate behavior. [NIH] Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH]
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Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Loxapine: An antipsychotic agent used in schizophrenia. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy
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based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological
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color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is
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referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH]
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Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Mollusca: A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes Gastropoda, Bivalvia, Cephalopoda, Aplacophora, Scaphopoda, Polyplacophora, and Monoplacophora. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH]
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Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motilin: A 22-amino acid polypeptide (molecular weight 2700) isolated from the duodenum. At low pH it inhibits gastric motor activity, whereas at high pH it has a stimulating effect. [NIH]
Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Skills: Performance of complex motor acts. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscarinic Antagonists: Drugs that bind to but do not activate muscarinic cholinergic receptors (receptors, muscarinic), thereby blocking the actions of endogenous acetycholine or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. Antagonists that discriminate among the various muscarinic receptor subtypes and might allow better control of peripheral and central actions are under development. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH]
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Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutilation: Injuries to the body. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or
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stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Nearsightedness: The common term for myopia. [NIH] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]
Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH]
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Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neurotrophin 3: A neurotrophic factor involved in regulating the survival of visceral and proprioceptive sensory neurons. It is closely homologous to nerve growth factor beta and brain-derived neurotrophic factor. [NIH]
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Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitric-Oxide Synthase: An enzyme that catalyzes the conversion of L-arginine, NADPH, and oxygen to citrulline, nitric oxide, and NADP+. The enzyme found in brain, but not that induced in lung or liver by endotoxin, requires calcium. (From Enzyme Nomenclature, 1992) EC 1.14.13.39. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which
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the individual does not derive pleasure although it may provide a release from tension. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oculi: Globe or ball of the eye. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Nerve: The 1st cranial nerve. The olfactory nerve conveys the sense of smell. It is formed by the axons of olfactory receptor neurons which project from the olfactory epithelium (in the nasal epithelium) to the olfactory bulb. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the
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retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organic Chemicals: A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac
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pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatic Polypeptide: A 36-amino acid polypeptide with physiological regulatory functions. It is secreted by pancreatic tissue. Plasma pancreatic polypeptide increases after ingestion of food, with age, and in disease states. A lack of pancreatic polypeptide in the islets of Langerhans has been associated with the obese syndrome in rats and mice. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasympathetic Nervous System: The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. [NIH] Parasympathomimetics: Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (cholinesterase inhibitors). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (ganglionic stimulants) are not included here. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU]
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Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perch: A common name for fish belonging to the order Perciformes with many genera and species. [NIH] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]
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Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Perivascular: Situated around a vessel. [EU] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacology, Clinical: The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its
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pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylalanine Hydroxylase: An enzyme of the oxidoreductase class that catalyzes the formation of L-tyrosine, dihydrobiopterin, and water from L-phenylalanine, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause phenylketonurias and phenylketonuria, maternal. EC 1.14.16.1. [NIH] Phenylketonurias: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme phenylalanine hydroxylase or less frequently by reduced activity of dihydropteridine reductase (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; seizures; skin hypopigmentation; eczema; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952). [NIH] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physicochemical: Pertaining to physics and chemistry. [EU]
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Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary-Adrenal System: The interactions between the anterior pituitary and adrenal glands, in which corticotropin (ACTH) stimulates the adrenal cortex and adrenal cortical hormones suppress the production of corticotropin by the anterior pituitary. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH]
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Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH]
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Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH]
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Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the
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configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU]
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Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from
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otherwise wholesome air. [NIH] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Quinpirole: A dopamine D2/D3 receptor agonist. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor antagonist. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Rage: Fury; violent, intense anger. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH]
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Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Dopamine: Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. [NIH] Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for muscarine over nicotine. There are several subtypes (usually M1, M2, M3.) that are characterized by their cellular actions, pharmacology, and molecular biology. [NIH] Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]
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Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Remoxipride: An antipsychotic agent that is specific for dopamine D2 receptors. It has been shown to be effective in the treatment of schizophrenia. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH]
