HALOPERIDOL 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., 1960Haloperidol: 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: 0-497-00508-5 1. Haloperidol-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 haloperidol. 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 HALOPERIDOL .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Haloperidol.................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 48 The National Library of Medicine: PubMed ................................................................................ 49 CHAPTER 2. NUTRITION AND HALOPERIDOL................................................................................. 95 Overview...................................................................................................................................... 95 Finding Nutrition Studies on Haloperidol .................................................................................. 95 Federal Resources on Nutrition ................................................................................................... 97 Additional Web Resources ........................................................................................................... 98 CHAPTER 3. ALTERNATIVE MEDICINE AND HALOPERIDOL .......................................................... 99 Overview...................................................................................................................................... 99 National Center for Complementary and Alternative Medicine.................................................. 99 Additional Web Resources ......................................................................................................... 108 General References ..................................................................................................................... 109 CHAPTER 4. DISSERTATIONS ON HALOPERIDOL .......................................................................... 111 Overview.................................................................................................................................... 111 Dissertations on Haloperidol ..................................................................................................... 111 Keeping Current ........................................................................................................................ 112 CHAPTER 5. PATENTS ON HALOPERIDOL ..................................................................................... 113 Overview.................................................................................................................................... 113 Patents on Haloperidol............................................................................................................... 113 Patent Applications on Haloperidol........................................................................................... 117 Keeping Current ........................................................................................................................ 118 CHAPTER 6. BOOKS ON HALOPERIDOL......................................................................................... 121 Overview.................................................................................................................................... 121 Chapters on Haloperidol............................................................................................................. 121 CHAPTER 7. PERIODICALS AND NEWS ON HALOPERIDOL ........................................................... 123 Overview.................................................................................................................................... 123 News Services and Press Releases.............................................................................................. 123 Newsletter Articles .................................................................................................................... 125 Academic Periodicals covering Haloperidol ............................................................................... 125 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 127 Overview.................................................................................................................................... 127 U.S. Pharmacopeia..................................................................................................................... 127 Commercial Databases ............................................................................................................... 128 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135 Other Commercial Databases..................................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Finding Associations.................................................................................................................. 141 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 143 Overview.................................................................................................................................... 143 Preparation................................................................................................................................. 143 Finding a Local Medical Library................................................................................................ 143
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Medical Libraries in the U.S. and Canada ................................................................................. 143 ONLINE GLOSSARIES................................................................................................................ 149 Online Dictionary Directories ................................................................................................... 149 HALOPERIDOL DICTIONARY................................................................................................. 151 INDEX .............................................................................................................................................. 213
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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 haloperidol 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 haloperidol, 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 haloperidol, 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 haloperidol. 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 haloperidol, 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 haloperidol. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON HALOPERIDOL Overview In this chapter, we will show you how to locate peer-reviewed references and studies on haloperidol.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and haloperidol, 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 “haloperidol” (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: •
Double-Blind Comparison of Trazodone and Haloperidol for Treatment of Agitation in Patients With Dementia Source: American Journal of Geriatric Psychiatry. 5(1): 60-69. Winter 1997. Summary: This article compares the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty- eight older patients with dementia and agitated behaviors were randomly assigned to doubleblind treatment with either trazodone or haloperidol for 9 weeks. The results suggest that there was no significant difference in improvement between the medication groups; however, adverse effects were more common in the group treated with haloperidol. Improvements in individual areas suggest that repetitive, verbally aggressive, and oppositional behaviors respond preferentially to trazodone. Symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol.
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The authors conclude that moderate doses of each drug may be equally effective for treating overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent. 1 figure, 3 tables, 55 references. (AAM). •
Randomized, Placebo-Controlled Dose-Comparison Trial of Haloperidol for Psychosis and Disruptive Behaviors in Alzheimer's Disease Source: American Journal of Psychiatry. 155(11): 1512-1520. November 1998. Summary: This article describes a study that compared the efficacy and side effects of two doses of haloperidol and placebo in treating psychosis and disruptive behaviors in 71 outpatients with Alzheimer's disease (AD). In Phase A, researchers compared the standard 2 to 3 mg daily dose of haloperidol with a low dose (0.50 to 0.75 mg per day) in patients with AD. In Phase B, patients on haloperidol were switched to placebo and patients on placebo were randomly assigned the low or standard haloperidol dose. Phase A data showed that standard-dose haloperidol was efficacious and superior to low-dose haloperidol and to placebo for psychosis factor and psychomotor agitation scores on a rating scale. The advantage of standard dose over low dose was replicated in Phase B. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. Researchers concluded that these results indicated a favorable therapeutic profile for standard-dose haloperidol, although a subgroup developed moderate to severe extrapyramidal signs. The narrow therapeutic window observed with haloperidol may apply to other neuroleptic drugs used in AD patients with psychosis and disruptive behaviors. 1 figure, 2 tables, 53 references.
•
Aggression in the Demented Patient: A Double-Blind Study of Loxapine Versus Haloperidol Source: International Clinical Psychopharmacology. 8(2): 103-108. Summer 1993. Summary: This journal article describes a double blind study that compared the efficacy and side effects of loxapine and haloperidol when used to treat aggression in patients with dementia. Forty patients admitted to a specialized geriatric psychiatry inpatient unit were randomly assigned to treatment with either loxapine or haloperidol. Dosages were adjusted using an optimizing dosage regime. The frequency of aggressive acts and the number and nature of emergent side effects were measured over a 28 day period. Among patients who completed the study, 14 of 17 patients receiving loxapine and 11 of 14 patients receiving haloperidol showed a decrease in their weekly aggression frequency. The response rate was not significantly different between groups. However, patients receiving haloperidol experienced significantly more side effects such as dry mouth, rigidity, and oversedation than did those receiving loxapine. In addition, there was a trend for the side effects of haloperidol to be more severe than those seen with loxapine. 16 references.
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Randomized Trial of Risperidone, Placebo, and Haloperidol for Behavioral Symptoms of Dementia Source: Neurology. 53: 946-955. September 1999. Summary: This journal article describes a randomized trial comparing the efficacy and tolerability of risperidone with placebo, and the tolerability of haloperidol as treatment for aggression and other behavioral symptoms in patients with dementia. After a 1week washout period, 344 dementia patients were randomly assigned to receive placebo or flexible doses of risperidone or haloperidol for 12 weeks. Efficacy and tolerability
Studies
5
assessments were conducted at selection, baseline, and weeks 1, 2, 4, 6, 8, 10, and 12. The primary end point was defined as the percentage of patients with a 30 percent or greater improvement on a standard behavioral measure. The mean dose at end point was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Risperidone resulted in a greater reduction in the severity and frequency of behavioral symptoms, particularly aggression, than did placebo. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. The authors conclude that low-dose risperidone appears to be well tolerated and effective for reducing the behavioral symptoms of dementia. 4 figures, 4 tables, 39 references. •
Alprazolam as an Alternative to Low-Dose Haloperidol in Older, Cognitively Impaired Nursing Facility Patients Source: Journal of the American Geriatrics Society. 46(5): 620-625. May 1998. Summary: This journal article describes a study comparing alprazolam with low-dose haloperidol for the management of disruptive behaviors associated with dementia, delirium, amnesia, and other cognitive disorders. The participants were 48 patients, aged 65 to 98 years, from 25 nursing homes in western Washington state, who were receiving haloperidol at a dose of 1 mg or less per day for agitation and behavioral disturbances. A randomized, double blind, crossover design, with two 6-week treatment periods, was used to compare alprazolam 0.5 mg twice daily to the current haloperidol regimen. The patients were assessed at baseline and the end of each treatment period. The outcomes of interest were the number of behavioral episodes, activities of daily living as measured by the Blessed Dementia Scale, extrapyramidal symptoms measured by the Abnormal Involuntary Movement Scale, and psychopathology measured with the Clinical Global Impressions and the Sandoz Clinical Assessment-Geriatric scales. No significant differences were bserved between alprazolam and haloperidol on the number of behavioral episodes or, with few exceptions, the other outcome measures. The authors conclude that alprazolam may be as effective as haloperidol for the treatment of agitation and other behavioral problems associated with dementia and related cognitive disorders. 3 tables, 44 references.
Federally Funded Research on Haloperidol The U.S. Government supports a variety of research studies relating to haloperidol. 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 haloperidol.
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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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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 haloperidol. The following is typical of the type of information found when searching the CRISP database for haloperidol: •
Project Title: ALPHA 2 AGONIST PLUS A CHOLINESTERASE INHIBITOR IN ALZHEIMERS DISEASE Principal Investigator & Institution: Davis, Kenneth L.; Professor and Chairman; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002 Summary: Cholinomimetic therapies for AD (Alzheimer's disease) have met with only limited success. Although a sub-group of patients have a modest, albeit clinically significant improvement with cholinesterase inhibitors, this is hardly as a robust a treatment as L-dopa for Parkinson's disease or even haloperidol for schizophrenia. Clearly, one problem with a purely cholinergic approach to the psychotherapeutics of AD is that AD is not simply a cholinergic deficit. Evidence for a noradrenergic deficit in AD derives from studies which demonstrate a loss of LC neurons, most evident among subjects with the greatest neurocortical plaque formation and is correlated with severity of dementia. Furthermore, norepinephrine content in several brain areas is reduced and this reduction is associated with greater severity of intellectual deterioration among patients with AD. Thus, there are compelling data to indicate probably influence the symptoms of the disease and the efficacy of a strictly cholinergic approach. Despite the development of safe, easier to use cholinesterase inhibitors, such as Aricept, only a portion of treated patients have a modest effect. Evaluation of the data from Phase III trials of Aricept shows that 62.3% of substantial numbers of non- responders to a purely cholinergic approach to treatment therefore necessitate the need to develop alternative approaches. Animal studies provide convincing evidence to support such an alternative approach, particularly one which enhances both cholinergic and noradrenergic activity. Therefore, our overall aim to determine whether the co- administration of the selective alpha-2 noradrenergic receptor agonist, guanfacine, with the acetylcholinesterase inhibitor, Aricept, is clinically more effective in treating cognitive symptoms of Alzheimer's disease than administration of Aricept alone. We propose to treat 72 AD subjects in a 14 week double blind, placebo controlled, parallel design, protocol, with an additional 3 week placebo washout phase. Subjects will be treated with a combination on measures of cognitive and global functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALPHA-SYNUCLEIN PARKINSONISM
&
DOPAMINE:IMPLICATIONS
FOR
Principal Investigator & Institution: Perez, Ruth G.; Associate Professor; Neurology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Parkinson's disease (PD) is characterized by a loss of dopamine (DA) neurons in substantia nigra and an accumulation of a-synuclein in Lewy bodies, the cytoplasmic inclusions of PD. These and other observations suggest that an understanding of the role of a-synuclein in these processes will provide insights into the pathogenesis of PD. Although the function of this protein is unknown, a-synuclein is likely to be a chaperone. This is suggested by a-synuclein's native unfolded structure, its ability to interact with several key cellular proteins, and its homology to 14-3-3, a family
Studies
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of molecular chaperones. One of the proteins to which 14-3-3 binds is tyrosine hydroxylase (TB), the rate limiting enzyme in catecholamine synthesis. The binding of 14-3-3 to TH occurs primarily to a phosphorylated serine (Ser19) in the N-terminal regulatory domain of the enzyme. The binding of 14-3-3 to Ser19 is required to increase the enzyme's activity and this activation correlates with an increase in catecholamine synthesis. An interaction of 14-3-3 with Ser40 on TH has recently been reported. We have preliminary data suggesting that: (1) a-synuclein and TB interact with each other in brain and in a dopaminergic cell line, (2) the addition of recombinant a-synuclein inhibits TH activity in an in vitro model of TH activity, and (3) overexpression of asynuclein in a dopaminergic cell line inhibits TH activity, TH phosphorylation, and DA synthesis. Together these data suggest a key role for a-synuclein in TB regulation and link a-synuclein with the regulation of DA synthesis, storage, and release. Thus, the overall goal of this proposal is to explore the role of a-synuclein in TH regulation and DA synthesis and its impact on dopaminergic cell function under normal and pathophysiological conditions. To achieve this goal we propose three specific aims: (1) To test the hypothesis that a-synuclein inhibition of TH activity is associated with TH Ser19 and Ser40 phosphorylation.(2) To test the hypothesis that a-synuclein-induced TH-inhibition reduces DA release and that the absence of a-synuclein increases DA synthesis and release.(3) To test the hypothesis that a loss of a-synuclein-mediated inhibition of TH is associated with ROS formation and reduced cell viability. Using a unique combination of in vitro and in vivo approaches, our studies hold promise to expand both our basic understanding of TH regulation and provide further insight into the association between a-synuclein and TH as they relate to several abnormal conditions, including PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION
AMYGDALOSTRIATAL
CIRCUIT--AFFECTIVE
BEHAVIOR--
Principal Investigator & Institution: Taylor, Jane R.; Associate Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 16-JUL-2002; Project End 30-JUN-2006 Summary: Neurobiological studies of major depression have identified dysfunctional cognitive-affective-motor regions; however, the details of these altered physiological and structural changes, and the molecular basis for these alterations, remain to be elucidated. Recent imaging data suggest that depressed patients have increased blood flow/metabolism in the amygdala concomitant with decreased blood flow and volume in orbitofrontal cortex and ventromedial striatum. These effects may be relevant to the psychopathology of depression because cortico-limbic - striatal dysfunction may contribute to hypersensitive stress, fea4r, and anxiety responses, anhedonia, affective alterations, and changes in cognitive function. Thus, it is critical to understand the molecular basis of neuroplasticity in these brain regions implicated in depression and mood disorders and the resulting cellular and behavioral correlates. This project will thus focus on the role for the extended amygdala (notably the central nucleus of the amygdala, and nucleus accumbens shell) in depression and alterations in PKA/CREB signaling in these regions because the involvement of PKA/CREB in learning/plasticity is well established and because antidepressant treatment increases PKA/CREB activity. Specifically the functional and molecular correlates of plasticity in response to stress and antidepressant treatment will be investigated. We hypothesize that alterations in the extended amygdala results in abnormal processing of affective/emotional stimuli and behavioral regulation by appetitive and aversive events. Combined with alterations of
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neural signaling within the ventral striatum that contribute to anhedonia, negative stimuli may also exert heightened suppressive consequences on behavior in depression. In addition, sustained increases PKA/CREB produced by anti-depressants would be predicted modify behavior by enhancing plasticity associated with learning and affective processes. Using direct pharmacological manipulations, transgenic murine models, vector-mediated over-expression of CREB and stress-induced animal models of depression, we will investigate the role of PKA/CREB signaling within the extended amygdala in reactivity to unconditioned aversive stimuli and/or anhedonia (sensitivity to appetitive rewards), and appropriate control procedures, as well as the mechanism of action of anti-depressant drugs in order to evaluate and validate the relevance of these processes to models of depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIPSYCHOTIC DISCONTINUATION IN ALZHEIMER S DISEASE Principal Investigator & Institution: Devanand, Davangere P.; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Antipsychotic medications have been shown to be efficacious in the treatment of patients with Alzheimer s disease who have psychotic symptoms or behavioral dyscontrol (called behavioral complications here). However, these medications have a variety of short and long-term side effects. Although their prolonged effects in AD patients are not established, Federal (OBRA) regulations have mandated periodic discontinuation of antipsychotic medications in nursing homes. Surprisingly, there is little empirical evidence to support or refute this approach in nursing homes or in outpatients. In an NIMH-funded study (R01 MH55735) at the NYSPl/Columbia site, AD outpatients with behavioral complications receive open treatment with haloperidol for 20 weeks. Responders are randomized, double-blind, to continuation haloperidol or placebo. Patients on placebo have shown a significantly higher relapse rate (80%) than patients who continue on haloperidol (44.4% relapse in intent-to-treat analyses, and 22.2% relapse using a restricted definition of relapse). The study's limitations are the small number of subjects (19 responders randomized) and the use of haloperidol, a conventional antipsychotic that commonly causes extra pyramidal signs (EPS), and is associated with a high risk of tardive dyskinesia (TD) with prolonged use. The proposed multicenter study (four academic sites; nursing homes and outpatients) will address these limitations by studying a relatively large number of AD patients using an atypical antipsychotic, risperidone, which has less neurological side effects than haloperidol. Other reasons for studying extended treatment with an atypical antipsychotic include the risk of medication toxicity and the expense of taking these medications. The study design has two phases. In Phase 1, 200 AD patients with behavioral complications will receive open treatment with risperidone for 16 weeks. Responders will be randomized, double-blind, to one of three arms in Phase 2:(1) continuation risperidone for the next 32 weeks, (2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or (3) placebo for the next 32 weeks. We hypothesize that in Phase 2, during the first 16 weeks, the time to relapse will be significantly shorter on placebo than on risperidone, and that the relapse rate on placebo will be significantly greater than the relapse rate on risperidone. This design will provide useful data on the efficacy and side effects of longer-term treatment with risperidone, and provide critical information about the likelihood and time to relapse, as well as predictors of relapse, in patients switched from risperidone to placebo. This information is essential to guide the clinician toward optimal use of such medications in one of the most challenging types of
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patients: the AD patient with psychosis or behavioral dyscontrol. The results will be of considerable value to the practicing clinician and have substantial implications for the regulatory oversight of elder care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIPSYCHOTIC MEDICATION Principal Investigator & Institution: Newcomer, John W.; Associate Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 20-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Type 2 diabetes mellitus is characterized by disturbances in insulin action on skeletal muscle, liver and adipose tissue. Diabetes causes increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-tenn (e.g., cardiovascular disease) complications. The combination of hyperglycemia, dyslipidemia and abdominal adiposity is even more strongly associated with increased cardiovascular morbidity and mortality. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications, suggesting that these patients may be at increased risk. Since then, however, additional glucoregulatory abnormalities (e.g., new Onset diabetes), dyslipidemia, and increased weight and adiposity have all been associated with antipsychotic medications. Concern about antipsychotic effects on glucose, lipids and adiposity has increased recently, focusing on the widely-used newer medications, clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin sensitivity and antipsychotics can increase adiposity. However, medication effects on glucose control and insulin action may also occur independent of differences in adiposity. This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected ant:ipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of gold-standard stable isotopetracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients treated with olanzapine and risperidone (from groups above), crossed over to treatment with the other agent for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIPSYCHOTICS AND ALCOHOL DRINKING IN RODENTS Principal Investigator & Institution: Green, Alan I.; Professor; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2004; Project Start 13-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Patients with schizophrenia (SCH) commonly develop alcohol use disorders. While typical antipsychotic drugs (e.g., haloperidol -