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Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retraction: 1. The act of drawing back; the condition of being drawn back. 2. Distal movement of teeth, usually accomplished with an orthodontic appliance. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversal Learning: Any situation where an animal or human is trained to respond differentially to two stimuli (e.g., approach and avoidance) under reward and punishment conditions and subsequently trained under reversed reward values (i.e., the approach which was previously rewarded is punished and vice versa). [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH]
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Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rolipram: A phosphodiesterase inhibitor with antidepressant properties. [NIH] Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport. [NIH]
Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]
Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizophrenia, Catatonic: A type of schizophrenia characterized by abnormality of motor behavior which may involve particular forms of stupor, rigidity, excitement or inappropriate posture. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH]
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Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH]
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Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotonin Agonists: Agents that have an affinity for serotonin receptors and are able to mimic the effects of serotonin by stimulating the physiologic activity at the cell receptors. These compounds are used as antidepressants, anxiolytics, and in the treatment of migraine. [NIH]
Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists. [NIH] Serotonin Uptake Inhibitors: Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the adrenergic uptake inhibitors also inhibit serotonin uptake; they are not included here. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as
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the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Social Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH]
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Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spiperone: A spiro butyrophenone analog similar to haloperidol and other related compounds. It has been recommended in the treatment of schizophrenia. [NIH] Splanchnic Circulation: The circulation of blood through the vessels supplying the abdominal viscera. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Startle Reaction: A complex involuntary response to an unexpected strong stimulus usually auditory in nature. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU]
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Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereotypy: Unvarying repetition or unvarying persistence. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other
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disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the
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nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tandem Repeat Sequences: Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (inverted tandem repeats). [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH]
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Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Tetrahydronaphthalenes: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds. [NIH]
Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and
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serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Time Perception: The ability to estimate periods of time lapsed or duration of time. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Transplantation: Transference of tissue within an individual, between individuals of the same species, or between individuals of different species. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH]
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Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of
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management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triad: Trivalent. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconditioned: An inborn reflex common to all members of a species. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH]
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Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urobilinogen: A colorless compound formed in the intestines by the reduction of bilirubin. Some is excreted in the feces where it is oxidized to urobilin. Some is reabsorbed and reexcreted in the bile as bilirubin. At times, it is re-excreted in the urine, where it may be later oxidized to urobilin. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is
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used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasodilator Agents: Drugs used to cause dilation of the blood vessels. [NIH] Vasopressor: 1. Stimulating contraction of the muscular tissue of the capillaries and arteries. 2. An agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU]
VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the
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tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH]
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X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
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INDEX 1 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine, 71, 218, 273 A Abdomen, 273, 284, 285, 316, 319, 332, 351, 358, 360 Abdominal, 4, 196, 273, 298, 317, 321, 332, 338, 350 Abdominal Pain, 273, 317, 321 Aberrant, 26, 34, 92, 273 Ablation, 67, 100, 273 Abscess, 273, 348 Acceptor, 273, 319, 331 Acclimation, 211, 273 Accommodation, 273, 326 Acetaldehyde, 273, 275, 299 Acetylcholine, 19, 46, 48, 77, 79, 192, 196, 219, 236, 238, 273, 289, 320, 328, 329, 332 Acetylcholinesterase, 71, 273 Acidosis, 142, 273 Acoustic, 148, 154, 155, 160, 167, 232, 273, 282 Actin, 73, 273, 325, 326 Action Potentials, 27, 42, 273 Acupuncture Therapy, 47, 273 Acute renal, 95, 137, 273 Acyl, 208, 209, 274 Adaptability, 274, 287, 288 Adaptation, 20, 42, 50, 61, 273, 274, 296, 329, 336 Adduct, 120, 274 Adenine, 274 Adenocarcinomas, 128, 274 Adenoma, 71, 274 Adenosine, 5, 49, 65, 72, 85, 86, 89, 90, 127, 128, 133, 134, 274, 282, 314, 335 Adenylate Cyclase, 19, 66, 70, 76, 85, 114, 274, 307 Adipose Tissue, 80, 274 Adjustment, 273, 274, 296 Adrenal Cortex, 274, 275, 304, 336, 339 Adrenal Glands, 274, 336 Adrenal Medulla, 72, 274, 287, 303, 329 Adrenaline, 181, 274 Adrenergic, 67, 73, 76, 191, 222, 236, 238, 274, 280, 299, 303, 304, 320, 335, 339, 348, 352 Adrenergic Antagonists, 274, 304
Adrenergic Uptake Inhibitors, 274, 348 Adrenoreceptor, 229, 274 Adsorption, 29, 275 Adsorptive, 275 Adverse Effect, 120, 138, 275, 280, 286, 291, 300, 349 Aerobic, 275, 323 Aerosol, 275, 352 Afferent, 43, 275, 316, 338, 348 Age of Onset, 275, 357 Agmatine, 61, 275 Akathisia, 275, 280 Akinesia, 23, 275 Alcohol Dehydrogenase, 130, 275 Aldehyde Dehydrogenase, 130, 275, 299 Aldosterone, 73, 77, 238, 275, 323 Alertness, 275, 288 Alexia, 276, 300 Algorithms, 276, 284 Alimentary, 276, 332 Alkaline, 273, 276, 277, 285 Alkaloid, 276, 285, 291, 324, 329, 336 Alkylating Agents, 24, 276 Alkylation, 24, 276 Alleles, 4, 92, 115, 276, 319 Allergen, 276, 297, 347 Allogeneic, 80, 276 Allylamine, 276, 277 Alpha-Linolenic Acid, 159, 276 Alternative medicine, 242, 276 Alternative Splicing, 57, 276, 340 Amantadine, 237, 276 Ambulatory Care, 276 Amenorrhea, 276, 278, 285 Amine, 164, 221, 222, 277, 312 Amino Acid Neurotransmitters, 20, 277 Amino Acid Sequence, 43, 277, 279, 305, 339 Amino Acids, 236, 277, 278, 281, 305, 328, 333, 337, 340, 346, 352, 356, 358 Aminolevulinic Acid, 238, 277 Ammonia, 277, 352, 358 Amplification, 36, 66, 277 Amrinone, 277, 323 Amygdala, 31, 38, 69, 154, 201, 277, 283, 319, 348, 354 Amylase, 238, 277 Amyloid, 93, 277
364
Dopamine
Anaesthesia, 95, 103, 277, 315 Anal, 142, 143, 191, 222, 278, 303, 306, 320 Analgesic, 185, 186, 223, 278, 285, 291, 302, 318, 324, 326, 330 Analog, 278, 350 Analogous, 9, 192, 278, 300, 337, 356 Anaphylatoxins, 278, 292 Anatomical, 11, 23, 30, 41, 46, 51, 93, 278, 282, 289, 294, 298, 315, 323, 346 Anemia, 40, 257, 278, 307, 334 Anesthesia, 111, 120, 123, 135, 186, 235, 278, 295, 301, 318, 338 Anesthetics, 278, 303 Aneurysm, 278, 280, 358 Angina, 278, 339 Angina Pectoris, 278, 339 Angiotensinogen, 278, 344 Anhydrous, 221, 278 Animal model, 20, 21, 22, 46, 59, 153, 278 Anions, 278, 317, 352 Anorexia, 168, 181, 193, 238, 278 Anorexia Nervosa, 168, 238, 278 Antagonism, 140, 209, 230, 278, 291 Anterior Cerebral Artery, 278, 289 Anterograde, 35, 65, 279 Antiallergic, 279, 295 Antiarrhythmic, 227, 279 Antibacterial, 279, 350 Antibiotic, 278, 279, 285, 327, 333, 350, 355 Antibodies, 57, 61, 68, 82, 188, 213, 279, 311, 313, 314, 324, 336 Antibody, 76, 118, 188, 275, 279, 284, 292, 311, 312, 315, 321, 324, 347, 350 Anticholinergic, 237, 238, 279 Anticoagulant, 279, 340 Anticonvulsant, 210, 279 Antidepressant, 25, 98, 163, 182, 279, 285, 307, 346 Antidopaminergic, 156, 279 Antiemetic, 279, 280, 299, 323 Antigen, 80, 188, 275, 279, 292, 312, 313, 314, 315, 321, 323, 347 Antigen-Antibody Complex, 279, 292 Antihypertensive, 279, 307, 333 Anti-infective, 279, 313, 317 Anti-inflammatory, 279, 281, 307, 310, 326 Anti-Inflammatory Agents, 279, 281 Antineoplastic, 276, 279, 309 Antineoplastic Agents, 276, 279 Antioxidant, 27, 118, 279, 281, 308, 331 Antiparasitics, 190, 280 Antipruritic, 280, 295
Antipsychotic Agents, 205, 227, 280, 299 Antipyretic, 280, 326 Antiseptic, 280, 287 Antiviral, 276, 280 Anus, 191, 222, 278, 280, 285, 292 Anxiety, 26, 31, 40, 85, 130, 168, 181, 199, 201, 213, 220, 221, 229, 275, 280, 329, 332, 339, 346 Anxiety Disorders, 220, 221, 280, 332 Anxiolytic, 223, 280 Aorta, 280, 286, 359 Aortic Aneurysm, 4, 280 Apathy, 280, 328 Apomorphine, 41, 111, 142, 156, 189, 200, 206, 219, 280 Aponeurosis, 280, 308 Apoptosis, 19, 37, 58, 93, 113, 150, 151, 156, 161, 165, 167, 176, 212, 280, 287 Aqueous, 24, 189, 219, 281, 283, 296, 302, 313 Arachidonic Acid, 281, 301, 318, 339 Arginine, 275, 278, 281, 329 Arterial, 103, 142, 276, 277, 281, 288, 294, 313, 340, 353 Arteries, 135, 280, 281, 284, 288, 294, 326, 341, 355, 359 Arterioles, 281, 284, 286, 358 Arteriovenous, 114, 281 Artery, 278, 281, 286, 294, 302, 306, 321, 323, 341 Ascorbic Acid, 142, 281, 313 Aseptic, 281, 331 Aspartate, 24, 28, 63, 132, 144, 281, 318, 335 Aspartic Acid, 23, 281 Aspirin, 144, 281 Assay, 13, 156, 190, 281 Astringent, 281, 287 Astrocytes, 212, 281, 320, 323, 324 Asymptomatic, 121, 281 Ataxia, 257, 281, 288, 354 Athetosis, 237, 282 Atony, 4, 282 ATP, 65, 274, 282, 299, 309, 335, 340, 356 Atrial, 282, 294, 353, 357 Atrioventricular, 282, 294 Atrium, 282, 286, 294, 357, 359 Atrophy, 54, 96, 138, 193, 213, 257, 282, 327 Attenuated, 14, 282 Atypical, 18, 56, 63, 67, 181, 200, 205, 282, 291, 335
365
Auditory, 148, 152, 153, 164, 282, 321, 338, 350, 358 Auditory nerve, 152, 282, 321 Autonomic Nervous System, 191, 218, 237, 282, 332, 334, 349, 352 Autoradiography, 9, 18, 37, 41, 50, 103, 282 Autoreceptors, 29, 41, 43, 70, 282 Avian, 177, 282 Avoidance Learning, 140, 282 Axons, 18, 43, 282, 297, 316, 327, 330, 331, 338 Axotomy, 68, 282 B Bacteria, 274, 275, 279, 282, 283, 297, 302, 303, 306, 308, 310, 323, 343, 347, 350, 355, 356, 358 Bacterial Physiology, 274, 283 Bactericidal, 283, 304 Basal Ganglia Diseases, 282, 283, 290, 314 Base, 194, 200, 274, 283, 296, 318, 337, 354 Behavioral Symptoms, 4, 21, 283 Benign, 274, 283, 308, 311 Benserazide, 104, 283 Benzamides, 50, 89, 238, 283 Beta-pleated, 277, 283 Bewilderment, 283, 293 Bilateral, 99, 283, 345 Bile, 283, 308, 313, 319, 351, 358 Bile Acids, 283, 308, 351 Bilirubin, 238, 283, 358 Binding Sites, 10, 24, 43, 45, 63, 70, 74, 88, 98, 106, 217, 283 Bioavailability, 210, 283 Biochemical, 20, 33, 34, 52, 58, 67, 85, 95, 116, 119, 127, 129, 133, 148, 174, 182, 214, 218, 276, 283, 306, 348 Biological therapy, 283, 310 Biological Transport, 283, 298 Biophysics, 6, 151, 161, 283 Biopolymers, 215, 283 Biosynthesis, 73, 74, 78, 155, 158, 281, 284, 307, 357 Biotechnology, 63, 91, 210, 242, 253, 255, 256, 257, 258, 284 Biphasic, 18, 52, 284 Bipolar Disorder, 121, 124, 182, 220, 284 Bladder, 284, 290, 293, 315, 325, 340, 344, 358 Blastocyst, 284, 293, 336 Blepharospasm, 237, 284 Bloating, 284, 308, 317, 321
Blood Cell Count, 284, 334 Blood Coagulation, 284, 286, 355 Blood Glucose, 284, 312 Blood Platelets, 284, 348 Blood pressure, 25, 218, 279, 284, 289, 313, 314, 324, 341, 348, 349 Blood vessel, 284, 286, 287, 289, 294, 302, 310, 317, 325, 333, 349, 351, 353, 355, 358, 359 Blood-Brain Barrier, 50, 284, 318 Blot, 284, 314 Blotting, Western, 284, 314 Body Fluids, 284, 285, 300, 349 Body Mass Index, 262, 284, 331 Bone Marrow, 77, 284, 309, 314, 320, 351 Bone Morphogenetic Proteins, 158, 285 Bowel, 191, 222, 278, 285, 316, 348, 351 Bowel Movement, 285, 351 Bradykinin, 285, 329 Brain Stem, 54, 285, 288, 332 Broad-spectrum, 285, 355 Bromocriptine, 77, 146, 237, 246, 285 Bronchi, 285, 303 Bronchial, 285, 312 Bronchitis, 285, 290 Bulimia, 285, 348 Bupivacaine, 285, 319 Buprenorphine, 9, 51, 285 Bupropion, 97, 105, 117, 211, 216, 285 Bypass, 135, 285 C Calcium, 12, 60, 67, 116, 173, 192, 232, 235, 238, 277, 285, 286, 292, 329, 349 Calmodulin, 50, 62, 286 Capillary, 277, 285, 286, 309 Capsules, 286, 300, 309 Carbidopa, 169, 170, 203, 286 Carbohydrate, 203, 204, 286, 337, 346 Carbon Dioxide, 237, 286, 296, 306, 336, 344, 359 Carcinogen, 274, 286 Carcinogenic, 276, 286, 316, 339, 351 Cardiac, 213, 226, 276, 277, 279, 286, 294, 299, 301, 303, 305, 319, 326, 331, 351 Cardiac Output, 286, 351 Cardiopulmonary, 122, 123, 158, 286 Cardiopulmonary Bypass, 122, 123, 158, 286 Cardioselective, 286, 339 Cardiotonic, 277, 286, 299, 323 Cardiovascular, 97, 213, 216, 226, 232, 277, 286, 318, 348, 349, 358
366
Dopamine
Cardiovascular System, 216, 286 Carotene, 286, 345 Carotid Body, 80, 116, 286, 289 Case report, 113, 121, 130, 287 Caspase, 67, 165, 287 Catalepsy, 18, 287 Catechol, 98, 99, 120, 140, 287 Catecholamine, 29, 78, 136, 213, 225, 287, 299, 334 Catheter, 185, 287, 317 Catheterization, 287, 317 Cations, 287, 317 Caudal, 287, 314, 329, 337 Caudate Nucleus, 32, 71, 162, 279, 283, 287, 295, 327, 329 Causal, 287, 303 Cell Adhesion, 125, 212, 287 Cell Adhesion Molecules, 212, 287 Cell Cycle, 287, 290, 295 Cell Death, 19, 35, 58, 106, 148, 280, 287, 327 Cell Differentiation, 287, 349 Cell Division, 37, 256, 282, 287, 288, 310, 321, 323, 336, 339, 347 Cell membrane, 24, 190, 283, 287, 297, 302, 305, 308, 335, 338 Cell proliferation, 288, 308, 349 Cell Respiration, 288, 323, 344 Cell Size, 288, 306 Cell Survival, 56, 157, 288, 310 Cell Transplantation, 23, 39, 288 Central Nervous System Diseases, 199, 288 Central Nervous System Infections, 288, 311 Central Nervous System Stimulants, 235, 288 Centrifugation, 288, 353 Cerebellar, 113, 193, 282, 288, 343, 357 Cerebellar Diseases, 282, 288, 357 Cerebellum, 237, 288, 337, 343 Cerebral Arteries, 288, 323 Cerebral Cortex, 64, 69, 73, 75, 216, 282, 288, 305, 306, 316, 342 Cerebral hemispheres, 283, 285, 288, 289, 353 Cerebral Infarction, 222, 288 Cerebrospinal, 10, 235, 289 Cerebrospinal fluid, 10, 235, 289 Cerebrovascular, 101, 193, 283, 289, 354 Cerebrum, 288, 289, 353, 357 Cervical, 72, 87, 289, 311, 356
Cervix, 289 Character, 278, 289, 296 Chemoreceptor, 280, 289 Chemotactic Factors, 289, 292 Chemotherapy, 4, 196, 289 Chin, 289, 322 Chlorpyrifos, 164, 289 Cholecystokinin, 66, 175, 289 Cholesterol, 283, 289, 294, 346, 351 Choline, 273, 289 Cholinergic, 9, 43, 48, 54, 76, 85, 191, 218, 280, 289, 290, 325, 329, 332, 343, 348 Cholinesterase Inhibitors, 289, 332 Chorea, 41, 228, 237, 280, 282, 290 Choreatic Disorders, 290 Chorioretinitis, 290, 345 Choroid, 290, 345 Chromans, 46, 290 Chromatin, 281, 290, 320 Chromosomal, 69, 277, 290 Chromosome, 25, 290, 319, 347 Chronic Disease, 290, 292 Chronic Obstructive Pulmonary Disease, 104, 290 Chronic renal, 290, 337 Ciliary, 27, 68, 290, 325 Circadian, 68, 220, 227, 290 Circadian Rhythm, 220, 227, 290 CIS, 290, 345 Cisplatin, 4, 232, 290 Clamp, 12, 47, 290 Clear cell carcinoma, 290, 297 Clinical Medicine, 291, 338 Clinical trial, 5, 51, 105, 253, 291, 300, 340, 342 Clonic, 284, 291 Cloning, 68, 69, 78, 83, 118, 167, 205, 284, 291 Clozapine, 18, 64, 156, 169, 209, 291 Coca, 291 Cochlea, 152, 232, 291, 316 Cochlear, 231, 291, 359 Codeine, 189, 191, 222, 291, 330 Coenzyme, 281, 291 Cofactor, 134, 291, 340, 355 Cognition, 15, 18, 28, 32, 99, 109, 126, 199, 201, 213, 216, 291, 328 Cohort Studies, 291, 303 Colitis, 291, 317 Collagen, 238, 291, 292, 306, 336, 339 Collagen disease, 238, 292 Colloidal, 292, 352