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Haloperidol
HAL) do not control alcohol use in these patients, recent data suggest that the atypical antipsychotic clozapine (CLOZ) does. We recently presented a neurobiologic formulation suggesting: (a) that persons with SCH have a dysfunction in their dopamine (DA) mediated mesocorticolimbic reward pathways underlying alcohol use; (b) that most antipsychotic drugs (e.g., HAL) do not decrease alcohol use in this population because they do not restore the normal function of these pathways; but (c) that CLOZ, through its actions on multiple neurotransmitter systems, particularly its potent blockade of alpha 2 noradrenergic receptors, as well as its weak blockade of DA D2 receptors, has a normalizing effect on the signal detection capability of these pathways. To further elucidate the differential effects of HAL and CLOZ, we recently initiated a study in Syrian golden hamsters, an outbred animal that drinks large amounts of alcohol. Our initial data indicate that CLOZ but not HAL substantially decreases hamster alcohol drinking. In this R03 proposal, we seek to expand our investigations and prepare for submission of an R01 proposal. We will continue studies of the hamster, but will also expand to include the "P" rat, a genetically- bred strain that has been proposed as an excellent animal model for alcoholism. Our overarching hypothesis is that CLOZ's effect in alcohol-preferring animals, as in patients with SCH and comorbid alcohol use disorder, relates to its action in DA-mediated mesolimbic circuits. The primary specific aim seeks: (1) To determine whether CLOZ will decrease alcohol drinking more than HAL does in the P rat, a rodent with known dysfunction in the DAmediated mesolimbic system. The other aims are designed to further inform the neurobiologic basis by which CLOZ, but not HAL, limits alcohol use in the hamster and, potentially, in the P rat: (2) To explore whether loss of suppression of alcohol drinking develops during long-term treatment with CLOZ; and (3) to begin to explore (a) whether addition of a potent D2 antagonist to CLOZ will lessen the CLOZ's ability to suppress alcohol drinking, and (b) whether addition of a potent alpha 2 antagonist to HAL will allow HAL to suppress alcohol drinking. The long-term goal of our research is to create better treatments for alcoholism in patients with SCH (and possibly even in those without SCH). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MACHINERY
ANTIPSYCHOTICS
AND
RECEPTOR
DESENSITIZATION
Principal Investigator & Institution: Gurevich, Eugenia V.; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 05-DEC-2000; Project End 30-NOV-2003 Summary: (Adapted from applicant's abstract) Arrestins and G protein-coupled receptor kinases (GRKs) participate in homologous desensitization of hundreds of G proteincoupled receptors (GPCRs). The rate and extent of desensitization of GPCRs is sensitive to the concentration of arrestins and GRKS in the cells. In its turn, the amount of arrestins and/or GRKs can be modulated by activity of GPCRs. Typical antipsychotic drugs are potent antagonists of the D2 dopamine receptor, whereas atypical drugs interact with several GPCRs. Plasticity of several GPCRs is implicated in schizophrenia pathology and actions of antipsychotic drugs. The a[[;ocamts hypothesize that treatment with antipsychotics induces alterations in the concentration of specific arrestins and/or GRKs in selected brain regions, thereby modifying signal transduction via GPCRs in these regions. Exploration of this hypothesis is clinically relevant because molecular mechanisms of the beneficial actions of antipsychotic drugs remain elusive. Mechanism of action of atypical antipsychotics with their higher efficacy against negative symptoms and cognitive deficits is of particular interest. The specific aims designed to test this
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hypothesis include determination of the repertoire of arrestin and GRK proteins in specific subtypes of output neurons in the striatum and nucleus accumbens, the brain regions that are prime targets of antipsychotics. The second specific aim focuses on comparison of the effects of acute and subchronic treatment with typical antipsychotic haloperidol and atypical drug clozapine on the expression of arrestin and GRK mRNAs and proteins in various brain areas implicated in schizophrenia pathology and action of antipsychotics. The third specific aim is to determine whether alterations in the arrestin and GRK expression are associated with development of tardive dyskinesia induced by chronic treatment with haloperidol. Plasticity of neuronal receptor trafficking system produced by antipsychotic treatment may lead to changes in the concentrations of specific GPCRs and, ultimately, to long-term modulations of neuronal responses to endogenous stimuli and exogenous drugs. Specific modifications in the arrestin/GRK expression may thus be essential for the beneficial or side effects of antipsychotic drugs. We expect that the information gained by examining the response of the key components of the receptor trafficking machinery to antipsychotics will be helpful for targeted design of drugs with improved clinical profile. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION
ANTIPSYCHOTICS:
TEMPORAL
EFFECTS
ON
COGNITIVE
Principal Investigator & Institution: Terry, Alvin V.; Clinical & Administrative Pharmacy; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Schizophrenia is a debilitating illness that affects up to 1% of the world's population. While the use of antipsychotic (neuroleptic) drugs is the standard of care for treating the psychotic symptoms of the illness, little is known regarding which neuroleptics are best for extended use in those with cognitive impairment. This consistent feature of schizophrenia is now believed to have the most substantial impact on the longterm outcome of the disease. Accordingly, a major longterm goal of this laboratory is to develop mechanistically-based therapeutic strategies for patients suffering from psychotic symptoms and cognitive dysfunction. The objective of this application is to establish potential relationships between the cellular and biochemical effects of chronic neuroleptic exposure and cognitive function in an experimental animal model. We have compelling preliminary evidence from rat studies that chronic exposure to conventional neuroleptics such as haloperidol (in a temporally dependent fashion), but not atypical agents such as clozapine, leads to cognitive impairment and that a reduction in a key marker for cholinergic neurons, choline acetyltransferase, precedes the cognitive symptoms. Due to the pattern of reduced cholinergic enzyme staining and the fact that many of the cholinergic neurons involved in learning and memory are functionally dependent on the neurotrophin, nerve growth factor (NGF), we have developed the hypothesis that chronic exposure to conventional, but not atypical, neuroleptics in rats decreases neurotrophic support to cholinergic neurons, resulting in decreased cholinergic activity in the brain and impairment of cognitive function. The rationale for the proposed animal studies is that a better understanding of the differential (chronic) effects of neuroleptics on memory function will facilitate future (clinical) efforts to identify optimal drugs for cognitively impaired psychiatric patients. To test the hypothesis we propose two specific aims: 1): To evaluate differential temporal effects of different classes of neuroleptic drugs on cognitive function in an experimental animal model. 2): To define potential correlative relationships between neuroleptic-induced cognitive changes and temporal changes in
12
Haloperidol
biochemical and cellular parameters of cholinergic function in the brain, NGF release, and NGF receptor expression. We will use a water maze task to measure spatial learning, an 8-arm radial arm maze task to assess working memory, and in situ hybridization, western blots, ELISA experiments, immunofluorescence staining, and receptor autoradiography to measure the expression of NGF and key cholinergic markers. We expect that chronic exposure to conventional, but not atypical neuroleptics will negatively affect both spatial learning and working memory and that neurolepticinduced alterations in CNS cholinergic activity will both precede and correlate with detectable manifestations of cognitive dysfunction. These studies, designed to mechanistically define neuroleptics based on their chronic effects on specific biological substrates of memory are significant because they will contribute to the identification of therapeutic agents with optimal effects on cognitive function, and thus potentially benefit many psychiatric patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARIPIPRAZOLE IN THE TREATMENT OF PSYCHOSIS Principal Investigator & Institution: Freidhoff, Arnold; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATTENTION, WORKING MEMORY AND ANTIPSYCHOTICS USING FMRI Principal Investigator & Institution: Kindermann, Sandra S.; Psychiatry; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 11-AUG-1999; Project End 31-JUL-2004 Summary: This proposal for a Mentored Patient-focused Research Career Development award is submitted by Sandra S. Kindermann, Ph.D., Department of Psychiatry, University of California, San Diego. The objective of this 5-year academic award is to develop the candidate's expertise as a researcher, educator and clinician in general psychiatry with specialization in the differential effects of psychopharmacological agents on (1) functional brain systems, (2) treatment response, (3) selective attention and working memory performance; and (4) adaptive functioning in psychiatric patients. This award will build on the candidate's training, skills, abilities and knowledge in pharmacology, clinical psychology, neuropsychology, functional neuroimaging, clinical research and methods in geriatric psychiatry. The state objective will be achieved by means of a structured training plan, including relevant coursework and consultation with leading experts in the fields of psychopharmacology., geriatric psychiatry and brain imaging. The research plan compares the effects across time of haloperidol compared to risperidone on brain systems involved in selective attention and working memory, therapeutic response and level of adaptive functioning and their interrelationships. The study will provide preliminary cross-sectional and longitudinal comparisons among older patients with schizophrenia receiving either haloperidol or risperidone who are prospectively categorized as functioning adaptively or not. The association between treatment response and brain function will also be examined separately for each treatment group. For the brain functioning analysis, key variables (accuracy and reaction time performance for the selective attention and working memory tasks) will be measured concurrently with region and intensity of brain
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13
activation time-locked to the experimental task. The study will use patients randomized to haloperidol or risperidone from an ongoing boule-blind study. Imaging, behavioral, symptom severity and adaptive functioning data will be acquired at Time 1 when a patient enters the randomized double-blind study and again at Time 2 after 12 weeks of treatment. This training program will assist the candidate in making the transition to independent investigator at the University of California, San Diego, and provide the foundation for a long-term research program focused on the interaction of psychopharmacology and brain function of older patients with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOPHYSICAL STUDY OF ANTIPSYCHOTICS BEHAVIORAL EFFECTS Principal Investigator & Institution: Fowler, Stephen C.; Professor; Human Develmt and Family Life; University of Kansas Lawrence Youngberg Hall Lawrence, Ks 660457563 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) The atypical antipsychotic drugs are a major advance over the older drugs that frequently induced extrapyramidal side effects (EPS). These newer drugs, except for clozapine, continue to induce EPS at higher doses. Despite its superior efficacy in the treatment of refractory schizophrenic patients, clozapine produces measurable cognitive side effects as well as distinctive, but not EPSlike, motor effects in both humans and rats. The over arching purpose of this proposal is to quantify, in rats and in inbred strains of mice, the motor and cognitive side effects of clozapine and other atypical antipsychotic drugs as well as to continue efforts to quantitate low-dose EPS in rodents. Three, primary behavioral measurement procedures will be used: 1) the food-anticipation-operant-microcatalepsy (FAOM) task that models low dose EPS (bouts of immobility that interrupt behavior) and bradykinesia (slowing of movements) in both rats and mice; 2) the sustained attention task (SAT) that concurrently measures reaction time and cognitive performance and closely resembles the continuous performance task that reveals deficits characteristic of schizophrenia; 3) the forelimb tremor task (FT) that uses force-transducer technology and Fourier analysis to quantify drug-induced tremor and detects the hypotonia and antitremor effects of clozapine. In the FAOM procedure, the EPS liability of atypical antipsychotics clozapine, risperidone, sertindole, quetiapine, and olanzapine will be evaluated in haloperidolsensitized rats. When haloperidol-treated inbred strains of mice were compared in the FAOM task, the C57bl/6 mice showed striking EPS-like effects while the Balb/c mice did not-a result suggesting genetic causes. Several inbred strains of mice will be compared to identify strains likely to express EPS-like effects of atypical antipsychotic drugs. The SAT procedure will be used with rats to assess deleterious cognitive effects of chronic clozapine. The FT task will be used with rats to explore clozapine's recently discovered withdrawal effect (tremor rebound), to evaluate other atypical antipsychotics for clozapine-like motor effects, and to assess clozapine's ability to dampen tremor induced by harmaline or physostigmine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BLOOD FLOW CHANGES AND ANTIPSYCHOTIC DRUG ACTION Principal Investigator & Institution: Lahti, a C.; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-JAN-2003
14
Haloperidol
Summary: (adapted from applicant's abstract): Antipsychotic drugs reduce psychosis, induce motor effects, and have miscellaneous other actions. The brain substrates of these effects, beyond actions on receptor populations are poorly understood. The investigator proposes to determine the dynamic time course of the effects of antipsychotics on regional cerebral blood flow (rCBF) using PET and 15OH2 in drug-free schizophrenia patients as a direct pharmacodynamic assessment of drug action in the human brain. rCBF measurements would span the pharmacokinetic time course. The investigator proposes to characterize the dynamic time course of rCBF alterations following the acute and six days of administration of two different antipsychotic drugs, the traditional antipsychotic haloperidol and the newer antipsychotic olanzapine. The ability of the changes in rCBF following acute and subacute antipsychotic administration to predict subsequent treatment response would also be evaluated. Based on their preliminary findings, the investigators hypothesize that acute and subacute drug-induced rCBF changes in selected regions will predict treatment response for positive symptoms (anterior cingulate and medial frontal cortex), for negative symptoms (middle frontal cortex and inferior parietal cortex), and motor side effects (basal ganglia). The proposed subacute drug administration regimen would approximate a pharmacokinetic steady state for both antipsychotics. An additional aim of the proposal is to compare the rCBF changes induced by haloperidol versus olanzapine during the scanning sessions obtained with acute and subacute (steady state) antipsychotic administration. The investigator proposes that the pattern of activation in the basal ganglia will best discriminate the two antipsychotic agents. These studies will hopefully provide rCBF correlates of antipsychotic activity. This information will allow the development of hypotheses related to drug mechanism of action, as well as potential surrogate markers of drug action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN ERPS AND COGNITIVE DEMAND IN SCHIZOPHRENIA Principal Investigator & Institution: Bruder, Gerard E.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 28-FEB-2004 Summary: (Adapted from applicant's abstract): Schizophrenic patients have shown a reduction in amplitude of the P3 brain ERP to tones, which was maximal over left temporal lobe sites. In the initial project period, the investigator replicated this finding in a dichotic complex tone task and found reduced N2 amplitude and asymmetry in schizophrenic patients in a dichotic syllable task. This suggests that left hemisphere dysfunction in schizophrenia for verbal processing occurs as early as 200 ms after stimulus onset. N2 abnormalities in schizophrenic patients were present in both auditory and visual tasks, whereas P3 abnormalities appear to be modality specific. The investigator proposes to conduct four studies to determine the task and patient characteristics necessary for producing these ERP abnormalities and to further resolve their neurophysiologic mechanisms. Study 1 will record ERPs in a large sample of schizophrenic patients (n=120) and normal controls (n=40) on verbal and nonverbal binaural oddball tasks, and will assess the influence of response mode (silent counting, right hand or left hand). These large samples will enable the investigator to examine the relation of ERP abnormalities in schizophrenia to symptom features, outcome of treatment with neuroleptics, familial history of schizophrenia, and neuroimaging measures. Study 2 will develop and apply new verbal and nonverbal tasks that incorporate advantages of dichotic listening procedures, but utilize a simple oddball paradigm. Study 3 compares ERPs of schizophrenic patients and controls in auditory
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and visual continuous word recognition tasks, which are thought to reflect left medial temporal lobe function. Study 4 continues the investigator's study of visuospatial processing in schizophrenia using a revised paradigm designed to disentangle effects of selective attention and later cognitive processing. Patients will be tested while off medication and again after six weeks of treatment with haloperidol or an atypical neuroleptic (clozapine or risperidone). A more long range clinical goal is to contribute toward the development of tests that could predict response to treatment with conventional or atypical neuroleptic medications for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUILDING SCHIZOPHRENIA
A
MOUSE
MODEL
WITH
RELEVANCE
TO
Principal Investigator & Institution: Fish, Kenneth N.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The career development and research program described in this proposal supports the application for a Mentored Research Scientist Development Award for Dr. Kenneth N. Fish, and is intended to provide the candidate with the background knowledge, research experience, and research management skills that will prepare him for an independent research career in schizophrenia. Training will take place at the Harold L. Dorris Neurological Research Center in the Department of Neuropharmacology (Dr. Floyd E. Bloom, Chair) of the Scripps Research Institute, under the direct supervision of Dr. Tamas Bartfai. Dr. Bartfai is highly qualified to serve as Preceptor for the Candidate, because of his experience with the methodologies to be used, his active research program in depression and schizophrenia, and his commitment to the development of junior research scientists. The Department of Neuropharmacology emphasizes a multi-disciplinary approach to problems of mental disorders. Thus, this is an ideal environment for the Candidate to materialize his goal of developing a multidisciplinary research approach to the neurobiology of schizophrenia. The overall objective of the research plan is to perform a thorough analysis of the reeler and scrambler mice to define test parameters that will be used to study new mouse models and to determine their applicability as models to study schizophrenia. Tests will include a morphological analysis of the neocortex, cerebellum, and hippocampus using three-dimensional reconstruction with NeuroZoom, immunocytochemical analysis of DA, GLU, and GABA expression, quantitative behavioral measurements [prepulse inhibition (PPI) of the startle response], and their responsiveness to clinically effective antipsychotics (haloperidol, risperidone, and clozapine). In addition, to further characterize the reeler phenotype we will generate a transgenic mouse in which reelin expression is temporally regulated and generate a mouse model that has a conditional block of reelin function to induce specific changes in brain morphology that are required to alter prepulse inhibition and/or induce ataxia. These studies will advance our understanding of how neurodevelopmental abnormalities relate to behavioral changes and will assist in the development of new antipsychotic drugs with relevance to schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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
16
Haloperidol
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 •
Project Title: CELLULAR MECHANISMS OF ANTIDEPRESSANT ACTION. Principal Investigator & Institution: Hen, Rene; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2003; Project Start 07-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The current proposal is aimed at understanding the mode of action of medications that are currently used to treat a variety of depression and anxiety-related disorders. Although selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed antidepressants and anxiolytics, their mechanisms of action, and particularly the reason for their delayed (4-6 weeks) onset of therapeutic effects, are largely unknown. The general hypothesis that we are proposing to test is that the increased hippocampal neurogenesis elicited by chronic antidepressants contributes to the behavioral effects of these drugs. We, and others, have shown that various chronic antidepressant treatments result in an increase in neurogenesis in the dentate gyrus of the hippocampus. We have also shown that a chronic antidepressant treatment decreases certain anxiety-related behavioral responses. Finally, we have developed two distinct manipulations (a genetic one and radiological one) that disrupt antidepressantinduced hippocampal neurogenesis and also suppress antidepressant-induced behavioral responses. The genetic manipulation is a deletion of the gene encoding the 5HT1A receptor; the resulting knockout mice are insensitive to the effects of SSRIs such as fluoxetine on both neurogenesis and behavior. The radiological manipulation consists of an X-irradiation of an area of the mouse brain containing the hippocampus; such a treatment prevents the effect of fluoxetine on both neurogenesis and behavior. These two sets of findings strongly suggest that the induction of neurogenesis elicited by fluoxetine in the hippocampus contributes to the behavioral effects of fluoxetine. The following experiments are designed to test this hypothesis and to establish the functional significance of adult hippocampal neurogenesis. 1. We will test the hypothesis that activation of hippocampal 5-HTIA receptors mediates the effects of fiuoxetine on neurogenesis and behavior. To accomplish this goal, we will construct "rescue" mice that express 5-HT1A receptors only in the hippocampus. 2. We will test the hypothesis that an ablation of neuronal progenitors will suppress the effects of fluoxetine. Such a finding would open new therapeutic avenues based on the stimulation of hippocampal neurogenesis, for the treatment of depression-related disorders.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLOZAPINE AND OLANZAPINE IN VIOLENT SCHIZOPHRENICS Principal Investigator & Institution: Krakowski, Menahem I.; Senior Research Scientist; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, Ny 10962 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: Chronic violence and hostility in schizophrenic patients represent a serious problem which impacts on the perpetrators, other patients and caregivers. In preliminary studies, we have identified a group of schizophrenic patients who evidence persistent violence and hostility linked to specific schizophrenic symptoms. These patients are responsible for a high percentage of all inpatient assaults. The literature suggests that clozapine (CLO) has specific anti- aggressive effects and it improves psychotic symptoms and cognitive impairments similar to those which we identified in these patients. Olanzapine's (OLZ) without the latter's potentially serious side effects suggests that it may have an important place in the treatment of these patients. We will examine the examine the comparative efficacy of CLO, OLZ and standard agent haloperidol (HAL) in the treatment of persistent. We will also how underlying symptoms and deficits are associated with persistent violence and how they improve with each of these three treatments. Violent patients (N=212) will enter a 12-week clinical trial in which they will be randomized to either CLO, OLZ or HAL under double-bind conditions. Outcomes measures include the Modified Overt Aggression Scale, the Buss-HAL under double-blind conditions. Outcomes measured include the Modified Overt Aggression Scale, the Buss-Durkee Hostility inventory, and the NOSIE. Patients' reduction in psychotic symptoms will be assessed by PANSS and CGI. Reduction in cognitive impairment will be assessed by the Wisconsin Card Sorting Test, in impulsivity by the Barrat Impulsiveness scale. It is hypothesized that: 1) the effects of CLO on physical assaults, hostility and social functioning will be superior to those of OLZ, which, in turn, will be superior to HAL's. 2) Improvement in the outcome variables-violence, hostility and social functioning-will be related to improvement in underlying symptoms, i.e. ability to utilize environmental feedback, impulsivity, and psychosis. Similar to the outcome measures, these symptoms will improve more with CLO than OLZ and more with OLZ than HAL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLOZAPINE DRUG DISCRIMINATION IN C57BL/6J MICE Principal Investigator & Institution: Philibin, Scott D.; Psychology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003; Project Start 18-AUG-2003; Project End 17-AUG-2006 Summary: (provided by applicant): Clozapine is the prototypical atypical antipsychotic drug and represents a tremendous improvement over conventional antipsychotics in terms of therapeutic efficacy and reduced side effect liability for the treatment of schizophrenia. Understanding the pharmacological properties that are important for clozapine's unique profile can help lead to the discovery of improved and safer antipsychotic drugs for the treatment of schizophrenia. One approach for investigating the molecular bases underlying the relationship of pharmacological agents and behavior has been the use of gene-targeted knockout or transgenic animals. This technique allows for the manipulation of receptors for which selective pharmacological ligands do not exist. One restriction of this approach is that most of the knockout mutations that have been developed are available only in mice - not rats. Therefore, it is necessary to have
18
Haloperidol
preclinical assays for mice in order to utilize these new and potentially powerful new techniques. The current proposal represents an important first step in this process. Twolever drug discrimination is a valuable preclinical behavioral model that has been used to investigate the discriminative stimulus properties of clozapine in rats and has helped identify neurotransmitter receptor targets for putative atypical antipsychotics. Wildtype mice (C57BL/6J) will be trained to discriminate clozapine from vehicle and then a series of atypical and typical antipsychotic drugs will be tested to determine which drugs generalize to clozapine's discriminative cue. Establishing this procedure in wildtype mice will allow for the future use of knockout and transgenic mice and will expand the tools available to molecular geneticists and behavioral pharmacologists. This will help to increase our understanding of the perplexing pharmacology of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE SELF-ADMINSTRATION: EFFECTS ON LEARNING Principal Investigator & Institution: Winsauer, Peter J.; Associate Professor; Pharmacology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONSTITUTIVELY ACTIVE SEROTONIN RECEPTORS Principal Investigator & Institution: Teitler, Milt; Professor; Pharmacology & Neuroscience; Albany Medical College of Union Univ Albany, Ny 12208 Timing: Fiscal Year 2002; Project Start 01-JUL-1997; Project End 31-MAR-2006 Summary: (provided by applicant): We have shown that clozapine and risperidone, atypical antipsychotic drugs, have potent inverse agonist properties at constitutively activated mutant (CAM) forms of the rat 5SHT2A and 5HT2C receptors. Inverse agonist activity may be a significant property of antipsychotic drugs, given the revised ternary complex model of G-protein coupled receptors (GPCR), which predicts a steady-state level of activation of receptors in the absence of ligand stimulation. Further studies of antipsychotic drug actions at CAM forms of clozapine-sensitive human SHT receptors are necessary to determine if inverse agonist activity is a key property of atypical antipsychotic drugs. In order to expand the studies to the human 5HT6 and 5HT7 receptors we have attempted to make CAM forms of these receptors by mutating two well-documented regions of GPCR constitutive activity. Initial experiments involving mutations in these areas have produced forms of the receptor either lacking robust constitutive activity or producing apparently null mutant forms of the receptor (5HT6). While these results have slowed progress on determining the inverse agonist activity of antipsychotic drugs on these receptors they open up interesting avenues of research on the variability in structure within the GPCR family and within 5HT receptors in particular. Therefore we propose to pursue three specific aims: 1) we will continue to test typical and atypical antipsychotic drugs at human CAM forms of the 5HT2A and 5HT2C receptors; 2) we will continue to mutate the human 5HT6 and 5HT7 receptors to produce CAM forms of these receptors and test antipsychotic drugs for inverse agonist activity at these receptors; 3) we will examine effects of constitutive activation on clozapine-sensitive 5HT receptor cellular trafficking, and the effects of inverse agonists on the trafficking of the mutated receptors. The results of these studies should reveal the role inverse agonist activity of antipsychotic drugs plays in the atypical properties of clozapine, and may indicate a major role for one or more of the clozapine-sensitive
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receptors in the atypical properties of clozapine. This information should be very helpful in designing a new generation of atypical antipsychotic drugs sharing clozapine's unique antipsychotic properties, but lacking its deleterious hematological effects. Information concerning alterations in cellular processing of CAM receptors should also be forthcoming, including information on the molecular domains involved in directing cellular compartmentalization, believed to play a key role in cellular receptor sensitivity states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTICO-THALAMIC SCHIZOPHRENIA
GLUTAMATE/GABA
MRNA
IN
Principal Investigator & Institution: Haroutunian, Vahram; Associate Professor; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Glutamatergic/GABAergic system abnormalities in the cerebral cortex and morphological/anatomical/biochemical abnormalities in the thalamus are present in schizophrenia. Some of the evidence comes from studies conducted in our laboratories showing changes in the expression of mRNAs encoding for ionotropic glutamate receptor genes in both the thalamus and the cortex, and for the GABA synthesizing enzyme glutamic acid decarboxylase (GAD-65 and GAD-67). Studies on the same brain specimens derived from extremely well characterized neuropsychiatrically and neuropathologically assessed schizophrenic subjects has shown that GAD mRNA level changes are reflected in functional abnormalities in the activity of GAD. The studies proposed aim to determine whether glutamatergic/GABAergic abnormalities in the neocortex are associated with glutamatergic/GABAergic abnormalities in the thalamus. Brain tissue specimens will be derived from: Dorsolateral prefrontal cortex (DLPFC) and the mediodorsal nucleus (MDN) of the thalamus; Cingulate cortex and the anterior group of thalamic nuclei; Precentral cortex (Brodmann 4/6) and the ventrolateral nuclear group of the thalamus; Inferior temporal gyrus (Brodmann 20) and the pulvinar; and Striate / Visual cortex (Brodmann 17) and the lateral geniculate nucleus of the thalamus. These specimens will be derived from 37 normal controls, 32 antemortem assessed and diagnosed schizophrenics who have been neuropathologically characterized to be free of any confounding neuropathological lesions, and 15 Alzheimer disease cases for comparative purposes. We will test hypotheses designed to determine whether glutamatergic and GABAergic abnormalities (mRNA and protein) in specific thalamic nuclei are associated with glutamatergic and GABAergic abnormalities in specific cortical regions and vice versa. In addition, studies in rats will test the hypothesis that the glutamatergic and GABAergic abnormalities in the prefrontal cortex are a direct result of lesions in the MDN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF D3 ANTAGONISTS TO TREAT COCAINE ADDICTION Principal Investigator & Institution: Mach, Robert H.; Professor; Radiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 30-JUN-2004
20
Haloperidol
Summary: (Applicant's Abstract) The goal of the research described in this application is to develop therapeutic agents that can be used to treat cocaine addiction. The strategy taken will be to synthesize and pharmacologically evaluate antagonists that are selective for the dopamine D3 receptor. The D3 receptor was chosen as the molecular target for drug development because of recent reports demonstrating that the behavioral and reinforcing effects of cocaine, an indirect dopamine agonist, are mediated through the activation of this receptor. Antagonists of the D2 class of receptors have not demonstrated great success in treating cocaine addiction because of their tendency to cause adverse motoric side effects. The failure of this approach can be attributed to the use of dopamine receptor antagonists such as haloperidol that have a higher affinity for D2 versus D3 receptors. A D3 receptor antagonist having a low affinity for D2 receptors is likely to succeed since this binding profile will result in a high blockade of mesolimbic D3 receptors (attenuating cocaine reinforcement) and a low occupancy of D2 receptors (resulting in a low tendency to cause extra pyramidal side effects). However, there is currently a shortage of D3-selective antagonists having a suitable D3 versus D2 receptor affinity to test this hypothesis. An additional incentive for focusing on D3 receptors as our target for drug development stems from our recent identification of a series of D3selective compounds, which are suitable lead compounds for further structure-activity relationship studies. Functional assays have determined that these compounds are antagonists of the D-class of receptors. The goal of this project is to improve both the D3 binding affinity and the selectivity of our lead compounds for D3 versus D2 receptors. Once a suitable compound is identified, the corresponding iodine-125 labeled analogue will be prepared and in vitro binding studies (Scatchard analyses, kinetic studies) of the D3 receptor will be conducted. The results of this research will produce D3-selective antagonists that have the potential for treating cocaine abuse. In addition, this research will result in the development of radiolabeled probes for studying both the function of D3 receptors in the CNS and the alteration in D3 receptor density thatoccurs as a consequence of cocaine abuse. 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 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
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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 D2 AND ADENOSINE A2A ROLES:TREMULOUS MOVEMENTS Principal Investigator & Institution: Salamone, John D.; Professor; Psychology; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, Ct 06269 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Symptoms of parkinsonism, such as akinesia, bradykinesia, and tremor, can be caused by degeneration of dopamine (DA) neurons, or by administration of DA antagonist drugs. Parkinsonism is characterized by a cascade of neurochemical events that reflect interactions between several neurotransmitters in the circuitry of the basal ganglia, including DA, acetylcholine, serotonin, GABA and adenosine. Within the last few years, increasing evidence has accumulated indicating that central adenosine neurons play an important role in modulating the functional circuitry of the basal ganglia. Several subtypes of adenosine receptors are involved in motor function, and anatomical studies have demonstrated that the adensonine A2A receptor subtype has a relatively high degree of expression within the striatum. Although several types of striatal cells contain some adensonine A2A receptors, these receptors are present in very high densities on striatopallidal neurons, which also tend to co-express DA D2 receptors and enkephalin. It has been suggested that antagonists of adenosine A2A receptors could have some potential utility as antiparkinsonian drugs. In a recent study from our laboratory, it was demonstrated that IP injections of the adenosine A2A antagonist, KF17837, also suppressed haloperidol-induced tremulous jaw movements, and reversed the locomotor suppression induced by this D2 antagonist. This profile of activity is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects in animal models. The proposed experiments are designed to investigate the role of the striatopallidal GABAergic pathway as a possible mediator of the putative antiparkinsonian effects of adenosine A2A antagonists. These proposed studies will focus on the tremulous jaw movement model, which is related to parkinsonian tremor. It is hypothesized that adenosine A2A antagonists are acting on striatopallidal GABAergic neurons that also express DA D2 receptors. In view of research showing that haloperidol increases extracellular GABA in globus pallidus, and that haloperidol-induced tremulous jaw movements are reduced by pallidal injections of bicuculline, it is hypothesized that doses of adenosine A2A antagonists that reduce jaw movement activity also will reduce haloperidol-induced increases in GABA release in globus pallidus. In addition, it is hypothesized that adenosine agonists and antagonists will interact to regulate the behavioral and
22
Haloperidol
neurochemical effects of haloperidol. These hypotheses will be investigated using studies that involve both systemic and intrastriatal injections of drugs that act upon A2A receptors, and the proposed work will involve a combination of behavioral pharmacology and microdialysis methods. This research is designed to enhance our understanding of the neurotransmitter interactions that are involved in the generation of tremulous movements, and to foster the development of new drugs for the treatment of parkinsonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINERGIC MECHANISMS OF INTERVAL TIMING & DRUG ABUSE Principal Investigator & Institution: Buhusi, Catalin V.; Assistant Professor; Psychology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 30-APR-2003 Summary: (provided by applicant): The main goal of this proposal is to evaluate the impact of the characteristics of conditioned stimuli on the effects of abuse drugs in the context of a class of behaviors that was shown to accurately reflect the degree of intoxication: timing in the seconds-to-minutes range. While fundamental behavioral processes such as learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals, drugs of abuse result in distortions of time perception. Dopamine (DA) agonists (e.g., methamphetamine, AMP) result in behavior consistent with a speeding up of the internal clock, while DA antagonists (e.g., haloperidol, HAL) result in behavior consistent with a slowing of the clock. While there is the possibility that some reinforcing and addiction properties of DA agonists might be related to their effects on the internal clock, evidence suggests that DA might also serve attentional or predictive functions. It is therefore possible that besides clock-related effects, DA drugs might distort time perception indirectly by affecting the filtering or prediction of events. The experiments described in this proposal aim at dissociating the memory effects, clock-effects, and attentional effects of DA drugs on interval timing in the rat animal model, because DA neuropsychopharmacology is very similar in rats and humans. The main goals of the project are as follows: (1) To develop a set of procedures to evaluate the impact of the characteristics of conditioned stimuli on timing and memory for timing. By contrasting the timing of "empty" and "filled" intervals one can dissociate attentional from clock and memory effects. The modality bias will be examined by using auditory or visual timed cues. (2) To dissociate the attentional and clock effects of AMP and HAL by evaluating their effect on timing "empty" and "filled" intervals in rats. There are no studies of the effects of DA drugs on timing "empty" intervals. Dose response curves will be established for both AMP and HAL (three drug doses for each drug). (3) To dissociate the clock and attentional effects of AMP and HAL on interval timing, by studying the interruption of the timed interval by another event (gap). The experiments will dissociate the clock (shift left/right) and attentional (reset/stop) effects of AMP and HAL. There are no studies of the effects of DA drugs on memory for timing "empty" intervals or intervals with gaps. Together, the studies will inform current models of timing, time perception, and DA psychopharmacology. They will help elucidate the pharmacological basis of interval timing and understand the impact of the characteristics of the attentional cues on the distortions of time perception by drugs of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYSFUNCTION SCHIZOPHRENIA
OF
DLPFC
PYRAMIDAL
Studies
23
NEURONS
IN
Principal Investigator & Institution: Lewis, David A.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 30-JUN-2008 Summary: The central hypothesis of our Center focuses on critical disturbances in the regulation of cognition and behavior in schizophrenia that reflect functional abnormalities in the intrinsic circuitry of the dorsolateral prefrontal cortex (DLPFC) and in its interconnections with other brain regions. These functional disturbances are hypothesized to arise during posnatal development as a consequence of alterations in the molecular signals and structural elements that determine synaptic efficacy in the affected neural circuits. These alterations include somatodendritic morphological abnormalities, such as smaller somal volumes, decreased dendritic arbor size and complexity, and reduced dendritic spine density, of pyramidal neurons, the principal excitatory projection neurons of the neocortex. Furthermore, these somatodendritic abnormalities in schizophrenia may be specific to, or at least present to a greater degree in, a subset of pyramidal neurons. Because a neuron' s dendritic arbor is a maj or determinant of its functional circuit properties, pyramidal neuron somatodendritic abnormalities, in concert with related synaptic disturbances, may be central to DLPFCmediated cognitive dysfunction in schizophrenia. Consequently, knowledge of the specific subsets of pyramidal neurons that are affected in schizophrenia is essential for determining both the potential causes of these abnormalities and their contributions to disturbed DLPFC information processing. Thus, using an integration of experiments in postmortem human brain specimens and in nonhuman primates, the studies proposed in this project are designed to determine 1) the laminar location(s) of the DLPFC pyramidal neurons that exhibit somatodendritic abnormalities in schizophrenia; 2) the molecular phenotypes of pyramidal neurons that furnish different types of extrinsic projections in monkey DLPFC; 3) the somatodendritic integrity of molecularly-identified subpopulations of DLPFC pyramidal neurons in schizophrenia; and 4) the molecular mechanisms that may contribute to developmental somatodendritic changes in monkey DLFPC pyramidal neurons. These investigations have a number of conceptual and technical links with other Center projects and depend upon support provided by all of the proposed cores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATYPICALS
EFFECTIVENESS
OF
SWITCHING:
CONVENTIONALS
TO
Principal Investigator & Institution: Essock, Susan M.; Professor and Director; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: Effectiveness of Switching: Conventionals to Atypicals Over the past several years, new, so-called "atypical," antipsychotic medications have become available to treat schizophrenia. Olanzapine and risperidone are the two most widely prescribed antipsychotics; together they account for over 40 percent of all antipsychotic prescriptions. Given their wide usage, we know surprisingly little about the effectiveness of these newer medications in routine practice settings. Despite a decade of availability of atypical antipsychotics, about 40 percent of the antipsychotic prescriptions filled in the United States today are still for conventional agents. Given
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Haloperidol
that the atypical antipsychotics may be more effective than the conventional ones and have less burdensome side effects, should people who are relatively stable on the older medications but who are still symptomatic or troubled by medication side effects be switched to an atypical medication? What are the benefits and risks associated with such medication switches? A total of 300 consenting patients with schizophrenia from a large, diverse public mental health system, who are living in the community and taking conventional antipsychotic medications but who are still troubled by symptoms or medication side effects, will be randomly assigned to stay on their current conventional antipsychotic medication (N =100) or to switch to olanzapine (N =100) or risperidone (N=100). This design specifically controls for process of changing medications because one group continues on current treatment. The proposed study, therefore, will assess what incremental risks and benefits can be expected from switching from a conventional to a first-line atypical antipsychotic agent. All medications will be open label, and treatment will be by the study participants' routine providers. Study participants will be asked to stay in their assigned treatment condition for 6 months, after which time medication decisions will be up to the patient and the prescribing psychiatrist. Study participants will be interviewed with quantitative instruments at baseline and at followup intervals for 1 year to determine clinical course and the types of services used. The study will determine the incremental risks and benefits of switching from a conventional to the most commonly prescribed atypical antipsychotics, and the relative risks and benefits of switching to olanzapine versus switching to risperidone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL MRI OF TEMPORAL INFORMATION PROCESSING Principal Investigator & Institution: Rao, Stephen M.; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002 Summary: The capacity to precisely time events is important for a variety of human activities. Several decades of research in animals and humans have advanced our knowledge of interval timekeeping mechanisms, so that now there is broad support for the view that some aspects of time are explicitly represented in the ventral nervous system. Despite this advancement, our knowledge of the neural systems supporting temporal cognition remains limited. It is the intent of this project, therefore, to use whole-brain fMRI to gain a comprehensive understanding of the brain systems that support temporal information processing. The proposed project consists of three aims. The first aim will identify the functional neuroanatomy of an internalized timekeeping system operating across millisecond and second intervals using a time bisection task. A separate experiment will determine the neural systems supporting working memory (WM) components of temporal information processing by conducting fMR scanning during the delay period of a temporal comparison task. The second aim will examine the role of dopaminergic and cholinergic systems in timekeeping and working memory aspects of interval timing. Two double-blind, placebo-controlled, crossover timekeeping and working memory aspects of interval timing. Two double-bind, placebo-controlled, crossover experiments will be conducted involving administration of methylphenidate, haloperidol, physostigmine, and scopolamine to health subjects performing time bisection and temporal WM tasks while undergoing fMR scanning. The third aim will identify the nature of the interval timing deficits associated with basal ganglia dysfunction. This will be accomplished by conducting fMR imaging in unmedicated patients with Parkinson's disease (PD) and health elderly control subjects during the performance of perceptual and motor timing tasks. In an additional experiment, the
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effects of dopamine replacement on perceptual and motor timing tasks will be examined in a crossover drug trial involving PD patients on and off medication. The three aims of this project are designed to address fundamental cognitive neuroscience questions involving temporal information processing. The above experiments will also have clinical implications for a variety of neuropsychiatric disorders with established or presumed deficits in timing, including schizophrenia, Parkinson's and Huntington's disease, and Attention Deficit Hyperactivity Disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENDER AND SEX HORMONES AND OPIOID ANALGESIA Principal Investigator & Institution: Levine, Jon D.; Professor; Oral and Maxillofacial Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-JAN-2007 Summary: Despite considerable research on gender differences in pain sensitivity, sex differences in pain modulation by opioid analgesics in humans have only recently been examined. We showed, in postoperative dental patients, that k (kappa)-partial agonist opioids produce significantly greater analgesia in females than in males. This finding was observed with three different opioid analgesics that are k-partial agonists: pentazocine, nalbuphine and butorphanol. In dose response studies performed during the current grant period, we further demonstrated that the greater analgesic potency in females for k- partial agonists may be at least partly due to the existence of a naloxonesensitive anti-analgesia mechanism that predominates in males. Whereas due to this anti-analgesia a k-opioid (nalbuphine) produced greater pain than placebo in males, the addition of naloxone resulted in a markedly enhanced and prolonged analgesia in both genders. Recent evidence in animal models suggests that k-partial agonists may inhibit analgesia by their action at naloxone-sensitive s (sigma)-receptors, which could explain the anti-analgesic effects of k-opioid partial agonists. In previous experiments, we found that combining k- partial agonists with the alpha2-adrenergic agent, clonidine also enhances analgesia. The proposed experiments will identify the mechanism of the antianalgesic action of the k-partial agonists. They will also determine optimal doses for the specific k-partial agonist (nalbuphine, butorphanol, pentazocine) naloxone combinations in other clinical settings, including repeated use in hospitalized post-surgical patients and patients with neuropathic pain. We will also explore gender and ethnic differences in analgesic responses resulting from k-opioids combined with the adjuvants known to interact with other neurotransmitter systems/mechanisms involved in pain modulation, that is, agents that act at a2- adrenergic receptors, and s-receptors. Finally, we will further characterize the opioid contribution to placebo analgesia. These studies will provide much-needed knowledge of gender differences in responses to opioid analgesics and should lead to gender- specific recommendations for more effective, better targeted pain therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION AND DRUG-INDUCED SENSITIVITY TO ALCOHOL Principal Investigator & Institution: Radcliffe, Richard A.; Assistant Professor; Pharmacology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2005
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Haloperidol