367
Colon, 256, 291, 292, 317 Colostomy, 191, 222, 292 Combination Therapy, 201, 292 Combinatorial, 181, 199, 292 Compacta, 10, 12, 65, 67, 144, 155, 193, 225, 292 Complement, 9, 51, 52, 54, 278, 292, 293, 309, 347 Complementary and alternative medicine, 147, 172, 292 Complementary medicine, 147, 292 Complete remission, 205, 293, 344 Complete response, 293 Compliance, 207, 293 Compulsions, 293, 329 Computational Biology, 253, 255, 293 Computed tomography, 50, 142, 207, 293 Computerized axial tomography, 293 Computerized tomography, 293 Conception, 293, 306, 309 Concomitant, 55, 293 Cones, 42, 293, 345 Confusion, 228, 293, 298, 328, 358 Congestion, 280, 293 Conjugated, 293, 326 Conjunctiva, 293, 357 Connective Tissue, 281, 285, 291, 292, 293, 297, 306, 308, 320, 354 Connexins, 293, 308 Consciousness, 158, 278, 294, 296, 298, 341 Constipation, 191, 222, 280, 294, 307, 317, 348 Constitutional, 294, 345 Constriction, 294, 317, 358 Constriction, Pathologic, 294, 358 Contraindications, ii, 211, 294 Contralateral, 294, 322, 330, 343 Convulsions, 279, 294, 328 Coordination, 100, 184, 229, 237, 288, 294 Cor, 38, 294, 336, 339 Corneum, 210, 294, 303 Coronary, 135, 211, 278, 294, 326 Coronary heart disease, 211, 294 Coronary Thrombosis, 294, 326 Corpus, 66, 88, 187, 294, 295, 309, 320, 327, 333, 339, 354, 360 Corpus Luteum, 294, 320, 339 Corpus Striatum, 66, 88, 187, 295, 309, 327 Cortex, 15, 18, 20, 26, 28, 29, 37, 40, 43, 45, 46, 53, 57, 63, 66, 72, 80, 123, 126, 141, 144, 148, 150, 152, 153, 157, 159, 160, 162, 173, 174, 295, 303, 323, 338
Cortical, 30, 43, 46, 53, 59, 63, 92, 93, 149, 242, 295, 305, 336, 338, 347, 354 Corticosteroids, 295, 310, 323 Coumarin, 295 Cranial, 282, 288, 295, 304, 311, 330, 332, 334, 357, 358, 359 Craniocerebral Trauma, 283, 295, 311, 354 Creatinine, 4, 137, 238, 295 Creatinine clearance, 4, 137, 238, 295 Cribriform, 295, 330 Crossing-over, 295, 343 Cross-Sectional Studies, 295, 303 Cues, 7, 151, 295 Cultured cells, 34, 295 Curare, 295, 325 Curative, 295, 329, 354 Cyclic, 27, 31, 80, 81, 87, 100, 128, 274, 286, 295, 307, 311, 329, 335, 340, 347 Cyclin, 69, 204, 295 Cyproheptadine, 71, 295 Cysteine, 24, 64, 296, 352 Cystine, 296 Cytokine, 100, 102, 296 Cytoplasm, 281, 287, 296, 310, 320, 346, 353 Cytoskeleton, 73, 296 Cytotoxic, 296, 349 Cytotoxicity, 103, 128, 149, 160, 276, 290, 296 D Dark Adaptation, 20, 42, 50, 296 De novo, 157, 296 Deamination, 296, 358 Decarboxylation, 296, 312 Decidua, 296, 336 Degenerative, 7, 131, 176, 193, 237, 296, 325 Deletion, 281, 296, 309 Delirium, 280, 296 Delusions, 228, 296, 341 Dementia, 118, 193, 220, 235, 238, 280, 296 Dendrites, 26, 27, 39, 43, 63, 296, 297, 328, 330 Dendritic, 27, 63, 69, 88, 297, 321 Dental Caries, 297, 307 Dentate Gyrus, 297, 312 Depolarization, 29, 190, 297, 349 Deprenyl, 145, 297, 347 Depressive Disorder, 216, 220, 297, 319 Deprivation, 86, 297 Dermis, 210, 297, 345, 352, 356 DES, 141, 142, 278, 297
368
Dopamine
Desensitization, 57, 61, 65, 72, 115, 132, 297 Deuterium, 173, 297, 313 Developed Countries, 211, 297 Dextroamphetamine, 277, 297, 322, 323 Diabetes Mellitus, 297, 312, 316 Diagnostic procedure, 179, 243, 297 Diaphragm, 237, 297 Diarrhea, 196, 223, 298, 307, 317, 321 Diastolic, 298, 313 Diffusion, 29, 31, 50, 190, 227, 283, 298 Digestion, 276, 283, 285, 298, 308, 316, 319, 333, 351, 358 Dihydrotestosterone, 298, 343 Dilatation, Pathologic, 298, 358 Dilation, 285, 298, 358, 359 Dimerization, 56, 298 Dimethyl, 188, 214, 298, 320 Discrete, 48, 163, 298, 354 Discrimination, 73, 298 Disease Progression, 101, 207, 298 Disease Vectors, 298, 316 Disinfectant, 298, 304 Disorientation, 293, 296, 298 Disparity, 123, 298 Dissociation, 151, 275, 298 Distal, 298, 301, 308, 338, 340, 345 Disulfiram, 136, 298 DNA Topoisomerase, 299, 309 Dobutamine, 120, 141, 299 Dominance, 299, 318 Domperidone, 196, 299 Dopa, 16, 57, 120, 173, 182, 225, 283, 286, 299, 318 Dopa Decarboxylase, 283, 286, 299 Dopamine Antagonists, 18, 36, 55, 67, 154, 235, 238, 299 Dorsal, 10, 107, 299, 303, 324, 337, 348 Dorsum, 299, 308 Dosage Forms, 188, 189, 203, 213, 219, 299 Dose-dependent, 20, 300 Dosimetry, 50, 104, 300 Double-blind, 4, 105, 300 Drinking Behavior, 30, 300 Drip, 221, 300 Drive, ii, vi, 28, 30, 55, 139, 145, 181, 200, 300, 318 Drug Design, 16, 300 Drug Interactions, 4, 215, 246, 300 Drug Tolerance, 300, 355 Drug Toxicity, 287, 300 Duct, 287, 300, 305, 346, 352
Dumping Syndrome, 295, 300 Duodenum, 283, 300, 308, 325, 328, 332, 333, 351 Dyes, 277, 300, 307 Dynorphins, 300, 330 Dyskinesia, 19, 41, 119, 169, 220, 229, 280, 300 Dyslexia, 126, 300 Dysmenorrhea, 301, 326 Dysphonia, 237, 301 Dysphoria, 99, 181, 301 Dysphoric, 297, 301 Dysplasia, 257, 301 Dystonia, 52, 66, 108, 237, 280, 301 Dystrophy, 257, 301 E Eating Disorders, 96, 182, 213, 215, 301 Edema, 132, 301 Effector, 27, 67, 273, 292, 301, 335 Efferent, 226, 301, 316, 325, 348 Efficacy, 15, 16, 18, 20, 33, 41, 77, 102, 105, 144, 182, 216, 300, 301, 320, 357 Eicosanoids, 236, 301 Ejaculation, 181, 301, 347 Elastin, 292, 301 Elective, 4, 87, 88, 163, 301 Electroacupuncture, 148, 301 Electrochemistry, 29, 30, 301 Electrode, 29, 30, 105, 301 Electrolyte, 275, 296, 301, 323, 337, 349 Electrons, 280, 283, 301, 317, 331, 342 Electroplating, 287, 301 Electroporation, 210, 301 Electroretinogram, 42, 96, 302 Embolus, 302, 315 Embryo, 85, 284, 287, 302, 315, 337 Emesis, 181, 199, 238, 280, 302 Emetic, 196, 280, 302 Emphysema, 290, 302 Empirical, 18, 302 Emulsion, 282, 302, 306 Encephalitis, 237, 302 Encephalitis, Viral, 302 Endocrine System, 302, 327 Endocytosis, 85, 115, 302 Endorphin, 57, 302 Endothelial cell, 284, 302, 312, 354 Endothelium, 302, 303, 329 Endothelium-derived, 303, 329 Endotoxin, 303, 329, 357 End-stage renal, 290, 303, 337 Energetic, 11, 303
369
Enhancer, 198, 303 Enkephalin, 38, 57, 74, 303, 339 Entorhinal Cortex, 303, 312 Environmental Exposure, 193, 303, 330 Environmental Health, 252, 254, 303 Enzymatic, 53, 190, 286, 292, 297, 303, 312, 345 Enzyme Inhibitors, 206, 214, 303 Ephedrine, 188, 303 Epidemic, 32, 303, 350 Epidemiologic Studies, 193, 303 Epidermis, 294, 297, 303 Epinephrine, 90, 97, 105, 192, 214, 238, 274, 299, 303, 328, 329, 357 Epithalamus, 303, 319 Epithelial, 98, 106, 117, 136, 206, 274, 283, 296, 303, 304, 323 Epithelial Cells, 98, 106, 117, 136, 274, 304, 323 Erectile, 189, 203, 206, 213, 219, 304, 333 Erection, 304 Ergot, 130, 222, 275, 285, 304, 346 Ergot Alkaloids, 222, 304 Erythrocytes, 196, 278, 284, 285, 304, 347 Escalation, 22, 304 Esophagus, 304, 308, 320, 333, 334, 351 Essential Tremor, 257, 304 Estradiol, 35, 304 Estriol, 238, 304 Estrogen, 33, 77, 174, 304, 339 Ethanol, 15, 21, 30, 31, 47, 49, 85, 160, 176, 177, 275, 304, 306 Ether, 216, 304 Ethmoid, 304, 330 Eukaryotic Cells, 304, 315, 357 Euphoria, 223, 304 Evacuation, 294, 304, 308 Evoke, 305, 351 Excitability, 12, 18, 26, 43, 47, 59, 305, 326 Excitation, 288, 289, 305, 306, 328 Excitatory, 6, 12, 29, 37, 42, 43, 54, 63, 72, 73, 84, 87, 175, 190, 232, 236, 277, 305, 310, 328 Excitatory Amino Acids, 73, 236, 305, 328 Excitatory Postsynaptic Potentials, 73, 305 Excrete, 305, 344 Exhaustion, 228, 278, 305, 318 Exocrine, 65, 289, 305, 332 Exocytosis, 75, 148, 305, 353 Exogenous, 186, 275, 299, 302, 305, 325, 357 Exon, 4, 107, 109, 276, 305
Expiration, 305, 344 Expiratory, 186, 305 Exploratory Behavior, 7, 60, 305 Extracellular Matrix, 293, 305, 306 Extracellular Space, 15, 31, 305, 323 Extrapyramidal, 18, 51, 131, 187, 199, 209, 215, 216, 275, 276, 280, 299, 305 F Family Planning, 253, 305 Fat, 204, 274, 281, 285, 286, 294, 302, 305, 319, 331, 337 Fatigue, 4, 228, 305, 311 Fatty acids, 150, 301, 305, 339 Fecal Incontinence, 190, 191, 222, 306, 315 Feces, 191, 222, 294, 306, 351, 358 Femoral, 286, 306 Femoral Artery, 286, 306 Fenfluramine, 36, 306 Fermentation, 275, 306 Fetal Alcohol Syndrome, 21, 306 Fetus, 32, 188, 306, 336, 338, 358 Fibroblasts, 23, 306 Fibrosis, 108, 257, 276, 306, 346 Fissure, 297, 306, 338 Fixation, 306, 347 Flatus, 306, 308 Flow Cytometry, 76, 306 Fludrocortisone, 237, 307 Fluorescence, 100, 127, 183, 306, 307 Fluorescent Dyes, 306, 307 Fluorine, 178, 307 Fluoxetine, 36, 202, 307 Flushing, 299, 307 Folate, 150, 307 Fold, 19, 43, 61, 306, 307 Folic Acid, 307 Forearm, 284, 307 Forskolin, 70, 307 Fossa, 288, 307 Fractionation, 307, 353 Free Radicals, 19, 279, 298, 307 Frontal Lobe, 228, 279, 288, 307, 325, 338 Functional Disorders, 54, 213, 307 Fungus, 304, 307, 346 Fusaric Acid, 226, 308 G Gait, 166, 288, 308 Gallate, 111, 156, 157, 161, 308 Gallbladder, 273, 289, 308 Ganglia, 7, 23, 34, 35, 48, 52, 59, 72, 77, 80, 87, 100, 177, 216, 273, 280, 283, 308, 319, 327, 329, 332, 334, 342, 352
370
Dopamine
Ganglion, 20, 72, 308, 331, 359 Gap Junctions, 79, 294, 308, 353 Gas, 191, 222, 277, 286, 298, 306, 307, 308, 313, 317, 321, 329, 330, 344, 352, 359 Gastrectomy, 295, 308 Gastric, 3, 4, 211, 212, 238, 299, 308, 312, 325, 333 Gastric Emptying, 4, 308 Gastric Juices, 308, 333 Gastrin, 308, 312 Gastroesophageal Reflux, 4, 308 Gastrointestinal tract, 216, 290, 304, 308, 318, 348 Gastroparesis, 4, 238, 308 Gene Deletion, 14, 308 Gene Expression, 14, 17, 34, 45, 50, 74, 98, 137, 162, 178, 183, 258, 309 Gene Expression Profiling, 14, 309 Gene Therapy, 23, 33, 309 Genetic Engineering, 284, 291, 309 Genetic Markers, 37, 309 Genistein, 155, 309 Genotype, 98, 112, 309, 335 Geriatric, 118, 187, 309 Germ Cells, 309, 321, 330, 331, 350, 354 Gestation, 58, 309, 336 Gestation period, 58, 309 Ginseng, 154, 169, 171, 309 Gland, 71, 76, 274, 309, 320, 332, 336, 340, 346, 347, 351, 352, 355 Globus Pallidus, 8, 52, 178, 283, 295, 309, 342 Glomerular, 236, 309, 317, 344 Glomerular Filtration Rate, 236, 309 Glomeruli, 310, 330 Glomerulus, 309, 310 Glottis, 237, 310 Glucocorticoid, 38, 75, 89, 310, 323 Glucose, 54, 238, 257, 281, 284, 297, 310, 312, 316, 342 Glucuronic Acid, 310, 312 Glutamic Acid, 226, 277, 307, 310, 328, 339 Glycine, 277, 310, 328 Glycoprotein, 178, 310, 325, 354, 357 Gonadal, 310, 351 Gonadotropin, 162, 176, 310 Gout, 310, 314, 326 Governing Board, 310, 338 Graft, 37, 310, 315 Grafting, 4, 191, 222, 310, 315 Gram-negative, 310, 355 Granule, 113, 297, 310, 346
Granulocytes, 310, 318, 349, 360 Growth factors, 212, 310, 323 Guanine, 14, 34, 174, 311 Guanosine Triphosphate, 23, 311 Guanylate Cyclase, 311, 329 Gyrus Cinguli, 279, 311, 319 H Habituation, 60, 79, 311 Haematemesis, 302, 311 Hair follicles, 297, 311 Half-Life, 221, 311 Hallucinogen, 311, 334 Haloperidol, 13, 63, 64, 107, 134, 164, 175, 311, 350 Handedness, 128, 311 Handicap, 100, 311 Haptens, 188, 275, 311 Headache, 130, 311, 338, 348 Headache Disorders, 311 Heart failure, 114, 303, 311 Hemiplegia, 282, 311 Hemodynamics, 90, 236, 311 Hemoglobin, 238, 278, 284, 304, 311, 312 Hemoglobinopathies, 309, 312 Hemoglobinuria, 257, 312 Hemorrhage, 295, 311, 312, 351 Hemostasis, 312, 348 Heparin, 210, 211, 312 Heparin-binding, 211, 312 Hereditary, 237, 290, 310, 312, 325, 327, 336, 345 Heredity, 308, 309, 312 Heterodimer, 56, 285, 312 Heterogeneity, 275, 312 Hippocampus, 62, 153, 159, 174, 297, 312, 319, 348, 352 Histamine, 238, 278, 280, 295, 312, 320 Histidine, 312 Homeostasis, 13, 25, 184, 226, 312, 332, 349 Homologous, 115, 212, 276, 293, 295, 309, 312, 328, 347, 353 Homozygotes, 4, 299, 312 Hormonal, 282, 312 Humoral, 236, 313 Humour, 313 Hybrid, 89, 125, 313, 346 Hybridomas, 302, 313 Hydrogen, 19, 24, 93, 116, 198, 208, 209, 226, 227, 273, 275, 277, 283, 286, 297, 313, 319, 324, 331, 334, 340, 352 Hydrogen Bonding, 24, 313 Hydrogen Peroxide, 19, 93, 313, 319, 352
371
Hydrolysis, 59, 273, 290, 313, 335, 337, 340 Hydrophilic, 24, 313 Hydrophobic, 98, 313 Hydroxylation, 313, 357 Hydroxylysine, 292, 313 Hydroxyproline, 292, 313 Hypericum, 147, 157, 158, 163, 171, 313 Hypersecretion, 83, 313 Hypersensitivity, 276, 297, 313, 318, 345, 347 Hypertension, 25, 92, 108, 110, 181, 199, 211, 215, 225, 226, 230, 311, 313, 339 Hyperthyroidism, 313, 339 Hypertrophy, 213, 294, 314, 357 Hyperuricaemia, 196, 314 Hypokinesia, 314, 332 Hypotension, 116, 280, 294, 299, 314, 328 Hypothalamic, 38, 116, 124, 135, 141, 166, 176, 180, 193, 197, 314 Hypothalamus, 35, 38, 84, 282, 303, 314, 319, 328, 336, 339, 348, 354 Hypoxanthine, 34, 314 Hypoxic, 90, 114, 314 I Idiopathic, 54, 118, 137, 218, 237, 314 Ileum, 74, 314, 328 Ileus, 238, 314 Immune response, 279, 311, 314, 347, 352, 359, 360 Immune system, 74, 212, 283, 314, 318, 358, 360 Immunity, 72, 314 Immunization, 314, 315, 347 Immunoblotting, 35, 314 Immunochemistry, 17, 314 Immunodeficiency, 74, 256, 314 Immunohistochemistry, 22, 37, 314 Immunology, 123, 136, 275, 307, 314 Immunosuppressant, 276, 314 Immunosuppressive, 310, 314, 315 Immunotherapy, 283, 297, 314 Immunotoxin, 150, 315 Impairment, 25, 81, 125, 165, 199, 231, 281, 283, 296, 300, 301, 315, 322, 341 Implantation, 96, 117, 293, 315 Impotence, 304, 315 Impulsive Behavior, 20, 315 In situ, 13, 35, 82, 232, 315 In Situ Hybridization, 13, 35, 82, 315 In vivo, 5, 12, 14, 15, 29, 32, 38, 39, 43, 45, 47, 49, 50, 51, 54, 55, 61, 62, 67, 68, 75, 79, 86, 98, 109, 117, 118, 134, 142, 143,
149, 176, 178, 182, 186, 207, 213, 215, 217, 235, 309, 312, 315, 323, 355 Incision, 315, 317 Incompetence, 308, 315 Incontinence, 181, 191, 213, 222, 303, 315 Incubation, 166, 315 Induction, 11, 80, 84, 87, 125, 158, 280, 315, 318, 339 Infancy, 10, 16, 140, 315, 335 Infarction, 4, 288, 315 Infection, 58, 76, 206, 281, 282, 283, 289, 290, 296, 302, 314, 315, 320, 333, 345, 351, 360 Infertility, 285, 315 Inflammation, 167, 279, 281, 285, 290, 291, 302, 306, 315, 318, 328, 337, 345 Infusion, 41, 76, 82, 122, 136, 154, 158, 316 Ingestion, 26, 49, 316, 332, 337 Inhalation, 275, 316, 317, 337 Initiation, 27, 34, 45, 193, 225, 316, 356 Inner ear, 232, 316 Innervation, 27, 29, 31, 43, 61, 76, 150, 232, 316 Inorganic, 193, 290, 316, 325, 335 Inositol, 78, 316, 322, 347 Inotropic, 277, 299, 316, 323 Insecticides, 17, 163, 164, 193, 316, 334, 360 Insight, 6, 8, 22, 44, 54, 58, 316 Insomnia, 316, 338, 348 Insulin, 316, 357 Intensive Care, 120, 123, 129, 316 Interindividual, 13, 316 Intermittent, 23, 31, 45, 228, 316 Internal Capsule, 279, 295, 316 Interneurons, 18, 316 Interstitial, 305, 316, 344 Intestinal, 3, 4, 218, 286, 289, 316, 321, 358 Intestinal Mucosa, 289, 316, 358 Intestine, 285, 316, 334, 343, 349 Intoxication, 296, 316, 360 Intramuscular, 317, 332 Intraocular, 61, 307, 317 Intraocular pressure, 307, 317 Intravenous, 4, 81, 221, 316, 317, 332 Intrinsic, 28, 236, 275, 317 Introns, 317, 341 Intubation, 4, 287, 317 Inulin, 310, 317 Invasive, 15, 314, 317, 320 Invertebrates, 190, 298, 317 Involuntary, 23, 52, 201, 229, 237, 283, 290, 304, 306, 317, 326, 344, 348, 350, 355
372
Dopamine
Iodine, 182, 317 Ion Channels, 24, 27, 61, 73, 281, 317, 343, 353 Ionizing, 303, 317, 321 Ions, 24, 119, 283, 286, 298, 301, 313, 317, 324, 338 Iris, 317, 325 Irritable Bowel Syndrome, 181, 307, 317 Ischemia, 278, 282, 317, 328 Isoflurane, 103, 317 K Kainate, 144, 318 Kb, 252, 318 Ketamine, 120, 318, 334 Kidney Disease, 114, 252, 257, 318 Kidney stone, 238, 318, 344, 358 Kinetic, 120, 214, 317, 318 L Labile, 292, 318 Labyrinth, 291, 316, 318, 347, 359 Lactation, 318, 339 Larynx, 310, 318, 358, 360 Lassitude, 4, 318 Laterality, 38, 318 Lesion, 7, 20, 23, 30, 79, 89, 144, 318, 319, 353, 357 Leucocyte, 318, 320 Leukemia, 77, 256, 309, 318 Leukotrienes, 281, 301, 318 Levo, 299, 318 Levodopa, 39, 41, 80, 98, 105, 117, 143, 165, 169, 170, 201, 203, 237, 283, 286, 299, 318, 347 Libido, 203, 318 Lice, 319 Lidocaine, 235, 319 Life cycle, 284, 319 Ligament, 319, 340 Limbic, 11, 22, 30, 53, 57, 59, 63, 65, 80, 180, 197, 199, 201, 205, 216, 277, 311, 319, 338 Limbic System, 80, 199, 216, 277, 311, 319, 338 Linkage, 10, 59, 110, 121, 126, 183, 309, 319 Linkage Disequilibrium, 126, 319 Lipid, 19, 124, 125, 162, 289, 316, 319, 331 Lipid Peroxidation, 19, 124, 319, 331 Lipophilic, 50, 319 Lipopolysaccharide, 144, 164, 165, 310, 319 Lithium, 153, 280, 319