Summary: (provided by applicant): Behavioral sensitivity to alcohol can be modified as a function of both environmental and genetic factors. The underlying basis of this effect is the ability of neurons to adapt in response to environmental perturbations including, but not limited to alcohol exposure, and the specific nature of this response is dependent on genetic makeup. These processes may be an important feature in the etiology of alcoholism. Evidence indicates that drugs acting on dopamine (DA) neurons are able to alter the behavioral response to alcohol in rodents. Thus, 24 hrs after a single treatment with the DA antagonist haloperidol or the indirect DA agonist methamphetamine, rats become more or less sensitive to alcohol, respectively, and "rapid" tolerance develops one day after a single dose of alcohol. These acute drug responses will be exploited to investigate the global gene expression changes occurring in DA pathways that contribute to altered alcohol sensitivity. Specific Aim 1 will fully characterize the behavioral response to alcohol (loss of righting reflex) 24 hrs after acute treatment with haloperidol, alcohol, or methamphetamine in replicate inbred High and Low Alcohol Sensitive rat strains. Gene expression analyses will be performed in Specific Aim 2. Rats will be sacrificed at 8 hrs following administration of a single optimal dose of each drug and the striatum and ventral midbrain will be dissected. RNA will be extracted from these structures and gene expression will be determined with the use of the Affymetrix GeneChip system. This will provide a total of 16 experimental conditions comprised of different drug/genotype combinations. It is postulated that each of these conditions will show different, but overlapping gene expression profiles. The genes that are important in the altered alcohol response will be identified by clustering and discriminative analysis procedures in a comparison of the expression profiles and the behavioral responses among the 16 conditions. Specific Aim 3 will validate important gene expression changes with the use of ribonuclease protection assays and/or real-time quantitative PCR. The results of the proposed studies will offer insight into the neuroadaptive processes that contribute to alcohol abuse and will also provide more information from which to further investigate alcohol related neuroadaptation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC AND BEHAVIORAL DISSECTION OF INHIBITORY CONTROL Principal Investigator & Institution: Zhuang, Xiaoxi; Neurobiology/Pharmacology/Phys; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2004; Project Start 03-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Lack of inhibitory control over apparently voluntary motor acts is a behavioral symptom found in attention deficit hyperactivity disorder, drug addiction, Tourette's Syndrome, and obsessive-compulsive disorder. It is highly debated whether impaired inhibitory control is due to hyper- or hypo-dopaminergic activity. To investigate its neurobiological basis, we have generated "hyperdopaminergic" transgenic mice by reducing the dopamine transporter expression (DAT knockdown). Our preliminary studies suggest that DAT knockdown mice model aspects of impaired inhibitory control and that impaired postsynaptic dopamine D2 receptor function may underlie such behavioral deficits. Aim 1 of the proposed studies is to determine the specific biochemical changes underlying impaired inhibitory control in DAT knockdown mice. We will first identify the behavioral mechanisms underlying impaired inhibitory control in DAT knockdown mice: whether it's delay aversion or response inhibition, two processes implicated as core behavioral deficits in impaired inhibitory control. We will then investigate what signaling molecule is responsible for
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the impaired postsynaptic D2 receptor function in DAT knockdown mice: receptor, G protein, receptor-G protein coupling or adenytyl cyclase activity. We will take both behavioral measures and biochemical measures from each animal and examine the degree of association between them. Aim 2 is to test the hypothesis that impaired postsynaptic D2 receptor function underlies impaired inhibitory control using a pharmacological rescue approach. Our preliminary studies suggest that chronic D2 antagonist treatment is able to reverse behavioral deficits in DAT knockdown mice. We will analyze D2 signaling and behavioral changes in DAT knockdown mice after chronic treatment with D2 antagonists. We will test the hypothesis that such treatment will reverse D2 signaling and behavioral deficits in DAT knockdown mice. Aim 3 is to test directly the hypothesis that impaired D2 receptor function underlies impaired inhibitory control using mice that lack or have reduced postsynaptic D2 receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HALOPERIDOL, OLANZAPINE & RISPERIDONE IN CHILDREN W/ PSYCHOTIC DISORD Principal Investigator & Institution: Lieberman, Jeffrey J.; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIPPOCAMPAL RECURRENT INHIBITION AND N-ACETYL ASPARTYL GLUTAMATE Principal Investigator & Institution: Greene, Robert W.; Research Health Scientist; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: The behavioral abnormalities associated with schizophrenia are likely to involve pathological function of the limbic system. Functional and structural neuroimaging studies in the limbic region of schizophrenic brains have provided compelling evidence in support of this assertion. Ingestion of phencyclidine (PCP) or systemic injection of ketamine produces a syndrome that mimics the symptoms of acute schizophrenic psychosis. These pharmacological observations raise the possibility that a decrease of normal NMDA receptor (NMDAR) function can elicit psychotic symptoms similar to those suffered by schizophrenic patients. Recently, Mohn, et al (1999) describe a transgenic mouse model of schizophrenia, a partial knock out of the NR1 subunit of the NMDAR (5% expression), with behavioral deficits such as increased motor activity, stereotype and deficits in social and sexual interactions. This partial "knock down" of NR1 expression is rescued by haloperidol and clozapine. However, the mechanism(s) of action of decreased NMDA- receptor function that result in the observed deficits in information processing integral to the syndrome of psychosis have been little investigated. Our findings have lead to the following hypotheses: the psychotogenic action of NMDA antagonists may be attributed to selective blockade of the NMDAdependent drive of inhibitory circuits (Grunze). The decreased excitatory drive of interneurons disrupts network function so that abnormal information processing consistent with cognitive deficits associated with psychosis, ensues. In particular, [Specific Aim I] it is hypothesized that the EPSP of CAL interneurons has a significant NMDA-dependent component that is larger than the NMDA component of the feedforward Schaffer collateral input to CA1 pyramidal neurons, and/or EPSC is more
28
Haloperidol
sensitive to NMDA antagonists. Accordingly, NMDAR antagonists have a selectively greater effect on the EPSP's of interneurons (in the CA1 region of the hippocampus the EPSP's and EPSC's that we will test, original from either feed-forward-CA3-or feedbackward-CA1-input or from both) compared EPSC's of projection cells. Pathological NMDAR hypofunction could result from multiple mechanisms, including but not limited to 1) factors affecting NMDAR- binding to glutamate; 2) factors affecting NMDAR-associated channel activity; 3) factors affecting downstream mechanisms associated with NMDAR activation (for example those linked to the NMDA-associated PSD-complex). We plan to examine the first of these mechanisms. We [Specific Aim 4a] hypothesize that an endogenous compound, N-acetyl- aspartylglutamate (NAAG), has NMDAR antagonist activity and can selectively block the NMDAR-component of EPSC's on interneurons in the CA1 region of the hippocampus. We further [Specific Aim 4b] hypothesize that the turnover of NAAG is sufficiently high that inhibition of NAAG's catabolic enzyme will block the NMDAR-component of EPSC's and exposure to a soluble form of these catabolic enzyme [Specific Aim 4c] will enhance the NMDARcomponent by decreasing endogenous NAAG. Our preliminary data demonstrates that inhibition of GCP II increases endogenous NAAG sufficient to significantly reduces NMDAR synaptic activation in CA1 pyramidal cells and interneurons in the hippocampal slice, probably as a result of the high rate of turnover of NAAG in vitro. The effects on NMDAR activity of a knockout of the GCP III gene are hard to predict in part because: 1) the mechanisms responsible for the rate of production of the NAAG mediating this response are unknown; 2) NMDAR activity in response to a chronic increase in NAAG is unknown. Nevertheless, a state of chronic NMDAR hypofunction is a distinct possibility that, in consideration of its association with psychosis ought to be examined as a first step towards the phenotypic characterization of these animals. We [Specific Aim 5] hypothesize that NMDAR function will be reduced in the CA1 region of the hippocampi of GCP II knockout mice compared to wild type mice. If true, thee ko mice may serve in behavioral studies of NMDAR hypofunction in the development and maintenance of place (or other specific associations) hippocampal cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN COCAINE DISCRIMINATION Principal Investigator & Institution: Rush, Craig R.; Associate Professor of Psychiatry; Behavioral Science; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 01-MAR-1997; Project End 30-JUN-2007 Summary: (provided by applicant): The present application is a request for continued funding of a project entitled "Cocaine Discrimination in Humans: Pharmacological Specificity" (DA010325). Recent data indicate that nearly 2 million Americans used cocaine in the past month. Alarmingly, between 1991 and 2001 the number of 8th, 10th, and 12th graders that reported using cocaine in the past 30 days increased 140, 86, and 50 percent, respectively. Thus, cocaine abuse continues to represent a significant public health concern, and will likely remain a problem for the foreseeable future. Intensive research efforts have been aimed at elucidating the neuropharmacological mechanisms that mediate the effects of cocaine. Drug-discrimination studies with laboratory animals that used the substitution and pretreatment methodologies have implicated a prominent role of dopamine in mediating the effects of cocaine. During the initial funding period of this project we used a drug discrimination task and the substitution methodology to demonstrate that dopamine systems are involved in mediating the discriminativestimulus effects of cocaine in humans. We are not aware of any published studies in which the discriminative-stimulus effects of cocaine were assessed in humans following
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pretreatment with another drug even though drug-discrimination procedures may be particularly well suited for studying agonist-antagonist interactions. The aim of this application is to further characterize the role of dopamine in mediating the discriminative-stimulus effects of cocaine in humans using a pretreatment methodology. To accomplish this aim, 3 laboratory experiments will be conducted with volunteers with histories of cocaine abuse. The discriminative-stimulus and subjective effects of cocaine will be assessed alone and following pretreatment with mazindol, a dopamine uptake blocker (Exp. 1); fluphenazine, a D1-D2 dopamine receptor antagonist (Exp. 2); and haloperidol, a D2 dopamine receptor antagonist (Exp. 3). We predict that pretreating volunteers with a dopamine agonist or antagonist will shift the cocaine doseresponse curve, leftward and rightward, respectively. The experiments proposed in this "proof-of-concept" continuation application will provide additional information concerning the role of dopamine in mediating the discriminative-stimulus effects of cocaine in humans. Elucidating the role of dopamine in mediating the effects of cocaine may guide the development of pharmacological interventions for cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE TOLERANCE; SIGMA RECEPTOR AS A THERAPEUTIC TARGET Principal Investigator & Institution: Ganapathy, Vadivel; Professor; Biochem and Molecular Biology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The goal of this project is to gather evidence in support of a novel strategy for the induction of immune tolerance, namely to use sigma 1 receptor as a potential therapeutic target. Sigma 1 receptor is defined as a specific binding site for various psychoactive drugs such as haloperidol and pentazocine. This receptor has been recently cloned and characterized. It is a membrane-bound protein found primarily in intracellular sites. It is expressed in various tissues including immune cells and placenta. There is compelling evidence for an immunosuppressive role of sigma 1 receptor-specific ligands. The role of this receptor in immune function has received increasing attention in recent years as it has become apparent that progesterone is a putative endogenous ligand for this receptor. The goal of this project is to delineate the molecular events involved in the immunosuppressive function of sigma 1 receptor and to investigate the possible role of progesterone in the maintenance of maternal tolerance toward placental allograft. This project will test the following hypotheses: 1) Progesterone and several pharmacological ligands suppress the function and proliferation of T lymphocytes by acting as specific ligands for the sigma 1 receptor; 2) sigma 1 receptor produces its effects by influencing the function of other cellular proteins in T lymphocytes and placenta via protein-protein interaction; 3) Abolition of sigma 1 receptor gene expression by targeted disruption of the gene in a mouse model will lead to maternal intolerance of the placental allograft. Three specific aims are proposed to test these hypotheses. Specific Aim 1 is to study the expression of sigma 1 receptor in quiescent and activated T lymphocytes and to establish the role of this receptor in the suppression of T cell function. This will be done by analyzing the expression of sigma 1 receptor at the molecular and functional level in T lymphocytes before and after activation. The obligatory role of sigma 1 receptor in T cell function will be evaluated by analyzing the biological effects of sigma 1 receptor-specific ligands in sigma 1 receptor-positive (control) and sigma 1 receptor-negative (stable transfectants expressing antisense sigma 1 receptor mRNA) Jurkat cells. Specific Aim 2 is to identify the proteins in human placenta and in T lymphocytes that interact with sigma 1 receptor
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Haloperidol
using the yeast two-hybrid system. Identification of the target proteins that interact with sigma 1 receptor will help to unravel the molecular mechanisms of cell signaling mediated by sigma 1 receptor. Specific Aim 3 is to determine, using sigma 1 receptor knockout mice, whether the absence of the receptor manifests itself as embryo lethality, an inability of the embryo to defend itself against maternal immune system, or as an inability of the maternal immune system to maintain tolerance toward the placental allograft. This project may have significant physiological, clinical, and therapeutic relevance. The proposed studies may lead to a better understanding of the induction of maternal tolerance toward placental allograft and may provide the basis for future efforts to examine the therapeutic potential of sigma 1 receptor-specific ligands as effective immunosuppressants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MARKERS SCHIZOPHRENIA
OF
OLFACTORY
NEUROTRANSMISSION
IN
Principal Investigator & Institution: Rioux, Lise; Neurobiology and Anatomy; Drexel University College of Medicine 245 N 15Th St Philadelphia, Pa 19102 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Reduced expression of synaptic and plasticityrelated proteins in OB in schizophrenia suggests alterations in the synaptic machinery. Dysfunctional synapses between ORNs and target cells during development and throughout life may be responsible for the reduced OB volume and the olfactory deficits observed in schizophrenia. Understanding the mechanisms and consequences of this dysfunction is essential to the development of better treatment for schizophrenia. It is our hypothesis that in schizophrenia, synapses of the ORNs with their OB targets are hypofunctional. Hypoglutamatergic transmission at these synapses results in an impairment of long-term potentiation in the OB. While preliminary results suggest that this hypothesis is valid, it warrants further study. In aim 1, we will show evidence of hypoglutamatergic transmission at the synapses between ORNs and their OB targets in schizophrenia. These synapses are located in discreet spherical composites of pre- and post-synaptic elements called glomeruli. We will use quantitative radioimmunohistochemistry to test the hypothesis that there is a decreased expression of some subtypes of NMDA, AMPA or Group1 metabotropic glutamate receptors in OB glomeruli from individual with schizophrenia. We will also use a novel proteomic method, immunodetection amplified with T7 polymerase (IDAT) to investigate a shift in subunit composition away from NMDAR2 B subtype and toward gluR2 subtype. We expect glutamate receptors, in particular the NMDA receptors, to be down regulated in OB glomeruli in schizophrenia. Glutamatergic function is essential to the induction and maintenance of LTP. Several proteins, including syntaxin, brain-derived neurotrophic factor (BDNF), nitric oxyde synthetase (NOS) and activity-regulated cytoskeletonassociated protein (arc) are up-regulated following the induction of LTP and can serve as markers for that form of synaptic plasticity. We will look at the expression of these selected LTP markers in OB glomeruli with quantitative radioimmunohistochemistry. We will also use IDAT to examine the coordinate expression of glutamate receptors and LTP markers in the same glomeruli. We expect LTP markers to be down regulated in glomeruli in schizophrenia. We also expect a correlation between the expression of NMDA receptors and LTP markers. A correlation between glutamatergic function, LTP markers and schizophrenia will better define the role of these proteins in the olfactory deficits observed in schizophrenia. The effect of the antipsychotic on the expression of
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these proteins will also be investigated in mice chronically treated with haloperidol to discriminate between disease- and treatment related changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ABNORMAL EXCRETION IN SCHIZOPHRENIA Principal Investigator & Institution: Goldman, Morris B.; Director; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METABOLISM HALOPERIDOL AGENTS
BASED
DRUG
DESIGN--EVALUATION
OF
Principal Investigator & Institution: Ablordeppey, Seth Y.; Director and Professor of Medicinal Chem; Florida Agricultural and Mechanical Univ 400 Foote Hilyer Administration Center Tallahassee, Fl 32307 Timing: Fiscal Year 2002 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODELING ANTIPSYCHOTIC-INDUCED WEIGHT GAIN IN RATS Principal Investigator & Institution: Fernstrom, John D.; Associate Prof of Neuroendocrinology; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 24-DEC-2003; Project End 30-NOV-2005 Summary: (provided by applicant): This revised Exploratory/Developmental grant application seeks funding through an NIMH R21mechanism (PA- 00-073) to conduct exploratory experiments to determine if the chronic delivery to rat, of antipsychotic drugs by constant infusion, to achieve sustained, therapeutic plasma concentrations (for humans) will (a) cause body weight gain (primary aim), and/or (b) modify neuropeptide neurons in hypothalamic appetite control circuitry suggestive of appetite stimulation (secondary aim). Antipsychotic drugs cause significant weight gain in schizophrenic humans, but in almost all cases examined to date, not in rats. This surprising species dichotomy may be due to the manner used to deliver antipsychotics to rats, chronically (single, daily injections) and the more rapid metabolic rate in rats than in humans, such that rats are exposed only a few hours each day to therapeutic plasma drug levels. In this project, adult male and female rats will be implanted with Osmette minipumps to deliver a constant infusion of each of several antipsychotic drugs (haloperidol, clozapine, olanzapine, risperidone, sulpiride, ziprasidone) for 28 days. Food intake, body weight, and blood and brain drug levels will be monitored. Drug dose will be adjusted to set plasma concentrations in the clinically effective range to optimize the chance of observing weight gain. This paradigm will then be used to explore for changes, using in situ mRNA analysis, in the activity of neuropeptide neurons embedded in hypothalamic appetite control circuitry (arcuate neuropeptide-Y and proopiomelanocortin/alphaMSH, paraventricular corticotropin releasing hormone, and lateral hypothalamic orexin). The successful identification of an experimental paradigm in rats that cause, antipsychotics to induce weight gain would allow its application to the study of the underlying mechanisms causing this unwanted side-
32
Haloperidol
effect, and could then be applied to the development of adjunct or new treatments that would minimize weight gain, while maintaining antipsychotic efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NALTREXONE BLOCKADE OF NMDA Principal Investigator & Institution: Krystal, John H.; Kent Professor and Deputy Chair for Rese; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-JUL-2003 Summary: (Adapted from the Investigator's Abstract) The capacity of ethanol to block N-methyl-D-aspartate (NMDA) glutamate receptors contributes to its behavioral effects in animals and humans. Recent preclinical data indicate that NMDA receptors and u opiate receptors are co-localized and have opposing actions in several brain regions involved in reward, such as the nucleus accumbens, the amygdala, and the raphe nucleus. These finds lead to the prediction that the mu receptor antagonist, naltrexone, would block the rewarding effects of NMDA antagonists, such as ketamine and ethanol. The capacity of naltrexone to attenuate the rewarding effects of ethanol contributes to its capacity to prevent episodes of drinking from becoming relapses to alcohol abuse. Similarly, our pilot data suggest that naltrexone reduces the euphoric and ethanol-like effects of subperceptual doses of ketamine. However, the mechanisms underlying the interactions of ethanol and naltrexone are not well understood. It is timely to explore the interactions of human opiate and glutamate receptor systems. Acamprostate, another promising pharmacotherapy for alcoholism, may act, in part, via glutamate receptor systems. The NIAAA multicenter study, Project COMBINE, will test the interactive effects of naltrexone and acamprostate. Better understanding of the interactions of opiate and glutamate systems may provide insights into findings from this study. In this application, we test the hypothesis that naltrexone attenuates the euphoric and ethanollike effects of the NMDA antagonist, ketamine. We propose to examine the interactive effects of naltrexone and ketamine in 36 healthy human subjects using a randomized, balanced, placebo-controlled, within subjects design. The primary outcome measures include the visual analog scale measuring similarity to ethanol and the visual analog scale measuring "high." In our previous studies, we found that the rewarding effects of ketamine were remarkably resistant to antagonism by pretreatment with haloperidol or facilitation by pretreatment with lorazepam or amphetamine. We hypothesize that ketamine may mimic some aspects of the actions of ethanol at the NMDA receptor. Thus, the blockade of the rewarding effects of ketamine by naltrexone may provide insight into an important mechanism underlying the psychopharmacology of ethanol and the treatment of alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROANATOMY OF ANTIPSYCHOTIC DRUG ACTION Principal Investigator & Institution: Frankle, William G.; Psychiatry; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): The dopamine (DA) hypothesis of schizophrenia proposed that positive symptoms are associated with hyperactivity of DA transmission. This hypothesis was later refined by the proposition this DA hyperactivity was localized in the ventral striatum (VST) and the limbic regions of the medial temporal lobe. This was supported by the mesolimbic selectivity of atypical antipsychotic drugs,
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33
demonstrated in preclinical studies, and by imaging studies suggested that these drugs achieve higher D2 receptor occupancy in temporal limbic regions compared to striatum. On the other hand, brain imaging studies have recently demonstrated that schizophrenia is associated with increased presynaptic DA activity in the striatum. Furthermore, preliminary data obtained with high resolution PET suggest that schizophrenia is associated with excessive DA activity in the associative striatum (AST) rather than in the VST, and that AST DA hyperactivity is predictive of fast treatment response to antipsychotic drugs. These results suggest that D2 receptor blockade in the AST, rather than in the VST, might be critical for antipsychotic action. The general goal of this career development plan is to further evaluate this proposition, by determining D2 receptor occupancy in the VST, AST and sensorimotor striatum of the rat following administration of typical and atypical antipsychotic drugs, and to compare these regional occupancies to the degree of occupancy required to achieve a therapeutic response in patients with schizophrenia. In specific aim (SA) 1, microPET imaging studies will be combined with ex vivo binding studies to define the dose-occupancy relationship of 8 antipsychotic drugs (2 typical and 6 atypical). In SA2, imaging D2 receptors in striatal subregions and extrastriatal regions with the novel tracer [18F]fallypride will be developed in humans. In SA3, occupancy of D2 receptors achieved in these regions by theses drugs during treatment of schizophrenia will be measured with [18F]fallypride. Together, these data will permit testing the overarching hypothesis that, for both typical and atypical drugs, occupancy in the AST is required to achieve clinical response. The research plan will require the candidate to develop a sophisticated understanding of PET imaging and antipsychotic medication pharmacology, skills that will be essential in the candidate's development toward becoming an independent clinical investigator using PET. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROCHEMISTRY SCHIZOPHRENIA
OF
NICOTINE
DEPENDENCE
IN
Principal Investigator & Institution: Schiffer, Wynne K.; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 06-JAN-2003; Project End 05-JAN-2005 Summary: (provided by applicant): Nicotine abuse is three times more prevalent in schizophrenic over non-psychiatric populations. It has not been established whether this phenomenon is inherent to schizophrenia or an effect of chronic neuroleptic treatment. Nicotine related increases in brain dopamine are associated with its abuse. Schizophrenic patients or animals given NMDA antagonists to putatively model schizophrenia, express an enhanced dopamine response to stimulants. This response is similar in many respects to that exhibited by animals chronically treated with the neuroleptic, haloperidol. We suggest that the pathology associated with dysfunctional NMDA receptors enhances excitatory input to brain dopamine systems. While chronic antipsychotic therapy might reduce inhibitory control over dopamine. Although different in origin, these imbalances may result in a similar. Amplified, response to nicotine, It follows that the enhanced response to nicotine may be regulated by either decreasing excitatory or increasing inhibitory neurochemical activity, respective of the underlying pathophysiology. We propose to examine this hypothesis with micro PET imaging techniques and microdialysis to explore the effects of a nicotine challenge on brain dopamine in pharmacologically altered biologically states. By chronically treating rodents with the NMDA antagonist, PCP, haloperidol, or both, we intend to examine the effects of haloperidol in the absence or presence of disease on the response to
34
Haloperidol
nicotine. In separate groups, we propose to use additional drugs to reduce excitatory activity with the glutamate antagonist, topiramate. Or increase inhibitory activity with the GABA agonist, gamma-vinyl GABA, prior to the nicotine challenge. We hope to guide the development of novel therapies for dual-diagnosis schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPATHOLOGY SCHIZOPHRENIA
OF
DOPAMINE
SYSTEMS
IN
Principal Investigator & Institution: Roberts, Rosalinda C.; Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Schizophrenia is a devastating illness, with unknown pathophysiology, that affects 1% of the world's population. The experiments in the following revised proposal will focus on the basal ganglia and dopamine (DA) pathology in schizophrenia (SA1) and relate these changes to those occurring in rats treated with antipsychotic drugs (APDs) (SA2). Our preliminary data shows abnormalities in morphology of DAergic neurons in the substantia nigra (SN) and in the number of TH+ striatal synapses in electron microscopic (EM) studies of postmortem tissue from subjects with schizophrenia (SZ), similar structural changes and a decrease in number of TH+ cells in rats treated with APD. SA1 tests the hypothesis that the DA system is perturbed in the basal ganglia of SZ, using tissue from normal controls, SZ treated with typical or atypical APDs or off-drug. SA2 tests the hypothesis that anatomical changes observed in SN and ventral tegmental area (VTA) of SZ are the results, in part, of APDs, and will determine the contributing physiological mechanisms. In both aims, we will determine if the morphological alterations seen will show regional variations that are consistent with the differential effects of typical and atypical APDs on the activity of midbrain DA neurons. In this revision, we have modified the EM analysis of the SN and added 3 parallel experiments in both the human tissue and rats (treated with haloperidol or clozapine or controls). In SA1a the synaptic organization of DA labeled profiles will be analyzed in the human striatum at the EM level. In SA1b & SA2a, the number and size of Nissl stained, and TH+ cells double labeled with the DA transporter (DAT), or a selective marker of DA cells, SK3, will be determined using stereological methods in the SN/VTA. In SA1c & SA2b at the EM level, the integrity of subcellular organelles and the synaptic organization to the TH+ neurons (also labeled with DAT or SK3) will be studied. Using in situ hybridization SA1d & SA2e will determine if TH synthesis is affected at the level of transcription. SA1c & SA2d will determine if cytoskeletal proteins are upregulated. SA1f & SA2e will determine if the loss of TH in neurons is due to changes at the translational level by using Western blot analysis. SA2f will study the time course of the anatomical changes observed during APD treatment and relate these changes to the development of depolarization (DP) block. SA2g tests the hypothesis that morphological alterations in SN/VTA neurons will not occur in rats treated with APD if DP block is prevented (with a unilateral striatal lesion). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROTENSIN AND ETHANOL QTLS IN RATS Principal Investigator & Institution: Erwin, V G.; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 23-SEP-1998; Project End 30-JUN-2004
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35
Summary: (Adapted from the Investigator's Abstract) Identification of genes and associated neurochemical processes that mediate differences in ethanol sensitivity and acute tolerance will assist in understanding mechanisms underlying alcohol abuse and alcoholism. The proposed research will further test the hypothesis that individual differences in innate sensitivity to ethanol are governed by differences in neurotensin (NT) levels and receptor densities in specific brain regions. These studies will utilize quantitative genetic strategies coupled with pharmacological, biochemical and behavioral approaches. Specific aims include investigations to determine the effects of altering NT levels on ethanol sensitivity in rats (HAS and LAS) selectively bred for differences in duration of ethanol-induced loss of righting response or sleep time. Two measures of sensitivity will be used, blood ethanol concentrations at regaining righting response (BECST) and BEC at regaining performance on a rotorod (BEC1RR). Various doses of haloperidol (0.5 to 2.0 mg/Kg) will be administered 16 to 20 hours before ethanol to produce dose-dependent changes in NT levels and ethanol responses. Also, the ability of the NT receptor antagonist, SR 48692, to block ethanol responses will be determined in control and haloperidol-treated HAS and LAS rats. Other aims of this proposal are to identify chromosomal locations, by quantitative trait loci analyses, of genes that regulate brain NT levels and receptor densities and to determine common QTLs for NT measures and measures of ethanol sensitivity and acute functional tolerance in rats. Previous studies indicate common QTLs for NT receptor densities and NT levels in specific brain regions and ethanol-related behaviors in mice. Identification of common QTLs for NT measures and ethanol-related behaviors in rats would significantly strengthen the argument for pleiotropic effects of genes regulating these biochemical and behavioral phenotypes. These studies will utilize a genetically segregating F2 population derived from the HAS and LAS inbred strains; production of all animals will be performed in a separately funded project by Richard A. Deitrich. Studies are funded separately to perform the behavioral phenotyping and approximately 50 percent of the genotyping of the F2 rats. In those studies brains will be dissected and immediately frozen and stored for subsequent assay for NT-ir levels and receptors densities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROTOXICITY OF NMDA RECEPTOR ANTAGONISTS Principal Investigator & Institution: Sharp, Frank R.; Professor; Neurology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 31-JUL-2006 Summary: (Adapted from applicant?s abstract): The non-competitive NMDA receptor antagonists, including phencyclidine (PCP, angel dust), ketamine (Special K), and dizocilpine (MK-801), have been used as anesthetics, protect against experimental stroke, are increasing as drugs of abuse, and continue to be developed for treatment of various neurological diseases. However, these drugs produce psychosis in normal people and exacerbate psychosis in patients with schizophrenia. The drugs also injure rodent limbic cortex, killing some neurons and injuring others that have cytoplasmic vacuoles and express HSP7O and HO-i heat shock proteins. Since anti-psychotic drugs prevent the injury, the circuits mediating the injury in rodents may be similar to the circuits that mediate psychosis in humans. Our preliminary data demonstrate that NMDA antagonists injure limbic, retrosplenial cortex of rats by blocking NMDA receptors on GABA neurons in anterior thalamus, leading to thalamic excitotoxic injury of retrosplenial cortical pyramidal neurons via AMPA and other non-NMDA receptors. This proposal will continue to define the mechanisms of this neurotoxic injury. The first
36
Haloperidol
aim will determine whether injections of Dl, D2 and D4 dopamine receptor antagonists into retrosplenial cortex and anterior thalamus prevent the induction of HSP7O and other markers of injury produced by systemic PCP and MK-801. The second aim will determine whether blockade of NMDA receptors in substantia nigra (SN) and the adjacent ventral tegmental area (VTA) by PCP and ketamine produce and/or aggravate injury to retrosplenial cortex. The third aim will determine whether specific AMPA receptor antagonists, specific kainate receptor antagonists, and specific metabotropic glutamate receptor agents prevent injury to limbic cortex produced by systemic PCP and ketamine. The fourth aim will determine whether activation of substantia nigral ventral tegmental area and limbic cortex GABA receptors with GABA agonists prevent the injury produced by systemic PCP and MK-801. The fifth aim will determine whether visual sensory input contributes to the non-NMDA glutamate-mediated limbic cortical injury produced by NMDA antagonists. The last aim will determine whether NMDA receptor antagonists produce limbic cortical injury in cats and whether typical and atypical antipsychotic drugs, like haloperidol and clozapine, block injury. These studies will define the circuits and receptors that mediate the cortical injury produced by NMDA receptor antagonists in experimental animals. These studies will also contribute to understanding the circuits and transmitters that mediate psychosis due to psychomimetic drugs like PCP and Special K in people, and they will also contribute to understanding the circuits and receptors that mediate acute psychosis in patients with schizophrenia and other psychotic disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITION
NICOTINIC-ANTIPSYCHOTIC
DRUG
INTERACTIONS
AND
Principal Investigator & Institution: Levin, Edward D.; Associate Professor; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 12-DEC-2001; Project End 30-NOV-2006 Summary: Nicotine is self-administered via cigarette smoking by the great majority of patients with schizophrenia. Nicotine has direct effects on cognitive function and interacts with antipsychotic drugs to substantially influence their actions on cognitive function. The cognitive effects of nicotine may present a novel opportunity for improving the treatment of cognitive dysfunction associated with schizophrenia and cognitive dysfunction induced by antipsychotic drugs. Classical neuroleptics such as haloperidol and "atypical" antipsychotics such a clozapine and risperidone have substantially different mechanisms of action and likely interact with nicotine in quite different ways. The proposed project will determine the functional mechanisms by which nicotinic systems interact with antipsychotic drugs to affect cognitive function. Both classical and atypical antipsychotic drugs have been found to impair memory function. Haloperidol-induced working memory deficits have been found in our earlier studies of schizophrenic patients and laboratory rats to be reversed by acute doses of nicotine. Recently, we have found that the working memory impairment caused in rats by clozapine administration can be reversed by nicotine. These effects will be used as a forum in which to determine the critical neural mechanisms by which nicotine interacts with antipsychotic drugs in the control of memory function. We hypothesize that nicotinic receptor systems in the hippocampus are a key mechanism by which nicotine alleviates schizophrenia associated attentional impairment and antipsychotic druginduced memory impairment. Nicotinic innervation of the hippocampus has been found in our previous studies to be critical for nicotine effects on memory. Importantly, we have also shown that hippocampal DA innervation is also important for memory
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function. The proposed project will specify the mechanisms underlying nicotinic interactions with antipsychotic effects on memory function, including involvement of nicotinic receptor subtypes and their anatomic loci in hippocampus important for memory function. Dose response local infusion studies with selective nicotinic antagonist subtypes will be used to determine the relationship of nicotinic systems for memory performance in the benchmark radial-arm maze task as well as an operant attention task. These basic studies will help elucidate important therapeutic issues concerning the impact of nicotinic co- treatment with classic and atypical antipsychotic drugs to improve memory and attentional function. These studies will provide information concerning neural systems likely to underlie nicotinic actions we have seen on a systemic level and facilitate the development of new drug therapies for cognitive dysfunction in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OCCUPANCY OF EXTRASTRIATAL D2 RECEPTORS BY CLOZAPINE Principal Investigator & Institution: Kessler, Robert M.; Professor of Radiology; Radiology & Radiological Scis; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2003 Summary: (Verbatim from the Applicant's Abstract) The antipsychotic effects of typical neuroleptics are mediated by blockade of dopamine D2 type receptors. It has been proposed that the antipsychotic effects of these drugs are mediated by blockade of cortical and limbic dopamine D2 receptors while extrapyramidal site effects are mediated by dorsolateral striatal D2 receptor blockade. To date, most PET and SPECT studies of antipsychotic drug blockade of D2 receptors have examined the striatum. There are a number of studies which suggest that the atypical profile of clozapine is mediated at least in part by selective effects on cortical and limbic dopaminergic neurotransmission. Our group has developed [18F] N-allyl-5-fluoropropylepidepride as a PET radioligand for visualization of extrastriatal D2 receptors in man. Our Phase I and early Phase II IND studies demonstrate that this ligand allows excellent visualization and quantitation of extrastriatal D2 receptors in man. Wed propose to use [18F] N-allyl5-fluoropropylepidepride PET studies to evaluate 15 schizophrenic subjects off medication and following 6 weeks of haloperidol monotherapy, as well as 15 schizophrenic subjects off medication and following 8 weeks of clozapine monotherapy. The data from these studies will allow evaluation as to whether clozapine, s compared to haloperidol (a typical neuroleptic), selectively occupies extrastriatal dopamine D2 receptors, and whether regional occupancy of D2 receptors can be related to antipsychotic effects. Secondary goals include examining if psychopathological symptom complexes, i.e., positive, negative, and disorganization, as well as cognitive abnormalities in schizophrenia are related to regional levels of D2 receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OLANZAPINE DISEASE/DEMENTIA
FOR
PSYCHOSIS
IN
PARKINSON'S
Principal Investigator & Institution: Marsh, Laura; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Parkinson's disease (PD) affects 1% of the population over age 65. Psychotic symptoms occur in up to 40% of patients, and the majority of PD patients with psychosis
38
Haloperidol
also have dementia (up to 80%). Psychosis in PD is exceptionally challenging to manage since the development of psychotic symptoms will constrict the dose of antiparkinsonian medications, dose reductions or withdrawal of antiparkinsonian medications exacerbate motor symptoms, and antipsychotic medications can aggravate parkinsonism and worsen cognitive function. There is a crucial need for empirical data concerning safe and effective treatments of psychosis in PD. "Atypical" neuroleptic (antipsychotic) agents are potentially useful agents for treating psychosis in PD since their pharmacological profile renders them less likely to cause extrapyramidal symptoms than conventional antipsychotic medications, e.g., haloperidol or chlorpromazine. Olanzapine, released for treatment of psychosis in October, 1996, has potential applications in PD, but its dopamine blocking properties may increase the risk of adverse motor effects. This is clearly the case in some patients with PD, but it is unclear whether the presence or degree of dementia changes the tolerability to olanzapine. Accordingly, the overall aim of this investigation is to conduct a 6-week trial of olanzapine starting at 2.5 mg qhs to examine the efficacy, safety, and cognitive effects of olanzapine for treatment of psychosis in patients with PD and moderate to severe dementia The projected sample size is 15 subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OLANZAPINE VS HALOPERIDOL TREATMENT FOR ADOL ONSET SCHIZOPHRENIA Principal Investigator & Institution: Buchsbaum, Monte; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PALLIDAL GABA AND ATYPICALITY OF ANTIPSYCHOTIC DRUGS Principal Investigator & Institution: See, Ronald E.; Professor; Physiology and Neuroscience; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-DEC-1999; Project End 30-NOV-2003 Summary: Atypical anti-psychotic drugs (APDs) are primarily differentiated from typical APDs in that they possess a lower motor side effects profile. Experimental approaches to study "atypicality" have generally focused on cortical, striatal, and limbic dopamine terminal regions of the brain. However, research findings on motor syndromes and psychosis also support the critical role of striatopallidal gammaaminobutyric acid (GABA) pathways. Our specific global hypothesis is that decreases in pallidal GABA function mediate the atypical profile of certain APDs and may be a critical mechanism for the low incidence of motor side effects. Recent data from our laboratory has shown that typical APDs (e.g. haloperidol) produce motor side effects and increase GABA release in the globus pallidus, while atypical APDs (e.g. clozapine) produce minimal motor side effects and decrease GABA release in the globus pallidus. Furthermore, only clozapine has an effect on decreasing GABA in the ventral pallidum, a pallidal subregion believed to preferentially mediate "limbic" striatal output. The effect of atypical APDs may result form an inhibition of presynaptic release of GABA, since the density of nerve terminal GABA immunolabeling is increased after clozapine injection. This paradigm of altered GABA release in pallidal pathways could provide clues regarding the low incidence of motor side effects with atypical APDs and further
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39
our understanding of pallidal GABA in mediating atypical APD action. The series of studies proposed here will utilize a rodent model of acute and chronic APD administration to answer several questions. The first set of experiments will examine changes in extracellular and presynaptic pallidal GABA after systematic and sitespecific administration of drugs with a high or low motor side effect profile. In order to test the possibility that 5-HT2 receptor subtypes play a role in mediating pallidal GABA function, a second series of experiments will assess 5-HT2A and 5-HT2C receptor agonism and antagonism on pallidal GABA function. In a final set of studies, pallidal GABA function and motor activity will be studied after prolonged periods of APD administration which are similar to the treatment durations utilized in psychotic patients. These studies will provide new insights on the mechanisms of action of APDs and provide a novel means of identifying putative atypical APDs. The information obtained will facilitate the development of optimal pharmacotherapy for mental disorders, particularly schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARTIAL SCHIZOPHRENIA
DOPAMINEAGONIST
TREATMENT
OF
Principal Investigator & Institution: Tamminga, Carol A.; Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-SEP-1992; Project End 31-MAR-2003 Summary: The strategy of using partial dopamine (DA) agonists as antidopaminergic antipsychotic agents is based on two sets of observations: first, that DA neurons have autoreceptors which function to decrease DA synthesis, release and neuronal firing, and hence mediate antidopaminergic signals; and, second, that partial agonists have full affinity but reduced intrinsic activity at DA receptors, consequently they exert relatively lower receptor stimulation in competition with the natural neurotransmitter, dopamine. The investigators have suggested that antipsychotic treatment with partial DA agonists, compared to treatment with DA receptor antagonists may have significant clinical advantages. Efficacy and side effects of partial DA agonists will depend on the level intrinsic activity of the partial agonist, a range which can extend from less than 10 percent to over 90 percent. The investigators work to date (see Progress Report) suggests that a partial agonist activity somewhat below 40 percent may be optimal for schizophrenia. The investigators most useful partial DA agonist is (-)-3PPP. The strategy of combining a small proporb'on of a full antagonist (e.g. haloperidol or clozopine) with the partial agonist (-)-3PPP, to produce a functionally lower intrinsic activity of (-)-3PPP, adds flexibility to the clinical testing of the partial agonist strategy. The investigators first clinical study will focus on testing the antipsychotic action of a very low dose of haloperidol (0.5 haloperidol + (-)-3PPP (flexible dose range) or (-)3PPP placebo, compared to a third active control arm (5 mg bid haloperidol + (-)-3PPP placebo). Treatment in each of these three aims will be evaluated in the three primary symptom cluster of schizophrenia: 1) hallucinations/delusions; 2) disorganization, and 3) negative symptoms, and on cognitive function. Our second study will be designed exactly like the first study, except that a very low dose of clazopine will be utilized. Clazapine is low affinity tigand and may, in combination with (-)-3PPP, produce a better antipsychotic action based on its greater displacability. Because the investigators have already demonstrated significant efflcacy, but efflcacy to which tolerance occurs, the investigators current goal is to demonstrate that the efficacy of (-)-3PPP treatment, by modifying intrinsic activity and dosing schedules can be extended. If the investigators are able to overcome the efficacy tolerance, then one of these treatments would be ready
40
Haloperidol
for broader multicenter testing. Application of this strategy to other syndromes where neuroleptics improve psychosis is also indicated. In the biochemistry laboratory, we propose to use the D2', D4 2. D4 4 and D4 7 cloned receptors in cultured CHO cells to examine the intrinsic activity and the desensitization potential of different DA agonists at the human D2-family receptors, in vitro. Cloned receptor desensitization, change in GTPyS activation, and arachidonic acid release will be used to study the mechanisms of tolerance and desensitization operating here. These data will predict and later help us to select optimal agonist intrinsic activity ior clinical testing for antipsychotic actvity, duration of therapeutic action, and side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOPHYSIOLOGY PARKINSONISM
OF
THE
BASAL
GANGLIA
IN
Principal Investigator & Institution: Wichman, Thomas; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002 Summary: The most widely held model of the pathophysiology of Parkinson's disease postulates that striatal dopamine loss in parkinsonism results increased striatal inhibition of the external pallidal segment (GPe), which leads to disinhibition of the subthalamic nucleus (STN) and internal pallidal segment (GPi). Increased STN and GPi activity is known to be crucial for parkinsonian signs. This model has greatly facilitated the development of new treatment approaches to parkinsonian, but has recently been criticized on the basis of new anatomical and biochemical data. In particular, the role of altered activity in GPe in parkinsonism has been challenged, and, related to this, the view that STN activity is increased in parkinsonism due to release from inhibition via GPe efferents has come under attack. Alternative mechanisms that were proposed to explain increased STN activity include increased glutamateric excitation of STN via efferents from cortex, thalamus or midbrain and reduced inhibition via mesencephalic dopaminergic inputs. The proposed experiments address these issues in normal and parkinsonian Rhesus monkeys. Microdialysis measurements of changes in transmitter levels will be used to assess changes in activity along GPe efferents, will be correlated with changes in discharge characteristics of neurons in GPe, and with changes in the activity of the GABA synthesizing enzyme, GAD/67, in the STN (S.A.1.). Behavioral consequences of GPe inactivation will be explored with injections of the GABA receptor agonist muscimol into GPe (S.A.2). The cause(s) for increased discharge along the STNGPi pathway will be assessed with experiments measuring changes in glutamate levels in GPi in response to pharmacologic manipulation of dopaminergic, GABAergic and glutamatergic transmission in the STN (S.A.3). Finally, the hypothesis that parkinsonism-induced changes in the activity of basal ganglia pathways can be explained by striatal dopamine depletion will be tested with biochemical and behavioral experiments in which dopaminergic transmission in the striatum is transiently interrupted by intrastriatal injections of the dopamine antagonist haloperidol in normal animals, or restored by similar injections of the dopamine receptor agonist quinpirole in parkinsonian monkeys (S.A. 4). These experiments will better define the functional importance of changes in activity along the pathways connecting the basal ganglial nuclei in Parkinson's disease. This information is essential for the future development of rational pharmacological and neurosurgical treatments of parkinsonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PET IMAGING OF CENTRAL SEROTONIN RECEPTORS & REUPTAKE SITES Principal Investigator & Institution: Wong, Dean F.; Vice Chair for Research; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: This study is based on three hypotheses: 1) 5-HT2A serotonin density is decreased in the cortex of schizophrenia patients, 2) 5HT reuptake sites are decreased in SCZ, and 3) the ratio of the 5HT2A/5HT reuptake sites may be abnormal. [11C]MDL100,907, a radiolabeled form of atypical antipsychotic, and [11C]McN5652 that binds with the affinity and selectivity to the 5HT2A receptor and 5HT transporter, respectively, will provide superior information about density of 5-HT2 receptors in the living human brain relative to other ligands that have less receptor specificity. MDL100,907 is a new and highly selective 5HT2A ligand under development in clinical trials of schizophrenia. McN5652(+)is potent reuptake inhibitor and its McN5652 can be used for non-specific binding measure. Studies will be carried out on patients meeting DSMIV criteria for chronic schizophrenia. They will either be drug free or receiving one of two typical antipsychotics, Haldol or Prolixin. These two drugs have low but different affinity to 5HT2A receptor. Studies are performed on an age and gender matched control group. All subjects are on a tryptophan free diet for 24 hours prior to the study. All drug free patients will be studied under Hypothesis 1, 2 and 3. All patients who are currently on medications are studied under hypothesis 2 and 3. All controls are studied under hypothesis 1, 2 and 3. We will evaluate the reliability of the measurements of 5HT2 receptor and transporter in schizophrenics receiving typical antipsychotics. This was done by studying 2-5 normal subjects before and after taking one dose of the same antipsychotic, 7.5 mg of Haldol or 4mg of Prolixin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOLOGICAL BASIS OF DECISION-MAKING Principal Investigator & Institution: Bechara, Antoine; Assistant Professor; Neurology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: (adapted from applicants abstract): The long term goal of this project is elucidation of the pharmacological basis of decision making, a term which is often referred to in the psychological literature as "executive functions," and the application of the derived knowledge to the treatment and prevention of substance abuse. Both substance abusers and patients with ventromedial prefrontal frontal lobe lesions suffer from impairments in decision-making. Here we plan to study frontal patients and extend the findings to substance abusers. The proposal is guided by a theoretical framework designed to account for the defects in reasoning and decision-making that are so salient in frontal patients. The hypothesis posits that those decision-making defects, specifically those which involve personal and social behavior, are the results of defective activation of somatic markers that normally function as covert or overt signposts for helping with the process of making choices which are advantageous to the organism. In the past few years, we investigated the anatomical, physiological, and cognitive aspects of the neural network presumed to underlie decision-making and somatic marker activation. We found that the failure to enact somatic states results from dysfunction in a neural system in which the ventromedial (VM) prefrontal cortex is one critical region. However, other neural regions, including the amygdala and somatosensory cortices (SI, SII, and insula) are also hypothesized to be components of