Liver, 196, 216, 273, 281, 283, 302, 306, 307, 308, 310, 312, 319, 329, 358 Lobe, 279, 288, 319, 339 Localization, 56, 63, 68, 69, 71, 80, 82, 83, 122, 199, 201, 314, 319 Localized, 15, 23, 185, 273, 297, 306, 311, 315, 319, 336, 357 Locomotion, 7, 13, 15, 18, 22, 56, 319, 320, 336 Locomotor, 5, 7, 21, 22, 37, 41, 56, 59, 60, 65, 77, 82, 138, 145, 174, 177, 213, 320 Longitudinal study, 10, 107, 320 Long-Term Potentiation, 62, 320 Loop, 66, 135, 320 Loperamide, 191, 222, 320 Lower Esophageal Sphincter, 4, 308, 320 Loxapine, 76, 104, 320 Lupus, 292, 320 Lutein Cells, 320, 339 Lymph, 289, 302, 313, 320 Lymph node, 289, 320 Lymphatic, 302, 315, 320, 337 Lymphoblasts, 14, 320 Lymphocytes, 65, 123, 131, 136, 163, 279, 313, 314, 318, 320, 360 Lymphoid, 279, 295, 318, 320 Lymphoma, 256, 320 M Macroglia, 320, 323 Magnetic Resonance Imaging, 39, 320 Malabsorption, 257, 321, 348 Malabsorption syndrome, 321, 348 Malaise, 301, 321 Malformation, 114, 321 Malignant, 121, 223, 256, 274, 279, 321 Malignant tumor, 274, 321 Malnutrition, 236, 282, 321, 326 Mania, 198, 220, 321 Manic, 280, 284, 319, 321, 341 Manic-depressive psychosis, 321, 341 Manifest, 28, 118, 187, 196, 311, 321 Man-made, 287, 321 Mastication, 321, 357 Meatus, 321, 358 Medial, 45, 46, 57, 84, 144, 153, 304, 309, 311, 321, 330, 348 Mediate, 28, 37, 45, 46, 49, 73, 115, 167, 287, 299, 321 Mediator, 49, 69, 180, 197, 289, 299, 321, 348 Medicament, 221, 321 MEDLINE, 253, 255, 257, 321
373
Medullary, 321, 342 Meiosis, 321, 353 Melanin, 10, 187, 317, 321, 335, 357 Melanocytes, 321, 322 Melanoma, 256, 322 Membrane Glycoproteins, 322 Memory, 7, 8, 16, 18, 30, 33, 80, 115, 144, 199, 212, 216, 278, 296, 320, 322 Meninges, 288, 295, 322 Menopause, 322, 339 Menstrual Cycle, 322, 338, 339 Mental deficiency, 306, 322 Mental Disorders, 111, 314, 322, 341 Mental Health, iv, 5, 142, 252, 254, 322, 341 Mental Retardation, 32, 141, 258, 322 Menthol, 155, 322 Mercury, 193, 306, 322 Mesencephalic, 37, 39, 64, 79, 82, 84, 90, 128, 156, 157, 165, 174, 322, 343 Metabolite, 37, 84, 188, 235, 298, 304, 322, 338 Metabotropic, 12, 322 Metastasis, 287, 322 Metastatic, 116, 322 Methamphetamine, 8, 9, 11, 21, 22, 40, 55, 94, 116, 122, 123, 177, 188, 189, 322 Methylphenidate, 11, 15, 32, 33, 41, 97, 103, 124, 323 Methyltransferase, 98, 99, 120, 214, 323 Metoclopramide, 4, 77, 246, 323 Microbe, 323, 356 Microbiology, 274, 282, 323 Microdialysis, 5, 31, 39, 43, 45, 49, 58, 176, 323 Microglia, 144, 151, 164, 281, 323, 324 Microorganism, 291, 323, 333, 360 Microscopy, 6, 61, 127, 323 Middle Cerebral Artery, 157, 323 Migration, 37, 160, 212, 323 Milrinone, 103, 141, 323 Mineralocorticoid, 307, 323 Mitochondria, 70, 163, 323 Mitosis, 281, 323 Mobility, 203, 324 Mobilization, 78, 324 Modeling, 50, 125, 300, 324 Modification, 29, 50, 53, 159, 182, 309, 324 Modulator, 72, 153, 213, 236, 324 Molecular Probes, 302, 324 Molecular Structure, 324, 357 Mollusca, 76, 324
Monitor, 15, 29, 137, 295, 324, 329 Monoamine, 8, 9, 33, 40, 62, 63, 119, 120, 140, 180, 181, 182, 185, 188, 194, 195, 197, 199, 205, 207, 211, 214, 215, 216, 217, 224, 232, 277, 297, 324, 347 Monoclonal, 76, 188, 313, 314, 324 Monoclonal antibodies, 188, 314, 324 Mononuclear, 324, 357 Monophosphate, 128, 324 Mood Disorders, 153, 203, 220, 324 Morphine, 15, 68, 75, 81, 140, 175, 189, 191, 222, 280, 285, 291, 324, 327, 330 Morphogenesis, 306, 324 Morphological, 56, 302, 308, 321, 324 Morphology, 44, 68, 325 Motilin, 238, 325 Motility, 3, 4, 70, 191, 198, 213, 216, 222, 238, 307, 325, 348 Motion Sickness, 325, 327 Motor Activity, 18, 48, 294, 325 Motor Cortex, 143, 155, 164, 325, 343 Motor nerve, 325, 330 Motor Skills, 229, 325 Mucinous, 308, 325 Mucolytic, 206, 325 Mucosa, 320, 325, 327, 339 Mucus, 27, 206, 325 Muscarinic Agonists, 19, 325 Muscarinic Antagonists, 19, 325 Muscle Contraction, 52, 325 Muscle Fibers, 325, 326 Muscle relaxant, 223, 235, 325 Muscle tension, 325 Muscular Atrophy, 257, 326 Mutagenesis, 24, 61, 326 Mutagenic, 276, 326 Mutagens, 326 Mutilation, 228, 326 Myocardial infarction, 4, 280, 294, 299, 326, 339 Myocardium, 278, 323, 326 Myoclonus, 66, 237, 326 Myoglobin, 238, 326 Myopia, 86, 326, 327, 344 Myosin, 325, 326 Myotonic Dystrophy, 257, 326 N Naloxone, 57, 326 Naltrexone, 30, 326 Naproxen, 194, 326 Narcolepsy, 187, 297, 303, 323, 326 Narcosis, 326
374
Dopamine
Narcotic, 228, 235, 273, 324, 326 Nasal Cavity, 327, 360 Nasal Mucosa, 206, 327 Natriuresis, 26, 327 Nausea, 4, 196, 238, 279, 280, 299, 308, 327, 332, 338, 358 Nearsightedness, 326, 327 Nebramycin, 327, 355 Necrosis, 280, 288, 315, 326, 327, 348 Neonatal, 20, 30, 37, 92, 327 Neoplasia, 256, 327 Neostriatum, 43, 77, 84, 287, 295, 327, 342 Nephron, 110, 310, 327 Nephropathy, 137, 318, 327 Nerve Endings, 327, 353 Nerve Fibers, 71, 327 Nerve Growth Factor, 83, 87, 158, 327, 328 Neuroblastoma, 19, 93, 118, 128, 136, 149, 156, 163, 327 Neurodegenerative Diseases, 35, 181, 283, 327 Neuroendocrine, 60, 82, 216, 233, 327 Neuroleptic, 42, 51, 67, 89, 112, 121, 209, 220, 238, 275, 280, 291, 328 Neurologic, 208, 209, 328 Neuromuscular, 273, 328 Neuromuscular Junction, 273, 328 Neuronal Plasticity, 77, 85, 328 Neurons, 5, 10, 12, 13, 15, 17, 18, 21, 23, 26, 27, 28, 29, 30, 31, 33, 34, 35, 37, 38, 39, 42, 43, 45, 47, 48, 49, 52, 57, 58, 59, 61, 62, 64, 65, 67, 68, 70, 72, 74, 75, 76, 77, 78, 79, 81, 82, 84, 85, 87, 88, 89, 90, 91, 93, 97, 99, 113, 117, 118, 119, 126, 138, 141, 142, 143, 144, 149, 150, 151, 153, 157, 158, 159, 161, 162, 164, 165, 166, 167, 175, 176, 181, 185, 190, 192, 193, 207, 212, 217, 219, 225, 229, 234, 242, 277, 288, 291, 296, 297, 305, 308, 316, 318, 325, 327, 328, 329, 330, 332, 343, 345, 352, 353, 359 Neuropeptide, 38, 71, 82, 328 Neuropharmacology, 7, 21, 29, 30, 108, 162, 195, 328 Neurophysiology, 55, 92, 94, 125, 157, 297, 328 Neuroprotective Agents, 131, 328 Neuropsychological Tests, 66, 328 Neuroretinitis, 328, 345 Neurotensin, 63, 67, 76, 77, 88, 328 Neurotoxic, 71, 87, 217, 242, 273, 328
Neurotoxicity, 10, 53, 87, 90, 126, 144, 156, 164, 165, 176, 177, 218, 232, 328 Neurotoxin, 37, 84, 328 Neurotrophin 3, 85, 328 Niacin, 329, 357 Nicotine, 46, 94, 132, 154, 160, 182, 191, 218, 329, 343 Night Blindness, 329, 345 Nitric Oxide, 19, 49, 84, 87, 142, 149, 191, 219, 222, 329 Nitric-Oxide Synthase, 149, 329 Nitrogen, 23, 227, 276, 277, 306, 329, 331, 357 Nuclei, 10, 46, 70, 216, 277, 301, 303, 309, 317, 321, 323, 329, 331, 332, 336, 340, 348, 359 Nucleic acid, 190, 314, 315, 326, 329 O Obsessive-Compulsive Disorder, 44, 182, 213, 329 Obstetrics, 101, 304, 330 Oculi, 284, 330 Oculomotor, 322, 330 Office Visits, 224, 330 Ointments, 300, 330 Olfaction, 330 Olfactory Bulb, 74, 160, 175, 330, 360 Olfactory Nerve, 330 Oncogene, 256, 330 On-line, 214, 271, 330 Oocytes, 46, 65, 78, 161, 330 Opiate, 30, 82, 176, 177, 186, 228, 303, 324, 326, 330 Opioid Peptides, 57, 300, 330 Opium, 324, 330 Opsin, 330, 345 Optic Chiasm, 314, 330, 331 Optic Nerve, 328, 330, 345 Orbicularis, 284, 331 Orbit, 331 Orbital, 150, 331 Organ Culture, 55, 331 Organic Chemicals, 193, 331 Orgasm, 301, 331 Orthostatic, 101, 280, 331 Outpatient, 331 Ovary, 294, 304, 331, 337 Overdose, 125, 188, 331 Overweight, 145, 203, 204, 211, 262, 331 Ovum, 295, 296, 309, 319, 331, 339 Oxidation, 75, 87, 99, 128, 165, 273, 280, 296, 319, 331
375
Oxidative Stress, 13, 19, 53, 125, 143, 156, 331 Oxygen Consumption, 331, 344 Oxygenation, 157, 331 Oxygenator, 286, 331 P Pacemaker, 90, 331 Palliative, 196, 332, 354 Palsy, 96, 193, 237, 332, 350 Pancreas, 65, 90, 273, 316, 332 Pancreatic, 3, 91, 256, 289, 308, 332 Pancreatic cancer, 256, 332 Pancreatic Juice, 308, 332 Pancreatic Polypeptide, 91, 332 Panic, 168, 182, 332, 348 Panic Disorder, 332, 348 Paralysis, 273, 275, 295, 322, 332, 350 Parasitic, 280, 319, 332 Parasympathetic Nervous System, 332 Parasympathomimetics, 235, 332 Parenteral, 189, 219, 332 Paroxetine, 41, 333 Paroxysmal, 257, 278, 311, 333 Partial response, 205, 333 Particle, 321, 333, 356 Parturition, 330, 333, 339 Patch, 12, 47, 333, 356 Pathogen, 315, 333 Pathologic, 273, 281, 294, 313, 333 Pathologic Processes, 281, 333 Pathophysiology, 11, 26, 29, 39, 44, 52, 53, 63, 113, 128, 224, 234, 235, 333 Patient Education, 262, 266, 268, 271, 333 Pelvic, 333, 340 Penicillamine, 105, 333 Penicillin, 278, 333, 358 Penis, 301, 333 Pepsin, 333 Peptic, 238, 333 Peptic Ulcer, 238, 333 Peptide, 13, 45, 62, 68, 93, 98, 167, 206, 289, 330, 333, 337, 339, 340, 355 Perception, 12, 27, 178, 333, 346 Perch, 72, 333 Perennial, 313, 333 Perfusion, 58, 333 Pergolide, 81, 99, 237, 246, 333 Peripheral Nervous System, 311, 327, 328, 332, 334, 338, 352, 358 Peristalsis, 299, 334 Perivascular, 323, 334 Pernicious, 238, 334