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that same neural system. The operation of this system is thought to be influenced by non-specific neurotransmitter systems through direct or indirect anatomical connections. However, the nature of these neurotransmitter systems, has not been elucidated. Using experimental strategies which we perfected in the study of these patients, here we propose to carry out specific neurotransmitter manipulations and investigate their effects on decision-making in normals and in patients with frontal lobe lesions. In addition, we plan to investigate how another frontal lobe function, namely working memory, is affected by the same manipulations, relative to decision-making. Recent evidence has established that substance abusers suffer from decision-making impairments as revealed by the same laboratory tests which we used to study frontal patients. Ongoing investigations are probing further the link between decision-making, the frontal lobe, and substance abuse. Therefore, the results from this project will help the development of pharmacological therapies that assist in the rehabilitation of 1) substance abusers; and 2) many patients who suffer from disturbances of executive function caused by head injury, stroke, and surgical ablation of tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDICTION
PHARMACOLOGICAL
SUBSTRATES
OF
AMPHETAMINE
Principal Investigator & Institution: Brauer, Lisa H.; Assistant Research Professor; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREFRONTAL CELL PATHOLOGY DISTINGUISHES MENTAL DISORDERS Principal Investigator & Institution: Rajkowska, Grazyna; Professor of Psychiatry; Psychiatry and Human Behavior; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 23-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) There are established differences and similarities in phenomenology and treatment between schizophrenia (SCHZ) and major depressive disorder (MDD). It is well known that depressed symptoms occur in SCHZ and psychotic symptoms are no uncommon for MDD. It is therefore justified to postulate that different brain regions and/or different cell types using specith neurotransmitters are crucial to distinguish the neuropathology of both disorders. Neuroimaging evidence implicates the dorsolateral prefrontal (dIPFC) and orbitofrontal (ORB) cortical areas in the neuropathology of SCHZ and MDD. Our recent quantitative histopathological studies in postmortem tissue reveal the differential involvement of the dIPFC and ORB region in the neurobiology of MDD and SCHZ. However, the specific types of neurons and glia, which underlie the prefrontal pathology of these mental disorders have not been identified yet. The overall objective of this proposal is to distinguish MDD and SCFIZ by using quantitative immunohistochemistry to identify the region-and layerspecific biochemical types o vulnerableneurons and glia constituting dysfunctional prefrontal Circuits. The specific hypotheses are: 1) Subjects with MDD will be characterized by lower numbers of immunoreactive neurons and glia and lower levels of trophic factors, BDNF an GDNF in both dIPFC and ORB. In contrast, subjects with SCHZ will exhibit reductions similar to MDD only in the ORI region, whereas in the
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dIPFC, SCHZ will be distinguished from MDD by higher neuronal and possibly, glial cell number. 2 Cellular changes observed in prefrontal regions from MDD and SCHZ patients are due to the disease process and therefore they will not be found in analogous regions from rat brains treated chronically with antidepressant or antipsychotic medications If these hypotheses are proven, a provocative interpretation would be that anatomic-functional changes in the dIPFC may b related to cognitive dysfunction. Where as changes in the ORB may be related to depressive symptoms. To test these hypotheses vulnerable cell types will be identified and quantified by the combination of immunohistochemistry and 3-D non-biase stereology. We will identify prefrontal cells with specific antibodies (Nonpyramidal neurons with antibodies to Ca2 binding proteins; Pyramidal neurons with antibodies against neurofilament protein NF-200; Astroglia with an antibody to GFAP; ani-Microglia with antibodies against the bchemokine receptor in subjects with MDD, subjects with SCHZ and in match psychiatrically-normal controls. The proposed study will illuminate disrupted cortical circuits involved in psychotic and depressed symptomatology and possibly cortical Sites of action for antidepressant and antipsychotic medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRO-LEU-GLY-NH2 AND DOPAMINE RECEPTOR MODULATION Principal Investigator & Institution: Johnson, Rodney L.; Professor; Medicinal Chemistry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-DEC-1983; Project End 31-MAY-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION /ANTIDEPRESSANT
OF
ADULT
NEUROGENESIS--STRESS
Principal Investigator & Institution: Duman, Ronald S.; Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 16-JUL-2002; Project End 30-JUN-2006 Summary: Recent clinical studies demonstrate that depression, as well as other psychiatric illnesses can result in a reduce in the volume and function of the hippocampus Pre-clinical studies in rodents in rodents and non- human primates demonstrate that stress can result in morphological alterations of hippocampal neurons, including atrophy and reduced cell proliferation. Stress is also reported to decrease the expression of brain derived neurotrophic factor Although hippocampus is only one of several brain regions implicated in depression, the structural alterations of hippocampus could be related to certain cognitive and vegetative abnormalities in depressed patients. These findings also raise the possibility that the therapeutic action of anti-depressants could occur, in part, via reversal or blockade of these alterations. This hypothesis is supported by our recent studies demonstrated that anti- depressant treatment increases neurogenesis in adult rodent hippocampus. This effect is dependent on chronic administration and is observed with different classes of antidepressants , suggesting that increased neurogenesis is a common action of this type of medication. Preliminary studies also demonstrate that anti-depressant administration blocks the down-regulation of neurogenesis that is caused by stress. The focus of the current application is to determine the molecular mechanisms that mediate the effect of antidepressants on adult neurogenesis Our previous studies, supported by this grant,
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Haloperidol
demonstrated that anti-depressants up-regulate the cAMP response element binding protein (CREB), a transcription factor implicated in cellular plasticity, and brain derived neurotrophic factor. We will use a combination of pharmacological and mutant mouse models to study the role of CREB and BDNF in adult neurogenesis and in the response to antidepressant treatment. Preliminary studies demonstrate that administration of a drug which blocks cAMP metabolism (rolipram) increases, while over- expression of a dominant negative mutant of CREB decreases, neurogenesis in adult hippocampus. We will also examine additional gene targets of CREB that could influence the differentiation and survival of newborn cells in the adult hippocampus. Finally, studies will be conducted to examine the relationship between adult neurogenesis and behavior responses to anti-depressant treatment. These studies will provide new insight on the molecular mechanisms that control neurogenesis in adult hippocampus and of the role of these pathways in the action of anti-depressant treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SOMATODENTRITIC DOPAMINE RELEASE Principal Investigator & Institution: Cobb, William S.; None; Rutgers the State Univ of Nj Newark Blumenthal Hall, Suite 206 Newark, Nj 07102 Timing: Fiscal Year 2002; Project Start 01-JUN-2002 Summary: In addition to releasing dopamine from nerve terminals in striatum, nigrostriatal dopamine neurons are also capable of releasing dopamine from somatodendritic regions in substantia nigra. These two processes share fundamental similarities including calcium-dependence, voltage- sensitivity and storage in vesicles. While the biological mechanisms of release in both regions are similar, it is unknown to what extent somatodendritic and nerve terminal release are coupled to one another. While nerve terminal release and impulse activity are highly correlated, it is unknown to what magnitude nerve impulse activity generated in the initial segment affects dopamine release in the dendrites. In addition, much is known about the effects of neurochemical and neuroanatomical afferents on dopamine release from axon terminals, however, this has never been examined systematically for somatodendritic release in substantia nigra. In order to investigate this further, in vivo microdialysis coupled to electrochemical detection will be used to measure the effects of manipulation of glutamate and GAGA neurotransmission within substantia nigra as well as alterations in the afferent input from subthalamic nucleus and globus pallidus to substantia nigra under normal conditions and after systemic haloperidol administration on somatodendritic dopamine efflux. In the final set of experiments, extracellular recording of dopamine neurons combined with measurement of nigral dopamine efflux by microdialysis will be performed in order to study the relationship between nerve impulse activity and somatodendritic dopamine release. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SCHIZOPHRENIA: PROGRESSION
MOLECULAR
MARKERS
OF
DISEASE
Principal Investigator & Institution: Thomas, Elizabeth A.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAY-2009 Summary: (provided by applicant): Schizophrenia is a life-long mental illness with variable expression and unknown etiology. The major clinical manifestations of schizophrenia at disease onset are psychotic symptoms; however, as the illness
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progresses the negative symptoms become more predominant. In addition, many other neurological aspects change over the course of illness. The molecular factors that influence symptom presentation and the course of schizophrenia after its onset and how treatment modifies the effects of illness remain important and essentially unaddressed questions. Our goals in this application are to identify genes that have altered levels of expression in the CNS of individual subjects who have had a short or long duration of illness using the automate method Total Gene expression Analysis (TOGA*/R). We will generate gene expression profiles from the prefrontal and temporal cortices of individual schizophrenic subjects at different stages of illness: 10 acute schizophrenic subjects (illness duration 22 yrs) and 20 controls, age- and sex- matched to both disease cohorts (n=80 expression profiles total). Since correct treatment early in the illness is thought to have a beneficial affect on the outcome of the disease, the identification of genes involved in the early versus late stages of disease will be important for understanding disease progression. We will also investigate disease heterogeneity in the schizophrenia syndrome by distinguishing gene expression patterns that are present in subsets of all schizophrenic individuals. We will further characterize how the expression of antipsychotic drug-regulated genes (previously identified in mice) is altered in human subjects with schizophrenia in order to elucidate potential consequences of antipsychotic drug exposure in humans. This will be accomplished by measuring expression differences of candidate genes in postmortem brain samples from chronic schizophrenic subjects by real-time PCR, in situ hybridization and Western blot analyses. Overall, these studies may lead to approaches that will favorably alter the course, treatment and outcome of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SIGMA RECEPTOR STRUCTURE /FUNCTION/K+ CHANNEL MODULATION Principal Investigator & Institution: Ruoho, Arnold E.; Professor and Chair; Pharmacology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Sigma receptors are unique "non-opioid" receptors that are found in the mammalian central nervous system and peripheral organs. The function of the sigma receptor is unknown, but it is believed to mediate the immunosuppressant, antipsychotic, and neuroprotective effects of drugs, such as haloperidol, ditolylguanidine (DTG), pentazocine, and cocaine. Several observations indicate potential therapeutic uses of sigma ligands. Some atypical neuroleptics (e.g., haloperidol) have high affinity for the sigma receptor, which has led to the possibility of creating a new class of antipsychotic drugs, which are devoid of dopaminergic activity and can bind selectively to the sigma receptor. A genetic linkage has been reported for the sigma receptor and schizophrenia. Selective sigma ligands can block the behavioral and toxic functions of cocaine, and cocaine can also serve as a sigma ligand with reasonable affinity. These observations raise the possibility that the sigma receptor may be a target for the treatment of cocaine-related responses. The potent immunosuppressant SR31747A, which binds to the sigma receptor, exhibits immunosuppressive properties and antiproliferative activity in mouse and human T lymphocytes. These observations may explain the immunosuppressant properties of cocaine and other sigma ligands and lead to a new generation of immunosuppressants. A number of studies have shown that sigma receptor ligands modulate ion channels in the plasma membrane to regulate excitability. Target channels are general voltage-gated K+ channels, and the modulation entails an inhibition of the current elicited by positive
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Haloperidol
voltage steps. The focus of this research proposal is to characterize the structure of the sigma1 receptor binding site and the manner by which the sigma1 receptor modulates K+ channels. Three areas of focus will be investigated: (1) synthesis and characterization of novel high affinity sigma receptor agonist and antagonist photo affinity labels; (2) mapping the ligand binding site(s) of the sigma1 receptor; and (3) determination of the properties of the sigma1 receptor interaction with Kvl.4 potassium channels and other protein partners. These experiments will be performed through the combined use of photoactivatable molecules, electrophysiology, and recombinant and fusion proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STARTLE TREATMENTS
REFLEX--TESTING
ALCOHOL
PATIENTS
AND
Principal Investigator & Institution: Hutchison, Kent E.; Professor; Psychology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 21-SEP-1998; Project End 31-AUG-2004 Summary: The neural circuitry that mediates prepulse inhibition of the startle reflex (PPI) overlaps considerably with the neural mechanisms (e.g., mesolimbic structures and dopamine activity) that mediate alcohol- induced and alcohol cue-induced changes in mesolimbic dopamine activity. Given this congruence in neural circuitry, PPI has considerable promise as a centrally mediated and biologically based measure of the mesolimbic activating effects of alcohol and alcohol cues. The long-term objective of this research is to develop PPI as an integral component of a paradigm that will be used to test current assumptions about the biological (e.g., dopamine activity) and cognitive processes (e.g., subjective stimulation, reinforcement, and craving) that underlie the acquisition and expression of addictive behavior. Specifically, this research will test the following primary hypotheses: 1) Intravenous administration of a low dose of alcohol in moderate to heavy social drinkers decrease prepulse inhibition of the startle response and increases self-reported stimulation; 2) These effects are mediated in part by mesolimbic dopamine activity and therefore should be blocked by a drug that is known to reduce dopamine activity in these structures (e.g., haloperidol); 3) Exposure to alcohol cues in alcohol dependent patients results in decreases prepulse inhibition of the startle response and increases urge to drink; 4) These effects are also mediated in part by mesolimbic dopamine and can be blocked with a drug that reduces dopamine activity (e.g., haloperidol). Hypotheses 1 and 2 will be tested in a 2 x 2 factorial design, in which intravenous infusion of alcohol will be compared with saline infusion and crossed with haloperidol and placebo using the startle reflex and self-report measures of stimulation and affect as dependent variables. Hypotheses 3 and 4 test will be tested in a 2 x 2 factorial design, in which control cues will be compared with alcohol cues and crossed with haloperidol and placebo. The findings of these studies are expected to lead to a more detailed conceptualization of the biological and cognitive underpinnings of alcohol dependence and guide the development of new interventions for alcohol dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUSTAINED RELEASE OLANZAPINE Principal Investigator & Institution: Smith, Thomas J.; Auritec Pharmaceuticals, Llc 738 Main St, Ste 409 Waltham, Ma 02451 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2005
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Summary: (provided by applicant): The long-term goal of this research is to minimize morbidity associated with psychotic disorders by developing injectable long-acting formulations of olanzapine (Zyprexa/R), currently a leading atypical antipsychotic agent FDA approved for the treatment of schizophrenia and mania. Because the drug has a moderate elimination half-life, once daily therapy is usually sufficient. However, adherence to daily oral therapy is a major problem in populations required to take the drug as outpatients for prolonged maintenance therapy, substantially limiting its longterm effectiveness. Long-term adherence to antipsychotic treatment can be enhanced with long-acting, injectable preparations (currently only long-chain fatty acid esters of fluphenazine or haloperidol are licensed in the US), but no long-acting preparation has yet been licensed for a modern antipsychotic drug with an atypically low risk of adverse extrapyramidal neurological effects (EPS) strongly associated with older neuroleptic agents. Auritec Pharmaceuticals is developing a novel technology that yields nonderivitized formulations of olanzapine and other agents for injection. Such a long acting, sustained-release preparation of olanzapine is being developed to provide adequately sustained dosing for monthly administration. Such a preparation of olanzapine promises significant innovation for the in the treatment of schizophrenia, mania, and other highly prevalent, incurable, psychotic disorders. Specific aims of this Phase I proposal are to: 1. Formulate a sustained release suspension for olanzapine based on our proprietary MacrocrystalTM technology. 2. Test the in vitro release-by-time characteristics of this formulation into buffer. 3. Test the in vivo pharmacokinetics and provide a preliminary assessment of the duration of the formulation in rats. 4. Test the pharmacodynamics of the formulation in a rat model. Completion of these aims will constitute a readily identifiable milestone that will continue in Phase 2, in which we will more definitively clarify the potency, duration of action, and safety of the formulation in animal models and complete other laboratory studies required for an investigational New Drug Exemption from the FDA for initial clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
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Haloperidol
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 “haloperidol” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for haloperidol in the PubMed Central database: •
Actigraphic measurement of the effects of single-dose haloperidol and olanzapine on spontaneous motor activity in normal subjects. by Kiang M, Daskalakis ZJ, Christensen BK, Remington G, Kapur S.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165794
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Increase of proenkephalin mRNA and enkephalin content of rat striatum after daily injection of haloperidol for 2 to 3 weeks. by Tang F, Costa E, Schwartz JP.; 1983 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=394148
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Loss of haloperidol induced gene expression and catalepsy in protein kinase Adeficient mice. by Adams MR, Brandon EP, Chartoff EH, Idzerda RL, Dorsa DM, McKnight GS.; 1997 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23735
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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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Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. by [No authors listed]; 2003 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=200800
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Ritanserin as an adjunct to lithium and haloperidol for the treatment of medicationnaive patients with acute mania: a double blind and placebo controlled trial. by Akhondzadeh S, Mohajari H, Mohammadi MR, Amini H.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194858
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Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study). by Garcia-Cabeza I, Gomez JC, Sacristan JA, Edgell E, Gonzalez de Chavez M.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65550
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 haloperidol, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “haloperidol” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for haloperidol (hyperlinks lead to article summaries): •
A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania. Author(s): Tohen M, Goldberg JF, Gonzalez-Pinto Arrillaga AM, Azorin JM, Vieta E, Hardy-Bayle MC, Lawson WB, Emsley RA, Zhang F, Baker RW, Risser RC, Namjoshi MA, Evans AR, Breier A. Source: Archives of General Psychiatry. 2003 December; 60(12): 1218-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662554
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A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. Author(s): Hirsch SR, Kissling W, Bauml J, Power A, O'Connor R. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 516-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088164
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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 case of child abuse: haloperidol poisoning of a child caused by his mother. Author(s): Satar S, Yilmaz HL, Gokel Y, Toprak N. Source: European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. 2001 December; 8(4): 317-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11785601
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A comparison of the efficacy and safety of olanzapine versus haloperidol during transition from intramuscular to oral therapy. Author(s): Wright P, Meehan K, Birkett M, Lindborg SR, Taylor CC, Morris P, Breier A. Source: Clinical Therapeutics. 2003 May; 25(5): 1420-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867218
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A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Author(s): Breier A, Meehan K, Birkett M, David S, Ferchland I, Sutton V, Taylor CC, Palmer R, Dossenbach M, Kiesler G, Brook S, Wright P. Source: Archives of General Psychiatry. 2002 May; 59(5): 441-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11982448
•
A multidose study of haloperidol decanoate in the maintenance treatment of schizophrenia. Author(s): Kane JM, Davis JM, Schooler N, Marder S, Casey D, Brauzer B, Mintz J, Conley R. Source: The American Journal of Psychiatry. 2002 April; 159(4): 554-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11925292
•
A pilot cross-over design study on QTc interval prolongation associated with sulpiride and haloperidol. Author(s): Su KP, Shen WW, Chuang CL, Chen KP, Chen CC. Source: Schizophrenia Research. 2003 January 1; 59(1): 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413648
•
A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial. Author(s): Sikich L, Hamer RM, Bashford RA, Sheitman BB, Lieberman JA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 January; 29(1): 133-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583740
Studies
51
•
A post hoc analysis of the impact on hostility and agitation of quetiapine and haloperidol among patients with schizophrenia. Author(s): Chengappa KN, Goldstein JM, Greenwood M, John V, Levine J. Source: Clinical Therapeutics. 2003 February; 25(2): 530-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749512