Pernicious anemia, 238, 334 Peroxide, 116, 334 Personality Disorders, 183, 334 Pesticides, 13, 17, 316, 334 PH, 50, 73, 142, 207, 334 Phagocytosis, 323, 334 Pharmaceutical Preparations, 221, 304, 334, 339 Pharmaceutical Solutions, 300, 334 Pharmacodynamic, 17, 334 Pharmacokinetic, 17, 334 Pharmacologic, 61, 235, 238, 278, 311, 334, 356 Pharmacology, Clinical, 4, 334 Pharmacotherapy, 21, 99, 137, 195, 211, 334 Pharynx, 308, 327, 334, 358 Phencyclidine, 28, 31, 217, 334 Phenotype, 15, 31, 34, 60, 84, 136, 143, 158, 309, 335 Phenyl, 16, 19, 37, 39, 52, 65, 67, 84, 87, 90, 157, 182, 198, 199, 200, 201, 217, 218, 227, 335 Phenylalanine, 134, 335, 357 Phenylalanine Hydroxylase, 134, 335 Phenylketonurias, 335 Phenylpropanolamine, 188, 335 Phosphates, 238, 335 Phosphodiesterase, 55, 175, 277, 323, 335, 346 Phospholipases, 335, 349 Phospholipids, 305, 316, 335 Phosphorus, 285, 331, 335 Phosphorylated, 35, 85, 291, 335 Phosphorylates, 34, 335 Phosphorylation, 35, 55, 64, 70, 71, 72, 84, 86, 89, 115, 141, 204, 212, 335, 340 Photoreceptor, 20, 49, 56, 73, 335, 345 Phototherapy, 335, 346 Physical Therapy, 166, 335 Physicochemical, 314, 335 Physiologic, 275, 284, 299, 311, 314, 317, 322, 326, 336, 339, 343, 348, 353, 357 Pigment, 119, 283, 321, 322, 326, 336 Pilot study, 103, 336 Piperidines, 180, 199, 336 Pituitary Gland, 140, 307, 336, 339, 347 Pituitary-Adrenal System, 135, 166, 336 Placebo Effect, 135, 166, 336 Placenta, 98, 304, 336, 339 Plants, 273, 276, 281, 286, 289, 291, 309, 310, 313, 317, 325, 329, 336, 337, 346, 356
376
Dopamine
Plasma cells, 279, 336 Plasmids, 302, 336 Plasticity, 35, 75, 97, 124, 336 Platelet Activation, 336, 349 Platelet Aggregation, 278, 307, 329, 336, 355 Platelets, 64, 329, 336, 354, 355 Pleomorphic, 329, 336 Plexus, 61, 337 Pneumonia, 294, 337 Point Mutation, 36, 337 Poisoning, 280, 296, 300, 304, 316, 322, 327, 337 Pollen, 275, 337 Polycystic, 257, 337 Polymers, 283, 337, 340, 351 Polymorphism, 4, 20, 91, 92, 93, 94, 104, 107, 108, 111, 112, 120, 121, 129, 337 Polypeptide, 24, 277, 291, 325, 326, 332, 337, 339, 340, 358, 361 Polysaccharide, 189, 220, 279, 337 Polyunsaturated fat, 159, 165, 337, 355 Pons, 186, 285, 337, 345 Posterior, 278, 282, 288, 290, 299, 303, 316, 317, 331, 332, 337 Postherpetic Neuralgia, 276, 337 Postnatal, 18, 21, 160, 306, 337, 351 Postoperative, 4, 238, 337 Postsynaptic, 5, 12, 18, 19, 32, 43, 48, 58, 63, 71, 77, 80, 142, 152, 161, 176, 190, 337, 349, 353 Post-synaptic, 5, 44, 55, 202, 337, 353 Post-translational, 53, 337 Post-traumatic, 114, 311, 325, 337 Post-traumatic stress disorder, 114, 337 Potassium, 12, 60, 238, 275, 323, 337, 338 Potassium Channels, 12, 338 Potentiates, 192, 219, 338 Potentiating, 35, 338 Potentiation, 43, 133, 290, 320, 338, 349 Practicability, 338, 357 Practice Guidelines, 254, 338 Preclinical, 9, 216, 338 Precursor, 16, 84, 201, 278, 281, 285, 289, 299, 301, 303, 318, 329, 335, 338, 339, 357, 358 Premenstrual Syndrome, 203, 338 Prenatal, 21, 32, 48, 175, 302, 306, 338 Presynaptic, 5, 32, 43, 71, 118, 123, 153, 190, 217, 282, 327, 328, 338, 353 Presynaptic Terminals, 190, 282, 327, 338, 353
Prevalence, 12, 80, 115, 211, 338 Probe, 16, 29, 323, 338 Procaine, 275, 319, 338 Prodrug, 338 Progesterone, 35, 85, 339, 351 Progression, 15, 33, 52, 96, 97, 185, 224, 278, 339, 347 Projection, 13, 30, 47, 49, 316, 329, 330, 331, 338, 339, 343, 359 Prolactin, 81, 82, 83, 142, 176, 285, 299, 339 Proline, 292, 313, 339 Promoter, 13, 45, 86, 90, 109, 112, 120, 167, 211, 339 Pro-Opiomelanocortin, 86, 330, 339 Prophase, 330, 339, 353 Prophylaxis, 153, 222, 339 Propranolol, 237, 339 Propylene Glycol, 228, 339 Prospective study, 320, 339 Prostaglandin, 191, 222, 339, 355 Prostaglandins A, 339, 340 Prostate, 256, 340 Protease, 292, 340 Protective Agents, 207, 340 Protein C, 14, 116, 242, 277, 340, 358 Protein Conformation, 277, 340 Protein Isoforms, 276, 340 Protein S, 108, 110, 113, 119, 257, 258, 284, 340, 346 Proteins, 13, 14, 25, 27, 51, 53, 58, 61, 62, 106, 108, 119, 157, 190, 207, 210, 212, 215, 238, 276, 277, 279, 283, 284, 285, 287, 290, 292, 293, 302, 308, 312, 313, 324, 329, 333, 336, 337, 340, 342, 343, 348, 356, 359 Protein-Tyrosine Kinase, 309, 340 Proteolytic, 53, 285, 292, 340 Protocol, 26, 340 Protons, 313, 317, 340, 342 Proximal, 25, 45, 70, 298, 327, 338, 340, 348 Pruritus, 280, 341 Pseudogenes, 83, 341 Psychic, 318, 322, 341, 347 Psychoactive, 190, 217, 236, 341, 354, 360 Psychosis, 4, 8, 22, 56, 181, 199, 201, 222, 228, 280, 341 Psychosomatic, 148, 341 Psychotomimetic, 277, 297, 341 Psychotropic, 84, 341 Public Health, 6, 254, 341 Public Policy, 253, 341 Publishing, 63, 238, 341
377
Pulmonary, 186, 277, 284, 294, 318, 341, 344, 359 Pulmonary Artery, 284, 341, 359 Pulmonary hypertension, 294, 341 Pulse, 302, 324, 341 Punishment, 341, 345 Purifying, 53, 341 Putamen, 8, 14, 71, 155, 201, 205, 217, 279, 283, 295, 327, 342 Pyramidal Tracts, 305, 342 Q Quinones, 29, 342 Quinpirole, 155, 342 R Race, 188, 194, 213, 214, 299, 323, 342 Racemic, 188, 194, 213, 214, 299, 342 Raclopride, 11, 50, 54, 73, 155, 342 Radiation, 50, 53, 177, 278, 282, 303, 307, 317, 321, 342, 361 Radioactive, 182, 282, 311, 313, 315, 321, 324, 329, 342, 353, 357 Radiolabeled, 182, 184, 207, 284, 342 Radiopharmaceutical, 184, 342 Rage, 228, 342 Random Allocation, 342 Randomization, 39, 342 Randomized, 4, 105, 107, 123, 301, 342 Randomized clinical trial, 123, 342 Rape, 337, 342 Reabsorption, 25, 190, 236, 238, 342 Reaction Time, 21, 342 Reactive Oxygen Species, 116, 166, 343 Reagent, 62, 343 Reality Testing, 341, 343 Receptivity, 85, 141, 343 Receptors, Dopamine, 14, 343 Receptors, Muscarinic, 325, 343 Receptors, Neurotransmitter, 182, 343 Receptors, Serotonin, 343, 348 Recombinant, 61, 82, 86, 114, 131, 343, 359 Recombination, 31, 212, 309, 343 Recovery of Function, 39, 343 Rectum, 280, 285, 292, 306, 308, 315, 340, 343 Recur, 343, 346 Recurrence, 284, 290, 321, 343, 346 Red Nucleus, 282, 343, 359 Reductase, 34, 335, 343 Refer, 1, 184, 292, 306, 316, 319, 328, 341, 344, 356 Reflex, 160, 175, 228, 344, 357 Refraction, 326, 344, 350
Refractive Power, 326, 344 Refractory, 207, 216, 344 Regimen, 14, 51, 301, 334, 336, 344 Regurgitation, 308, 344 Relapse, 22, 45, 46, 47, 122, 344 Relaxant, 307, 344 Reliability, 210, 344 Remission, 284, 321, 343, 344 Remoxipride, 64, 344 Renal failure, 4, 236, 296, 344 Renal pelvis, 318, 344 Renal tubular, 122, 158, 344 Renin, 25, 77, 226, 236, 278, 344 Research Design, 40, 344 Research Support, 30, 43, 344 Resection, 191, 222, 344, 348 Respiration, 186, 216, 286, 289, 295, 324, 344 Respiratory System, 344, 358 Restless legs, 132, 345 Reticular, 80, 156, 345 Reticular Formation, 156, 345 Retina, 20, 42, 50, 55, 61, 70, 78, 81, 85, 88, 159, 290, 293, 326, 328, 330, 331, 345, 346, 360 Retinal, 42, 50, 55, 61, 65, 72, 73, 78, 86, 87, 101, 298, 330, 331, 345 Retinitis, 55, 228, 345 Retinitis Pigmentosa, 55, 228, 345 Retinoblastoma, 256, 345 Retinoid, 86, 345 Retinol, 345 Retraction, 73, 345 Retroviral vector, 309, 345 Reversal Learning, 73, 345 Rheumatoid, 292, 326, 345 Rheumatoid arthritis, 292, 326, 345 Rhinitis, 303, 345 Rhodopsin, 330, 345 Ribose, 274, 346 Ribosome, 346, 356 Rigidity, 193, 225, 229, 235, 237, 332, 336, 346 Risk factor, 10, 17, 26, 106, 210, 303, 339, 346 Risk patient, 137, 346 Rod, 20, 55, 290, 335, 346 Rodenticides, 334, 346 Rolipram, 175, 346 Rotenone, 149, 151, 152, 158, 162, 163, 164, 165, 346 Rye, 82, 304, 346
378
Dopamine