•
A single-blind, randomized trial comparing quetiapine and haloperidol in the treatment of tardive dyskinesia. Author(s): Emsley R, Turner HJ, Schronen J, Botha K, Smit R, Oosthuizen PP. Source: The Journal of Clinical Psychiatry. 2004 May; 65(5): 696-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15163258
•
Actigraphic measurement of the effects of single-dose haloperidol and olanzapine on spontaneous motor activity in normal subjects. Author(s): Kiang M, Daskalakis ZJ, Christensen BK, Remington G, Kapur S. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 July; 28(4): 293-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921224
•
Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. Author(s): Currier GW, Chou JC, Feifel D, Bossie CA, Turkoz I, Mahmoud RA, Gharabawi GM. Source: The Journal of Clinical Psychiatry. 2004 March; 65(3): 386-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096079
•
Adverse effects of risperidone and haloperidol treatment in schizophrenia. Author(s): Yen YC, Lung FW, Chong MY. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2004 March; 28(2): 285-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751424
•
Age-related alteration of haloperidol-serum protein binding. Author(s): Koyama H, Mori S, Sugioka N, Nishihara T, Nakajima K. Source: The Journal of Pharmacy and Pharmacology. 2003 January; 55(1): 77-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12625870
•
Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone. Author(s): Peuskens J, Moller HJ, Puech A. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 August; 12(4): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126869
52
Haloperidol
•
An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics. Author(s): Tilden D, Aristides M, Meddis D, Burns T. Source: Clinical Therapeutics. 2002 October; 24(10): 1648-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462294
•
An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine. Author(s): Carlson CD, Cavazzoni PA, Berg PH, Wei H, Beasley CM, Kane JM. Source: The Journal of Clinical Psychiatry. 2003 August; 64(8): 898-906. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927004
•
An online misadventure with haloperidol. Author(s): Barnes Recker CK, Hoehns JD, Sutherland JE, Opheim EF. Source: The Annals of Pharmacotherapy. 2003 October; 37(10): 1531. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519026
•
Assessment of the contributions of CYP3A4 and CYP3A5 in the metabolism of the antipsychotic agent haloperidol to its potentially neurotoxic pyridinium metabolite and effect of antidepressants on the bioactivation pathway. Author(s): Kalgutkar AS, Taylor TJ, Venkatakrishnan K, Isin EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 March; 31(3): 243-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584149
•
Atypical neuroleptic malignant syndrome with clozapine and subsequent haloperidol treatment. Author(s): Spivak M, Adams B, Crockford D. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 February; 48(1): 66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635570
•
Basal and haloperidol-stimulated prolactin and symptoms of nonaffective and affective psychoses in neuroleptic-free men. Author(s): Keks NA, Copolov DL, McKenzie DP, Kulkarni J, Hill C, Hope JD, Singh BS. Source: Biological Psychiatry. 1995 February 15; 37(4): 229-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7711159
Studies
53
•
Basal and haloperidol-stimulated prolactin in neuroleptic-free men with schizophrenia defined by 11 diagnostic systems. Author(s): Keks NA, Copolov DL, Kulkarni J, Mackie B, Singh BS, McGorry P, Rubin RT, Hassett A, McLaughlin M, van Riel R. Source: Biological Psychiatry. 1990 June 1; 27(11): 1203-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2354227
•
Behavioral effects of haloperidol in young autistic children. An objective analysis using a within-subjects reversal design. Author(s): Cohen IL, Campbell M, Posner D, Small AM, Triebel D, Anderson LT. Source: J Am Acad Child Psychiatry. 1980 Autumn; 19(4): 665-77. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7204797
•
Behavioral efficacy of haloperidol and lithium carbonate. A comparison in hospitalized aggressive children with conduct disorder. Author(s): Campbell M, Small AM, Green WH, Jennings SJ, Perry R, Bennett WG, Anderson L. Source: Archives of General Psychiatry. 1984 July; 41(7): 650-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6428371
•
Behavioral supersensitivity to beta-phenylethylamine after chronic administration of haloperidol. Author(s): Stoff DM, Jeste DV, Gillin JC, Moja EA, Cohen L, Stauderman KA, Wyatt RJ. Source: Biological Psychiatry. 1984 January; 19(1): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6538440
•
Behavioral vs biochemical prediction of clinical stability following haloperidol withdrawal in schizophrenia. Author(s): van Kammen DP, Kelley ME, Gurklis JA, Gilbertson MW, Yao JK, Peters JL. Source: Archives of General Psychiatry. 1995 August; 52(8): 673-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7543265
•
Beneficial effect of the addition of the 5-HT 2A/2C and alpha2 antagonist mianserin to ongoing haloperidol treatment in drug-resistant chronically hospitalized schizophrenic patients. Author(s): Grinshpoon A, Valevski A, Moskowitz M, Weizman A. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2000 September; 15(6): 388-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11004734
54
Haloperidol
•
Binding of the neuroleptic drug haloperidol to a monoclonal antibody: refinement of the binding site molecular model using canonical structures. Author(s): Anchin JM, Subramaniam S, Linthicum DS. Source: Journal of Molecular Recognition : Jmr. 1991 February; 4(1): 7-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1931126
•
Biperiden and haloperidol plasma levels and extrapyramidal side effects in schizophrenic patients. Author(s): Meszaros K, Lenzinger E, Hornik K, Schonbeck G, Hatzinger R, Langer G, Sieghart W, Aschauer HN. Source: Neuropsychobiology. 1997; 36(2): 69-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9267855
•
Biphasic effects of direct, but not indirect, GABA mimetics and antagonists on haloperidol-induced catalepsy. Author(s): Worms P, Lloyd KG. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1980 March; 311(2): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7189827
•
Blind, controlled, long-term study of the comparative incidence of treatmentemergent tardive dyskinesia with olanzapine or haloperidol. Author(s): Tollefson GD, Beasley CM Jr, Tamura RN, Tran PV, Potvin JH. Source: The American Journal of Psychiatry. 1997 September; 154(9): 1248-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9286184
•
Blink rate response to haloperidol as possible predictor of therapeutic outcome. Author(s): Bartko G, Herczeg I, Zador G. Source: Biological Psychiatry. 1990 January 1; 27(1): 113-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2297547
•
Blood choline and response to clonazepam and haloperidol in Tourette's syndrome. Author(s): Merikangas JR, Merikangas KR, Kopp U, Hanin I. Source: Acta Psychiatrica Scandinavica. 1985 October; 72(4): 395-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3865498
•
Blood levels of haloperidol and clinical outcome in schizophrenia. Author(s): Doddi S, Rifkin A, Karajgi B, Cooper T, Borenstein M. Source: Journal of Clinical Psychopharmacology. 1994 June; 14(3): 187-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027415
Studies
55
•
Blood levels of haloperidol and thioridazine during maintenance neuroleptic treatment of schizophrenic outpatients. Author(s): Shvartsburd A, Sajadi C, Morton V, Mirabi M, Gordon J, Smith RC. Source: Journal of Clinical Psychopharmacology. 1984 August; 4(4): 194-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6470190
•
Blood levels of reduced haloperidol versus clinical efficacy and extrapyramidal side effects of haloperidol. Author(s): Lane HY, Lin HN, Hu OY, Chen CC, Jann MW, Chang WH. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1997 February; 21(2): 299-311. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9061775
•
Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms. Author(s): Wolkin A, Sanfilipo M, Duncan E, Angrist B, Wolf AP, Cooper TB, Brodie JD, Laska E, Rotrosen JP. Source: The American Journal of Psychiatry. 1996 March; 153(3): 346-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8610821
•
Brachial plexus palsy with the use of haloperidol and a geriatric chair. Author(s): King T, Mallet L. Source: Dicp. 1991 October; 25(10): 1072-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1803793
•
Brain mechanisms of visual encoding and working memory in psychometrically identified schizotypal individuals and after acute administration of haloperidol. Author(s): Kopp B, Wolff M, Hruska C, Reischies FM. Source: Psychophysiology. 2002 July; 39(4): 459-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12212638
•
Brief report: haloperidol treatment of trichotillomania in a boy with autism and mental retardation. Author(s): Ghaziuddin M, Tsai LY, Ghaziuddin N. Source: Journal of Autism and Developmental Disorders. 1991 September; 21(3): 365-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1938782
•
Cardiovascular effects of 0.5 milligrams per kilogram oral d-amphetamine and possible attenuation by haloperidol. Author(s): Angrist B, Sanfilipo M, Wolkin A. Source: Clinical Neuropharmacology. 2001 May-June; 24(3): 139-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391124
56
Haloperidol
•
Cerebellar ataxia with intravenous valproate and haloperidol. Author(s): Ranjan S, Jagadheesan K, Nizamie SH. Source: The Australian and New Zealand Journal of Psychiatry. 2002 April; 36(2): 268. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11982555
•
Clomipramine versus haloperidol in the treatment of autistic disorder: a doubleblind, placebo-controlled, crossover study. Author(s): Remington G, Sloman L, Konstantareas M, Parker K, Gow R. Source: Journal of Clinical Psychopharmacology. 2001 August; 21(4): 440-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11476129
•
Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Author(s): Cochrane Database Syst Rev. 2002;(2):CD002852 Source: Archives of General Psychiatry. 2001 October; 58(10): 965-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076456
•
Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Author(s): Volavka J, Czobor P, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Cooper TB, Chakos M, Lieberman JA. Source: The American Journal of Psychiatry. 2002 February; 159(2): 255-62. Erratum In: Am J Psychiatry 2002 December; 159(12): 2132. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823268
•
Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Author(s): Sachs GS, Grossman F, Ghaemi SN, Okamoto A, Bowden CL. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1146-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091192
•
Comment: risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine. Author(s): Lu ML, Shen WW. Source: The Annals of Pharmacotherapy. 2002 July-August; 36(7-8): 1292; Author Reply 1292-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12086567
•
Comments on "Hypotension associated with intravenous haloperidol and imipenem. Author(s): Hauben M. Source: Journal of Clinical Psychopharmacology. 2001 June; 21(3): 345-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386502
Studies
57
•
Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. Author(s): Keefe RS, Seidman LJ, Christensen BK, Hamer RM, Sharma T, Sitskoorn MM, Lewine RR, Yurgelun-Todd DA, Gur RC, Tohen M, Tollefson GD, Sanger TM, Lieberman JA. Source: The American Journal of Psychiatry. 2004 June; 161(6): 985-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15169686
•
Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Author(s): Lieberman JA, Tollefson G, Tohen M, Green AI, Gur RE, Kahn R, McEvoy J, Perkins D, Sharma T, Zipursky R, Wei H, Hamer RM; HGDH Study Group. Source: The American Journal of Psychiatry. 2003 August; 160(8): 1396-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900300
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Comparative study of the effectiveness of zuclopenthixol acetate and haloperidol in acutely disturbed psychotic patients. Author(s): Taymeeyapradit U, Kuasirikul S. Source: J Med Assoc Thai. 2002 December; 85(12): 1301-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678168
•
Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia. Author(s): Paquet F, Soucy JP, Stip E, Levesque M, Elie A, Bedard MA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2004 Winter; 16(1): 47-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990759
•
Comparison of clozapine and haloperidol on some autonomic and psychomotor functions, and on serum prolactin concentration, in healthy subjects. Author(s): Pretorius JL, Phillips M, Langley RW, Szabadi E, Bradshaw CM. Source: British Journal of Clinical Pharmacology. 2001 September; 52(3): 322-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560566
•
Comparison of prolactin concentrations between haloperidol and bromperidol treatments in schizophrenic patients. Author(s): Yasui-Furukori N, Kondo T, Suzuki A, Mihara K, Kaneko S, Otani K. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 April; 26(3): 575-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999910
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Comparison of prolactin concentrations between haloperidol and risperidone treatments in the same female patients with schizophrenia. Author(s): Yasui-Furukori N, Kondo T, Suzuki A, Mihara K, Kaneko S. Source: Psychopharmacology. 2002 June; 162(1): 63-6. Epub 2002 April 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12107619
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Comparison of the efficacy of carbamazepine, haloperidol and valproic acid in the treatment of children with Sydenham's chorea: clinical follow-up of 18 patients. Author(s): Pena J, Mora E, Cardozo J, Molina O, Montiel C. Source: Arquivos De Neuro-Psiquiatria. 2002 June; 60(2-B): 374-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131934
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Compatibility of haloperidol and hyoscine-N-butyl bromide in mixtures for subcutaneous infusion to cancer patients in palliative care. Author(s): Barcia E, Reyes R, Luz Azuara M, Sanchez Y, Negro S. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 February; 11(2): 107-13. Epub 2003 January 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560939
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Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine. Author(s): Alfaro CL, Wudarsky M, Nicolson R, Gochman P, Sporn A, Lenane M, Rapoport JL. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Summer; 12(2): 8391. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12188977
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Delayed onset of oculogyric crisis and torticollis with intramuscular haloperidol. Author(s): Jhee SS, Zarotsky V, Mohaupt SM, Yones CL, Sims SJ. Source: The Annals of Pharmacotherapy. 2003 October; 37(10): 1434-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519055
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Delayed reactivation of haloperidol induced photosensitive dermatitis by methotrexate. Author(s): Thami GP, Kaur S, Kanwar AJ. Source: Postgraduate Medical Journal. 2002 February; 78(916): 116-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807213
•
Depot haloperidol decanoate for schizophrenia. Author(s): Quraishi S, David A. Source: Cochrane Database Syst Rev. 2000; (2): Cd001361. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796438
Studies
59
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Design, synthesis, and evaluation of metabolism-based analogues of haloperidol incapable of forming MPP+-like species. Author(s): Lyles-Eggleston M, Altundas R, Xia J, Sikazwe DM, Fan P, Yang Q, Li S, Zhang W, Zhu X, Schmidt AW, Vanase-Frawley M, Shrihkande A, Villalobos A, Borne RF, Ablordeppey SY. Source: Journal of Medicinal Chemistry. 2004 January 29; 47(3): 497-508. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736232
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Detection and mapping of quantitative trait loci for haloperidol-induced catalepsy in a C57BL/6J x DBA/2J F2 intercross. Author(s): Patel NV, Hitzemann RJ. Source: Behavior Genetics. 1999 September; 29(5): 303-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765558
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Determination of 1-methyl-1,2,3,4-tetrahydroisoquinoline in mouse brain after treatment with haloperidol by gas chromatography-selected ion monitoring. Author(s): Igarashi K, Sugiyama Y, Kasuya F, Saiki K, Yamakawa T, Ohata S. Source: J Chromatogr B Biomed Sci Appl. 1999 August 6; 731(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10491989
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Determining the optimal dose of haloperidol in first-episode psychosis. Author(s): Oosthuizen P, Emsley RA, Turner J, Keyter N. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11769818
•
Differences in haloperidol epidemiologic pharmacokinetic studies. Author(s): Jann MW, Chang WH, Lane HY. Source: Journal of Clinical Psychopharmacology. 2001 December; 21(6): 628-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11763020
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Differential effects of the antipsychotics haloperidol and clozapine on G protein measures in mononuclear leukocytes of patients with schizophrenia. Author(s): Avissar S, Roitman G, Schreiber G. Source: Cellular and Molecular Neurobiology. 2001 December; 21(6): 799-811. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12043849
•
Disposition of haloperidol pyridinium and reduced haloperidol pyridinium in schizophrenic patients: no relationship with clinical variables during short-term treatment. Author(s): Ulrich S, Neuhof S, Braun V, Danos P, Pester U, Hoy L. Source: Journal of Clinical Psychopharmacology. 2000 April; 20(2): 210-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770460
60
Haloperidol
•
Divalproex sodium augmentation of haloperidol in hospitalized patients with schizophrenia: clinical and economic implications. Author(s): Wassef AA, Hafiz NG, Hampton D, Molloy M. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11199943
•
Does a glutamate receptor blocker (Caroverine) enhance haloperidol in the treatment of schizophrenia? Author(s): Konig P, Conca A, Lugmayer B. Source: Neuropsychobiology. 1999 September; 40(3): 140-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10494049
•
Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia? Author(s): Sultzer DL, Gray KF, Gunay I, Wheatley MV, Mahler ME. Source: Journal of the American Geriatrics Society. 2001 October; 49(10): 1294-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11890487
•
Does cognitive function improve with quetiapine in comparison to haloperidol? Author(s): Velligan DI, Newcomer J, Pultz J, Csernansky J, Hoff AL, Mahurin R, Miller AL. Source: Schizophrenia Research. 2002 January 15; 53(3): 239-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11738537
•
Dopamine receptor responsivity in schizophrenic patients before and after switch from haloperidol to risperidone. Author(s): Markianos M, Hatzimanolis J, Lykouras L. Source: Psychiatry Research. 1999 December 20; 89(2): 115-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10646830
•
Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. Author(s): Robinson KA. Source: Clinical Therapeutics. 2000 November; 22(11): 1375-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11117662
•
Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina. Author(s): Sacristan JA, Gomez JC, Montejo AL, Vieta E, Gregor KJ. Source: Clinical Therapeutics. 2000 May; 22(5): 583-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10868556
Studies
61
•
Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment. Author(s): Allain H, Dautzenberg PH, Maurer K, Schuck S, Bonhomme D, Gerard D. Source: Psychopharmacology. 2000 March; 148(4): 361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10928308
•
Double-blind olanzapine vs. haloperidol D2 dopamine receptor blockade in schizophrenic patients: a baseline-endpoint. Author(s): Bernardo M, Parellada E, Lomena F, Catafau AM, Font M, Gomez JC, LopezCarrero C, Gutierrez F, Pavia J, Salamero M. Source: Psychiatry Research. 2001 August 25; 107(2): 87-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530275
•
Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Author(s): Wright P, Birkett M, David SR, Meehan K, Ferchland I, Alaka KJ, Saunders JC, Krueger J, Bradley P, San L, Bernardo M, Reinstein M, Breier A. Source: The American Journal of Psychiatry. 2001 July; 158(7): 1149-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11431240
•
EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects. Author(s): Amann BL, Pogarell O, Mergl R, Juckel G, Grunze H, Mulert C, Hegerl U. Source: Human Psychopharmacology. 2003 December; 18(8): 641-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696024
•
Effect of cetrimide and ascorbic acid on in vitro human skin permeation of haloperidol. Author(s): Vaddi HK, Wang LZ, Ho PC, Chan YW, Chan SY. Source: Chemical & Pharmaceutical Bulletin. 2001 November; 49(11): 1395-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11724228
•
Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population. Author(s): Someya T, Shimoda K, Suzuki Y, Sato S, Kawashima Y, Hirokane G, Morita S, Yokono A, Takahashi S. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 August; 28(8): 1501-5. Epub 2003 June 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784098
62
Haloperidol
•
Effect of risperidone on sleep in schizophrenia: a comparison with haloperidol. Author(s): Yamashita H, Morinobu S, Yamawaki S, Horiguchi J, Nagao M. Source: Psychiatry Research. 2002 March 15; 109(2): 137-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927138
•
Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. Author(s): Rosenheck R, Perlick D, Bingham S, Liu-Mares W, Collins J, Warren S, Leslie D, Allan E, Campbell EC, Caroff S, Corwin J, Davis L, Douyon R, Dunn L, Evans D, Frecska E, Grabowski J, Graeber D, Herz L, Kwon K, Lawson W, Mena F, Sheikh J, Smelson D, Smith-Gamble V; Department of Veterans Affairs Cooperative Study Group on the Cost-Effectiveness of Olanzapine. Source: Jama : the Journal of the American Medical Association. 2003 November 26; 290(20): 2693-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645311
•
Effectiveness of antipsychotic treatments for schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol. Author(s): Dossenbach M, Erol A, el Mahfoud Kessaci M, Shaheen MO, Sunbol MM, Boland J, Hodge A, O'Halloran RA, Bitter I; IC-SOHO Study Group. Source: The Journal of Clinical Psychiatry. 2004 March; 65(3): 312-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096069
•
Effects of age and the CYP2D6*10 allele on the plasma haloperidol concentration/dose ratio. Author(s): Ohara K, Tanabu S, Ishibashi K, Ikemoto K, Yoshida K, Shibuya H. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 347-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691769
•
Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Author(s): Citrome L, Volavka J, Czobor P, Sheitman B, Lindenmayer JP, McEvoy J, Cooper TB, Chakos M, Lieberman JA. Source: Psychiatric Services (Washington, D.C.). 2001 November; 52(11): 1510-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11684748
•
Effects of haloperidol and atypical neuroleptics on psychomotor performance and driving ability in schizophrenic patients. Results from an experimental study. Author(s): Kagerer S, Winter C, Moller HJ, Soyka M. Source: Neuropsychobiology. 2003; 47(4): 212-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824745
Studies
63
•
Effects of smoking and cytochrome P450 2D6*10 allele on the plasma haloperidol concentration/dose ratio. Author(s): Ohara K, Tanabu S, Yoshida K, Ishibashi K, Ikemoto K, Shibuya H. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 September; 27(6): 945-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499311
•
Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. Author(s): Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, Ali MW. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 763-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12363115
•
Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Author(s): Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, Archibald D, Ingenito G, Marcus R, Pigott T. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2003 December; 6(4): 325-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609439
•
Efficacy and safety of zotepine for the treatment of Taiwanese schizophrenic patients: a double-blind comparison with haloperidol. Author(s): Hwang TJ, Lin SK, Lin HN. Source: J Formos Med Assoc. 2001 December; 100(12): 811-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11802520
•
Emotion perception in schizophrenia: an eye movement study comparing the effectiveness of risperidone vs. haloperidol. Author(s): Williams LM, Loughland CM, Green MJ, Harris AW, Gordon E. Source: Psychiatry Research. 2003 August 30; 120(1): 13-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500110
•
Ethnicity and prescription patterns for haloperidol, risperidone, and olanzapine. Author(s): Opolka JL, Rascati KL, Brown CM, Gibson PJ. Source: Psychiatric Services (Washington, D.C.). 2004 February; 55(2): 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762239
64
Haloperidol
•
Extrapyramidal symptom profiles assessed with the Drug-Induced Extrapyramidal Symptom Scale: comparison with Western scales in the clinical double-blind studies of schizophrenic patients treated with either olanzapine or haloperidol. Author(s): Inada T, Beasley CM Jr, Tanaka Y, Walker DJ. Source: International Clinical Psychopharmacology. 2003 January; 18(1): 39-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490774
•
Extrapyramidal symptom profiles in Japanese patients with schizophrenia treated with olanzapine or haloperidol. Author(s): Inada T, Yagi G, Miura S. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 227-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223254
•
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
•
Factors affecting serum haloperidol level assessed by longitudinal therapeutic monitoring. Author(s): Fukuda R. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2000 November; 24(8): 1299-318. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11125855
•
Factors affecting the clinical response to haloperidol therapy in schizophrenia. Author(s): Bareggi SR, Mauri M, Cavallaro R, Regazzetti MG, Moro AR. Source: Clinical Neuropharmacology. 1990; 13 Suppl 1: S29-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2379182
•
Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. Author(s): Basson BR, Kinon BJ, Taylor CC, Szymanski KA, Gilmore JA, Tollefson GD. Source: The Journal of Clinical Psychiatry. 2001 April; 62(4): 231-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11379836