S Saliva, 346 Salivary, 71, 325, 332, 346 Saponin, 154, 346 Schizoid, 346, 360 Schizophrenia, Catatonic, 287, 346 Schizotypal Personality Disorder, 346, 360 Sclerosis, 257, 292, 346 Screening, 131, 181, 182, 190, 199, 207, 211, 212, 213, 291, 346 Seasonal Affective Disorder, 99, 346 Sebaceous, 297, 346 Sebaceous gland, 297, 346 Second Messenger Systems, 343, 347 Secretion, 3, 27, 71, 80, 82, 89, 91, 142, 213, 236, 285, 290, 312, 313, 318, 323, 325, 347, 358 Secretory, 60, 211, 347, 353 Sedative, 291, 347 Segregation, 343, 347 Seizures, 296, 333, 335, 347 Selegiline, 237, 347 Sella, 299, 336, 347 Sella Turcica, 299, 336, 347 Semen, 301, 340, 347 Semicircular canal, 316, 347 Seminal vesicles, 122, 347 Semisynthetic, 285, 347 Senile, 237, 238, 280, 347 Sensibility, 277, 347 Sensitization, 14, 22, 37, 43, 45, 56, 80, 102, 114, 133, 167, 177, 201, 347 Sensor, 173, 347 Sepsis, 135, 347 Septal, 201, 279, 319, 348 Septal Nuclei, 279, 319, 348 Septic, 105, 135, 281, 348 Sequencing, 183, 348, 353 Sequester, 192, 348, 353 Serotonin, 10, 24, 25, 36, 40, 41, 44, 48, 59, 63, 64, 65, 67, 69, 70, 76, 77, 83, 84, 86, 94, 98, 104, 105, 111, 123, 127, 132, 133, 137, 148, 163, 166, 176, 181, 182, 184, 185, 188, 190, 192, 195, 198, 199, 200, 201, 205, 208, 214, 215, 216, 217, 219, 224, 228, 230, 232, 235, 236, 238, 274, 280, 291, 295, 306, 307, 328, 333, 334, 343, 348, 357 Serotonin Agonists, 348 Serotonin Antagonists, 235, 348 Serotonin Uptake Inhibitors, 202, 348 Serum, 82, 278, 292, 310, 323, 348, 357
Sex Determination, 257, 348 Shivering, 185, 348 Shock, 105, 135, 145, 167, 169, 326, 348, 356 Short Bowel Syndrome, 238, 348 Sibutramine, 187, 188, 214, 228, 348 Signal Transduction, 27, 33, 51, 59, 213, 316, 349 Signs and Symptoms, 344, 349 Skeletal, 203, 213, 218, 290, 295, 349, 350 Skeleton, 273, 339, 349 Skull, 295, 331, 349, 354 Small intestine, 300, 313, 314, 316, 349 Smoking Cessation, 105, 285, 349 Smooth muscle, 276, 278, 304, 307, 312, 323, 324, 325, 349, 350, 352 Social Isolation, 191, 222, 346, 349 Social Problems, 9, 349 Sodium, 11, 24, 25, 76, 88, 106, 119, 226, 236, 238, 275, 310, 323, 326, 327, 342, 349, 352 Solitary Nucleus, 282, 349 Solvent, 304, 334, 339, 350 Soma, 350 Somatic, 224, 313, 319, 321, 323, 334, 338, 350, 358 Somnolence, 242, 350 Soybean Oil, 337, 350 Spasm, 282, 284, 322, 350 Spasmodic, 237, 350 Spastic, 317, 350 Specialist, 263, 298, 350 Specificity, 5, 10, 60, 93, 182, 194, 238, 275, 350 Spectrometer, 214, 350 Spectrum, 8, 15, 205, 323, 350 Sperm, 275, 290, 337, 350 Sphincter, 191, 222, 318, 350 Spinal cord, 281, 285, 288, 289, 291, 308, 311, 322, 327, 328, 332, 334, 342, 344, 350, 352 Spiperone, 86, 350 Splanchnic Circulation, 105, 350 Sporadic, 327, 345, 350 Stabilization, 120, 350 Startle Reaction, 154, 350 Stasis, 238, 350 Steel, 290, 351 Stem Cells, 37, 77, 91, 138, 142, 153, 166, 351 Stereotypy, 48, 80, 351 Steroid, 35, 351
379
Stimulus, 7, 36, 53, 99, 142, 212, 237, 300, 301, 305, 315, 316, 317, 341, 342, 344, 350, 351, 354 Stomach, 273, 304, 308, 313, 320, 327, 333, 334, 349, 351 Stool, 191, 222, 223, 292, 315, 317, 351 Stria, 32, 34, 348, 351 Stroke, 222, 226, 252, 286, 328, 351 Stroke Volume, 226, 286, 351 Stromal, 78, 351 Structure-Activity Relationship, 16, 50, 351 Stupor, 326, 327, 346, 351 Styrene, 232, 351 Subacute, 315, 351 Subarachnoid, 311, 351 Subclinical, 118, 315, 347, 351 Subcutaneous, 164, 210, 301, 332, 352 Subiculum, 312, 352 Subspecies, 350, 352 Substance P, 322, 347, 352 Substrate, 6, 21, 23, 24, 35, 65, 75, 77, 133, 303, 352 Sulfur, 331, 352 Superoxide, 119, 128, 352 Superoxide Dismutase, 119, 128, 352 Supplementation, 114, 175, 352 Suppression, 50, 89, 100, 164, 186, 200, 204, 352 Suspensions, 221, 352 Sweat, 297, 352 Sweat Glands, 297, 352 Sympathetic Nervous System, 226, 282, 332, 352 Sympathomimetic, 274, 277, 297, 299, 303, 322, 329, 335, 352 Symphysis, 289, 340, 352 Symptomatic, 41, 54, 276, 352 Symptomatic treatment, 276, 352 Symptomatology, 110, 352 Synapsis, 353 Synaptic Transmission, 24, 55, 329, 353 Synaptic Vesicles, 190, 353 Synaptosomes, 20, 142, 353 Synchrony, 30, 353 Synergistic, 165, 216, 339, 353, 355 Systemic, 13, 43, 47, 210, 228, 246, 277, 280, 284, 292, 296, 299, 303, 311, 315, 353, 357, 358 Systolic, 313, 353 T Tachycardia, 299, 353
Tandem Repeat Sequences, 137, 353 Tardive, 119, 169, 199, 220, 280, 353 Technetium, 184, 207, 353 Telangiectasia, 257, 353 Telencephalon, 283, 288, 353 Temperament, 10, 354 Temporal, 7, 8, 15, 29, 32, 45, 55, 277, 311, 312, 321, 354 Temporal Lobe, 277, 354 Tendon, 308, 354 Teratogenic, 276, 354 Testis, 304, 354 Testosterone, 343, 354 Tetrahydrocannabinol, 85, 223, 354 Tetrahydronaphthalenes, 177, 354 Thalamic, 43, 53, 80, 282, 303, 354 Thalamic Diseases, 282, 354 Thalamus, 43, 53, 295, 303, 319, 338, 354 Therapeutics, 9, 24, 44, 46, 113, 114, 120, 127, 133, 161, 206, 226, 233, 247, 354 Thermal, 72, 186, 210, 298, 354 Third Ventricle, 303, 314, 354 Thoracic, 297, 354 Threshold, 186, 305, 313, 354 Thrombin, 336, 340, 354 Thrombocytes, 336, 354 Thrombomodulin, 340, 354 Thrombopenia, 196, 355 Thrombosis, 340, 351, 355 Thromboxanes, 281, 301, 355 Thyroid, 313, 317, 355, 357 Thyroid Gland, 313, 355 Thyroid Hormones, 355, 357 Thyrotropin, 71, 90, 355 Thyroxine, 335, 355 Tic, 197, 228, 355 Time Perception, 7, 355 Tissue Transplantation, 39, 355 Tobramycin, 76, 355 Tolerance, 14, 22, 141, 274, 285, 355 Tomography, 11, 44, 51, 54, 76, 87, 88, 89, 96, 117, 155, 232, 235, 355 Tone, 74, 75, 158, 282, 325, 355 Tonic, 6, 284, 286, 355 Tonicity, 301, 355 Tonus, 355 Tooth Preparation, 274, 356 Topical, 281, 304, 313, 356 Torsion, 237, 315, 356 Torticollis, 237, 356 Toxicity, 11, 13, 53, 84, 118, 136, 156, 165, 166, 193, 300, 322, 356
380
Dopamine
Toxicology, 17, 23, 50, 143, 151, 165, 254, 356 Toxin, 17, 211, 212, 303, 355, 356 Trace element, 307, 356 Traction, 290, 356 Transcriptase, 61, 356 Transcription Factors, 35, 356 Transdermal, 221, 227, 356 Transduction, 27, 35, 349, 356 Transfection, 284, 302, 309, 356 Translation, 34, 341, 356 Translational, 356 Translocation, 19, 84, 356 Transmitter, 48, 61, 72, 273, 281, 282, 299, 305, 317, 321, 329, 353, 356 Transplantation, 23, 39, 77, 80, 90, 91, 290, 314, 356 Trauma, 58, 207, 231, 296, 327, 328, 343, 356 Treatment Outcome, 102, 356 Tremor, 193, 225, 237, 322, 332, 357 Triad, 193, 357 Tricuspid Atresia, 294, 357 Tricyclic, 205, 235, 274, 357 Trigeminal, 27, 357 Trigger zone, 280, 357 Tryptophan, 10, 36, 292, 348, 357 Tryptophan Hydroxylase, 10, 357 Tubercle, 14, 329, 357 Tuberous Sclerosis, 257, 357 Tumor Necrosis Factor, 93, 357 Tumour, 308, 357 Type 2 diabetes, 211, 357 U Ubiquitin, 53, 106, 357 Ulcer, 211, 212, 357 Ulceration, 3, 333, 357 Unconditioned, 60, 357 Uranium, 353, 357 Urea, 4, 220, 238, 352, 358 Uremia, 344, 358 Ureters, 318, 358 Urethra, 333, 340, 358 Uric, 238, 310, 314, 358 Urinary, 137, 181, 290, 303, 315, 325, 358 Urine, 236, 238, 284, 295, 304, 312, 315, 318, 327, 344, 358 Urobilinogen, 238, 358 Uterus, 289, 294, 296, 328, 339, 358 V Vaccine, 340, 358 Vacuoles, 302, 358
Vagina, 289, 297, 358 Vagus Nerve, 237, 349, 358 Valine, 333, 358 Vascular, 4, 213, 226, 276, 277, 290, 297, 302, 311, 315, 323, 329, 336, 355, 358 Vascular Resistance, 226, 277, 358 Vasoactive, 76, 176, 358 Vasoactive Intestinal Peptide, 76, 176, 358 Vasoconstriction, 186, 226, 299, 303, 358 Vasodilation, 186, 236, 299, 358 Vasodilator, 206, 277, 285, 299, 312, 323, 359 Vasodilator Agents, 206, 359 Vasopressor, 135, 359 VE, 114, 156, 223, 359 Vector, 33, 79, 81, 356, 359 Vein, 278, 281, 317, 329, 359 Venous, 186, 281, 284, 288, 340, 357, 359 Venous blood, 284, 288, 359 Venter, 359 Ventral Tegmental Area, 12, 30, 31, 43, 45, 47, 49, 57, 62, 82, 93, 359 Ventricle, 277, 282, 287, 294, 312, 329, 341, 353, 354, 357, 359 Ventricular, 277, 294, 353, 357, 359 Vesicular, 8, 13, 19, 33, 63, 119, 359 Vestibule, 291, 316, 347, 359 Vestibulocochlear Nerve, 282, 359 Veterinary Medicine, 221, 228, 253, 359 Viral, 62, 75, 138, 237, 302, 356, 359 Viral vector, 75, 359 Virulence, 282, 356, 359 Virus, 23, 33, 74, 79, 80, 82, 288, 303, 309, 345, 356, 359, 360 Viscera, 350, 360 Visceral, 4, 282, 319, 324, 328, 358, 360 Visceral Afferents, 282, 358, 360 Visual field, 330, 345, 360 Vitamin A, 140, 316, 345, 360 Vitreous, 290, 345, 360 Vitreous Body, 290, 345, 360 Vitro, 9, 12, 38, 41, 42, 50, 51, 71, 90, 110, 120, 143, 147, 156, 158, 159, 160, 175, 178, 182, 186, 215, 309, 312, 315, 360 Vocal cord, 310, 360 Volition, 317, 360 Vomeronasal Organ, 330, 360 W Wakefulness, 130, 296, 360 War, 228, 337, 360 White blood cell, 279, 320, 325, 336, 360
381
Withdrawal, 21, 47, 82, 85, 166, 199, 215, 296, 360 Wound Healing, 287, 360 X Xenobiotics, 192, 193, 360 Xenograft, 278, 360
X-ray, 293, 307, 321, 329, 361 Y Yeasts, 307, 335, 361 Z Zymogen, 340, 361
382
Dopamine
383
384
Dopamine