Studies
65
•
Factors related to haloperidol response and dyskinesias in autistic children. Author(s): Locascio JJ, Malone RP, Small AM, Kafantaris V, Ernst M, Lynch NS, Overall JE, Campbell M. Source: Psychopharmacology Bulletin. 1991; 27(2): 119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1924657
•
Failure of haloperidol to alter gonadotropin release in Tourette's syndrome. Author(s): Sandyk R. Source: Journal of Clinical Psychopharmacology. 1989 February; 9(1): 60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2496150
•
Fatal hyperthermia in a quadriplegic man. Possible evidence for a peripheral action of haloperidol in neuroleptic malignant syndrome. Author(s): Downey RJ, Downey JA, Newhouse E, Weissman C. Source: Chest. 1992 June; 101(6): 1728-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1600803
•
First-episode neuroleptic-free schizophrenics: concentrations of monoamines and their metabolites in plasma and their correlations with clinical responses to haloperidol treatment. Author(s): Nagaoka S, Iwamoto N, Arai H. Source: Biological Psychiatry. 1997 April 15; 41(8): 857-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9099412
•
Fluoxetine augmentation of haloperidol in chronic schizophrenia. Author(s): Shim JC, Kelly DL, Kim YH, Yoon YR, Park JH, Shin JG, Conley RR. Source: Journal of Clinical Psychopharmacology. 2003 October; 23(5): 520-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520132
•
Fluvoxamine dose-dependent interaction with haloperidol and the effects on negative symptoms in schizophrenia. Author(s): Yasui-Furukori N, Kondo T, Mihara K, Inoue Y, Kaneko S. Source: Psychopharmacology. 2004 January; 171(2): 223-7. Epub 2003 September 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955290
•
Formation of pyridinium species of haloperidol in human liver and brain. Author(s): Eyles DW, McGrath JJ, Pond SM. Source: Psychopharmacology. 1996 June; 125(3): 214-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8815956
66
Haloperidol
•
Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study. Author(s): Bobes J, Garc A-Portilla MP, Rejas J, Hern Ndez G, Garcia-Garcia M, RicoVillademoros F, Porras A. Source: Journal of Sex & Marital Therapy. 2003 March-April; 29(2): 125-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623765
•
Frequency of sexual dysfunctions in patients with schizophrenia on haloperidol, clozapine or risperidone. Author(s): Mullen B, Brar JS, Vagnucci AH, Ganguli R. Source: Schizophrenia Research. 2001 March 1; 48(1): 155-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345946
•
Full remission of panic attacks in a schizophrenic patient after switching from haloperidol to risperidone. Author(s): Takahashi H, Higuchi H, Shimizu T. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2001 Winter; 13(1): 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11207340
•
Functional effects of antipsychotic drugs: comparing clozapine with haloperidol. Author(s): Lahti AC, Holcomb HH, Weiler MA, Medoff DR, Tamminga CA. Source: Biological Psychiatry. 2003 April 1; 53(7): 601-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679238
•
Functional outcomes in schizophrenia: a comparison of olanzapine and haloperidol in a European sample. Author(s): Hamilton SH, Edgell ET, Revicki DA, Breier A. Source: International Clinical Psychopharmacology. 2000 September; 15(5): 245-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10993126
•
Functional sites of neuroleptic drug action in the human brain: PET/FDG studies with and without haloperidol. Author(s): Holcomb HH, Cascella NG, Thaker GK, Medoff DR, Dannals RF, Tamminga CA. Source: The American Journal of Psychiatry. 1996 January; 153(1): 41-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8540590
Studies
67
•
Further characterisation of the interaction of haloperidol metabolites with neurotransmitter transporters in rat neuronal cultures and in transfected COS-7 cells. Author(s): Siebert GA, Pond SM, Bryan-Lluka LJ. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2000 March; 361(3): 255-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10731037
•
Further evidence of a dose-response threshold for haloperidol in psychosis. Author(s): Stone CK, Garve DL, Griffith J, Hirschowitz J, Bennett J. Source: The American Journal of Psychiatry. 1995 August; 152(8): 1210-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7625474
•
Further observations on vesicourethral dopamine receptors--a urodynamic study with haloperidol. Author(s): Vaidyanathan S, Rao MS, Bapna BC, Sharma PL, Chary KS, Swamy RP. Source: Ann Clin Res. 1980 April; 12(2): 49-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7447363
•
Gas chromatographic--mass spectrometric determination of haloperidol in plasma. Application to pharmacokinetics. Author(s): Haring N, Salama Z, Todesko L, Jaeger H. Source: Arzneimittel-Forschung. 1987 December; 37(12): 1402-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3449072
•
Gas-chromatographic measurement of haloperidol in plasma. Author(s): Franklin M. Source: Clinical Chemistry. 1980 August; 26(9): 1367-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7398059
•
Generalization of serotonin (5-HT)1A agonists and the antipsychotics, clozapine, ziprasidone and S16924, but not haloperidol, to the discriminative stimuli elicited by PD128,907 and 7-OH-DPAT. Author(s): Dekeyne A, Rivet JM, Gobert A, Millan MJ. Source: Neuropharmacology. 2001 June; 40(7): 899-910. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11378160
•
Genetic association between cytochrome P-450 2D6 gene polymorphism and plasma concentration of haloperidol in Japanese schizophrenics. Author(s): Shibata N, Ohnuma T, Baba H, Shimada H, Takahashi T, Arai H. Source: Psychiatric Genetics. 1999 September; 9(3): 145-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10551545
68
Haloperidol
•
Genetic factors in the metabolism of haloperidol. Author(s): Llerena A, Dahl ML, Ekqvist B, Bertilsson L. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 84A-85A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1499007
•
Glucose administration does not modulate prolactin response to exercise, TRH or haloperidol injection. Author(s): Vigas M, Jezova D. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 1994; 43(5): 293-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7711007
•
Glucose potentiates haloperidol-induced catalepsy. Author(s): Saller CF, Kopin IJ. Source: Life Sciences. 1981 November 30; 29(22): 2337-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7198706
•
Gonadal axis hormones in male schizophrenic patients during treatment with haloperidol and after switch to risperidone. Author(s): Markianos M, Hatzimanolis J, Lykouras L. Source: Psychopharmacology. 1999 April; 143(3): 270-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10353429
•
Haloperidol and benztropine interaction presenting as acute intestinal pseudoobstruction. Author(s): Sheikh RA, Prindiville T, Yasmeen S. Source: The American Journal of Gastroenterology. 2001 March; 96(3): 934-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11280595
•
Haloperidol blood levels in acute mania with psychosis. Author(s): Chou JC, Czobor P, Dacpano G, Richardson N, Tuma I, Trujillo M, Cooper TB, Volavka J. Source: Journal of Clinical Psychopharmacology. 2001 August; 21(4): 445-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11476130
•
Haloperidol decanoate in children. Author(s): Alessi N, Alkhouri I, Fluent T, Quinlan P, Williams K. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 August; 40(8): 865-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501680
Studies
69
•
Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease. Author(s): Wirz-Justice A, Werth E, Savaskan E, Knoblauch V, Gasio PF, Muller-Spahn F. Source: Alzheimer Disease and Associated Disorders. 2000 October-December; 14(4): 212-5. Erratum In: Alzheimer Dis Assoc Disord 2001 April-June; 15(2): 101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186599
•
Haloperidol dose for the acute phase of schizophrenia. Author(s): Waraich PS, Adams CE, Roque M, Hamill KM, Marti J. Source: Cochrane Database Syst Rev. 2002; (3): Cd001951. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137638
•
Haloperidol for agitation in dementia. Author(s): Lonergan E, Luxenberg J, Colford J. Source: Cochrane Database Syst Rev. 2002; (2): Cd002852. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076456
•
Haloperidol for agitation in dementia. Author(s): Lonergan E, Luxenberg J, Colford J. Source: Cochrane Database Syst Rev. 2001; (4): Cd002852. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687166
•
Haloperidol in palliative care. Author(s): Vella-Brincat J, Macleod AD. Source: Palliative Medicine. 2004 April; 18(3): 195-201. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15198132
•
Haloperidol overdose during pregnancy. Author(s): Hansen LM, Megerian G, Donnenfeld AE. Source: Obstetrics and Gynecology. 1997 October; 90(4 Pt 2): 659-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11770584
•
Haloperidol plasma concentration in Japanese psychiatric subjects with gene duplication of CYP2D6. Author(s): Ohnuma T, Shibata N, Matsubara Y, Arai H. Source: British Journal of Clinical Pharmacology. 2003 September; 56(3): 315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919180
70
Haloperidol
•
Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes. Author(s): Brauer LH, Cramblett MJ, Paxton DA, Rose JE. Source: Psychopharmacology. 2001 December; 159(1): 31-7. Epub 2001 September 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11797066
•
Haloperidol reduces stimulant and reinforcing effects of ethanol in social drinkers. Author(s): Enggasser JL, de Wit H. Source: Alcoholism, Clinical and Experimental Research. 2001 October; 25(10): 1448-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11696664
•
Haloperidol should be used sparingly. Author(s): Skrobik Y. Source: Critical Care Medicine. 2002 November; 30(11): 2613-4; Author Reply 2614. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441793
•
Haloperidol versus placebo for schizophrenia. Author(s): Joy CB, Adams CE, Lawrie SM. Source: Cochrane Database Syst Rev. 2001; (2): Cd003082. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406070
•
Haloperidol, midazolam and intravenous sedation. Author(s): Ryan CJ. Source: The Australian and New Zealand Journal of Psychiatry. 1999 December; 33(6): 942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10619226
•
Haloperidol-induced impotence improved by switching to olanzapine. Author(s): Tsai SJ, Hong CJ. Source: General Hospital Psychiatry. 2000 September-October; 22(5): 391-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11203037
•
Haloperidol-induced rhabdomyolysis without neuroleptic malignant syndrome in a handicapped child. Author(s): Yoshikawa H, Watanabe T, Abe T, Oda Y, Ozawa K. Source: Brain & Development. 2000 June; 22(4): 256-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10838114
Studies
71
•
High-dose treatment with haloperidol: the effect of dose reduction. Author(s): Volavka J, Cooper TB, Czobor P, Lindenmayer JP, Citrome LL, Mohr P, Bark N. Source: Journal of Clinical Psychopharmacology. 2000 April; 20(2): 252-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770466
•
Histamine H1-receptor antagonists, promethazine and homochlorcyclizine, increase the steady-state plasma concentrations of haloperidol and reduced haloperidol. Author(s): Suzuki A, Yasui-Furukori N, Mihara K, Kondo T, Furukori H, Inoue Y, Kaneko S, Otani K. Source: Therapeutic Drug Monitoring. 2003 April; 25(2): 192-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657913
•
IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol. Author(s): Kufferle B, Tauscher J, Asenbaum S, Vesely C, Podreka I, Brucke T, Kasper S. Source: Psychopharmacology. 1997 October; 133(4): 323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9372530
•
Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Author(s): Song C, Lin A, Kenis G, Bosmans E, Maes M. Source: Schizophrenia Research. 2000 April 7; 42(2): 157-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10742653
•
Impact of risperidone versus haloperidol on activities of daily living in the treatment of refractory schizophrenia. Author(s): Liberman RP, Gutkind D, Mintz J, Green M, Marshall BD Jr, Robertson MJ, Hayden J. Source: Comprehensive Psychiatry. 2002 November-December; 43(6): 469-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439835
•
Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol. Author(s): Suzuki Y, Someya T, Shimoda K, Hirokane G, Morita S, Yokono A, Inoue Y, Takahashi S. Source: Therapeutic Drug Monitoring. 2001 August; 23(4): 363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11477317
72
Haloperidol
•
In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes. Author(s): Fang J, McKay G, Song J, Remillrd A, Li X, Midha K. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 December; 29(12): 1638-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717183
•
In vitro study on the involvement of CYP1A2, CYP2D6 and CYP3A4 in the metabolism of haloperidol and reduced haloperidol. Author(s): Pan L, Belpaire FM. Source: European Journal of Clinical Pharmacology. 1999 October; 55(8): 599-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541779
•
In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol. Author(s): Tauscher J, Kufferle B, Asenbaum S, Fischer P, Pezawas L, Barnas C, Tauscher-Wisniewski S, Brucke T, Kasper S. Source: Psychopharmacology. 1999 January; 141(2): 175-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9952042
•
Incidence of tardive dyskinesia in first-episode psychosis patients treated with lowdose haloperidol. Author(s): Oosthuizen PP, Emsley RA, Maritz JS, Turner JA, Keyter N. Source: The Journal of Clinical Psychiatry. 2003 September; 64(9): 1075-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628983
•
Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Author(s): Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R. Source: The American Journal of Psychiatry. 2001 February; 158(2): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11156818
•
Influence of haloperidol on the relationship of frontal lobe function to psychomotor poverty and disorganization syndromes. Author(s): Allen DN, Anastasiou A, Goldstein G, Gilbertson M, van Kammen DP. Source: Psychiatry Research. 2000 February 14; 93(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10699226
•
Interaction between olanzapine and haloperidol. Author(s): Gomberg RF. Source: Journal of Clinical Psychopharmacology. 1999 June; 19(3): 272-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10350035
Studies
73
•
Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Author(s): Krystal JH, D'Souza DC, Karper LP, Bennett A, Abi-Dargham A, Abi-Saab D, Cassello K, Bowers MB Jr, Vegso S, Heninger GR, Charney DS. Source: Psychopharmacology. 1999 July; 145(2): 193-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463321
•
Interindividual variation of plasma haloperidol concentrations and the impact of concomitant medications: the analysis of therapeutic drug monitoring data. Author(s): Hirokane G, Someya T, Takahashi S, Morita S, Shimoda K. Source: Therapeutic Drug Monitoring. 1999 February; 21(1): 82-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051058
•
Interindividual variation of serum haloperidol concentrations in Japanese patients-clinical considerations on steady-state serum level-dose ratios. Author(s): Yukawa E, Ichimaru R, Maki T, Matsunaga K, Anai M, Yukawa M, Higuchi S, Goto Y. Source: Journal of Clinical Pharmacy and Therapeutics. 2003 April; 28(2): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12713605
•
Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. Author(s): Dorevitch A, Katz N, Zemishlany Z, Aizenberg D, Weizman A. Source: The American Journal of Psychiatry. 1999 January; 156(1): 142-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9892313
•
Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia: antipsychotic efficacy and extrapyramidal safety during the first 24 hours of treatment. Author(s): Wright P, Lindborg SR, Birkett M, Meehan K, Jones B, Alaka K, FerchlandHowe I, Pickard A, Taylor CC, Roth J, Battaglia J, Bitter I, Chouinard G, Morris PL, Breier A. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 December; 48(11): 716-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14733451
•
Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group. Author(s): Brook S, Lucey JV, Gunn KP. Source: The Journal of Clinical Psychiatry. 2000 December; 61(12): 933-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11206599
74
Haloperidol
•
Intravenous haloperidol. Author(s): Arrants J. Source: Critical Care Nurse. 2001 June; 21(3): 19-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858672
•
In-vitro characterization of the cytochrome P450 isoenzymes involved in the back oxidation and N-dealkylation of reduced haloperidol. Author(s): Pan LP, De Vriendt C, Belpaire FM. Source: Pharmacogenetics. 1998 October; 8(5): 383-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825830
•
In-vitro immunomodulatory effects of haloperidol and perazine in schizophrenia. Author(s): Kowalski J, Blada P, Kucia K, Lawniczek T, Madej A, Belowski D, Herman ZS. Source: World J Biol Psychiatry. 2000 October; 1(4): 190-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607215
•
Ketone reductase activity and reduced haloperidol/haloperidol ratios in haloperidoltreated schizophrenic patients. Author(s): Huang HF, Jann MW, Tseng YT, Chung MC, Chien CP, Chang WH. Source: Psychiatry Research. 1995 July 28; 57(2): 101-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7480377
•
Kinetic analysis of central nervous system supersensitivity induced in rats by longterm haloperidol administration. I. pA2 determination. Author(s): Palermo-Neto J, Bernardi MM, Saban R. Source: Pharmacology. 1984; 28(4): 203-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6539476
•
Kinetics and clinical evaluation of haloperidol decanoate loading dose regimen. Author(s): Ereshefsky L, Saklad SR, Tran-Johnson T, Toney G, Lyman RC, Davis CM. Source: Psychopharmacology Bulletin. 1990; 26(1): 108-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2371365
•
Lack of correlation between the steady-state plasma concentrations of haloperidol and risperidone. Author(s): Yasui-Furukori N, Kondo T, Mihara K, Suzuki A, Inoue Y, De Vries R, Kaneko S. Source: Journal of Clinical Pharmacology. 2002 October; 42(10): 1083-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362921
Studies
75
•
Lack of evidence for in vivo interaction of steroids with haloperidol-sensitive sigma (sigma H) binding sites in brain and spleen. Author(s): Schwarz S, Pohl P. Source: Prog Clin Biol Res. 1990; 328: 17-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2154774
•
Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia. Author(s): Shimoda K, Someya T, Morita S, Hirokane G, Yokono A, Takahashi S, Okawa M. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 February; 26(2): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817502
•
LC-MS-MS analysis of the neuroleptics clozapine, flupentixol, haloperidol, penfluridol, thioridazine, and zuclopenthixol in hair obtained from psychiatric patients. Author(s): Weinmann W, Muller C, Vogt S, Frei A. Source: Journal of Analytical Toxicology. 2002 July-August; 26(5): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166818
•
Life-threatening ventricular arrhythmia (torsades de pointes) after haloperidol overdose. Author(s): Henderson RA, Lane S, Henry JA. Source: Human & Experimental Toxicology. 1991 January; 10(1): 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1673626
•
Liquid chromatographic determination of reduced haloperidol and haloperidol concentrations in packed red blood cells from humans. Author(s): Vatassery GT, Herzan LA, Dysken MW. Source: Journal of Analytical Toxicology. 1990 January-February; 14(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2314059
•
Liquid chromatographic-mass spectrometric determination of haloperidol and its metabolites in human plasma and urine. Author(s): Arinobu T, Hattori H, Iwai M, Ishii A, Kumazawa T, Suzuki O, Seno H. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 August 25; 776(1): 107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127331
76
Haloperidol
•
Lithium and haloperidol treatments differently affect the mononuclear leukocyte Galphas protein levels in bipolar affective disorder. Author(s): Karege F, Golaz J, Schwald M, Malafosse A. Source: Neuropsychobiology. 1999 May; 39(4): 181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10343182
•
Lithium combined with carbamazepine or haloperidol in the treatment of mania. Author(s): Small JG, Klapper MH, Marhenke JD, Milstein V, Woodham GC, Kellams JJ. Source: Psychopharmacology Bulletin. 1995; 31(2): 265-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7491378
•
Lithium combined with haloperidol in schizophrenic patients. Author(s): Lerner Y, Mintzer Y, Schestatzky M. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1988 September; 153: 359-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3150693
•
Longitudinal study of the effect, tolerance and undesired side effects of injection haloperidol decanoate applied in different psychiatric indications. Author(s): Zbytovsky J, Zapletalek M. Source: Act Nerv Super (Praha). 1989 December; 31(4): 266-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2638106
•
Long-term efficacy and safety comparison of sertindole and haloperidol in the treatment of schizophrenia. The Sertindole Study Group. Author(s): Daniel DG, Wozniak P, Mack RJ, McCarthy BG. Source: Psychopharmacology Bulletin. 1998; 34(1): 61-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9564200
•
Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration. Author(s): Perry R, Campbell M, Adams P, Lynch N, Spencer EK, Curren EL, Overall JE. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1989 January; 28(1): 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2914841
•
Long-term haloperidol treatment and factors affecting the activity of striatal tyrosine hydroxylase. Author(s): Lovenberg W, Alphs L, Pradhan S, Bruckwick E, Levine R. Source: Adv Biochem Psychopharmacol. 1980; 24: 9-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6105810
Studies
77
•
Low- and standard-dose depot haloperidol combined with targeted oral neuroleptics. Author(s): Huttunen MO, Tuhkanen H, Haavisto E, Nyholm R, Pitkanen M, Raitasuo V, Romanov M. Source: Psychiatric Services (Washington, D.C.). 1996 January; 47(1): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8925352
•
Low plasma reduced haloperidol/haloperidol ratios in Chinese patients. Author(s): Chang WH, Chen TY, Lee CF, Hu WH, Yeh EK. Source: Biological Psychiatry. 1987 November; 22(11): 1406-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3663790
•
Lower CSF orexin A (hypocretin-1) levels in patients with schizophrenia treated with haloperidol compared to unmedicated subjects. Author(s): Dalal MA, Schuld A, Pollmacher T. Source: Molecular Psychiatry. 2003 October; 8(10): 836-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515133
•
Lower incidence of tardive dyskinesia with risperidone compared with haloperidol in older patients. Author(s): Jeste DV, Lacro JP, Bailey A, Rockwell E, Harris MJ, Caligiuri MP. Source: Journal of the American Geriatrics Society. 1999 June; 47(6): 716-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10366172
•
Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients. Author(s): Shimoda K, Someya T, Morita S, Hirokane G, Noguchi T, Yokono A, Shibasaki M, Takahashi S. Source: Therapeutic Drug Monitoring. 1999 June; 21(3): 293-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10365639
•
Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. Author(s): Marder SR, Glynn SM, Wirshing WC, Wirshing DA, Ross D, Widmark C, Mintz J, Liberman RP, Blair KE. Source: The American Journal of Psychiatry. 2003 August; 160(8): 1405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900301
•
Marked improvement of tardive dystonia after replacing haloperidol with risperidone in a schizophrenic patient. Author(s): Yoshida K, Higuchi H, Hishikawa Y. Source: Clinical Neuropharmacology. 1998 January-February; 21(1): 68-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579290
78
Haloperidol
•
Maternal haloperidol therapy associated with dyskinesia in a newborn. Author(s): Collins KO, Comer JB. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 November 1; 60(21): 2253-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619120
•
Medication continuation and compliance: a comparison of patients treated with clozapine and haloperidol. Author(s): Rosenheck R, Chang S, Choe Y, Cramer J, Xu W, Thomas J, Henderson W, Charney D. Source: The Journal of Clinical Psychiatry. 2000 May; 61(5): 382-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10847315
•
Memory-based comparison process not attenuated by haloperidol: a combined MEG and EEG study. Author(s): Pekkone E, Hirvonen J, Ahveninen J, Kahkonen S, Kaakkola S, Huttunen J, Jaaskelainen IP. Source: Neuroreport. 2002 January 21; 13(1): 177-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11924884
•
Metabolism of haloperidol and its tetrahydropyridine dehydration product HPTP. Author(s): Usuki E, Van der Schyf CJ, Castagnoli N Jr. Source: Drug Metabolism Reviews. 1998 November; 30(4): 809-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9844810
•
Metabolism of haloperidol to pyridinium species in patients receiving high doses intravenously: is HPTP an intermediate? Author(s): Avent KM, Riker RR, Fraser GL, Van der Schyf CJ, Usuki E, Pond SM. Source: Life Sciences. 1997; 61(24): 2383-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399630
•
Minimum effective doses of haloperidol for the treatment of first psychotic episode: a comparative study with risperidone and olanzapine. Author(s): Apiquian R, Fresan A, Herrera K, Ulloa RE, Loyzaga C, de la FuenteSandoval C, Gutierrez D, Nicolini H. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2003 December; 6(4): 403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604455
Studies
79
•
Modulating sensory gating in healthy volunteers: the effects of ketamine and haloperidol. Author(s): Oranje B, Gispen-de Wied CC, Verbaten MN, Kahn RS. Source: Biological Psychiatry. 2002 November 1; 52(9): 887-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399142
•
Modulation of the N-methyl-D-aspartate receptor by haloperidol: NR2B-specific interactions. Author(s): Gallagher MJ, Huang H, Lynch DR. Source: Journal of Neurochemistry. 1998 May; 70(5): 2120-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9572299
•
Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Author(s): Arvanitis LA, Miller BG. Source: Biological Psychiatry. 1997 August 15; 42(4): 233-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9270900
•
Myoclonic and generalized tonic clonic seizures during combined treatment with low doses of clozapine and haloperidol. Author(s): Haberfellner EM. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 March; 17(1): 55-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918994
•
Nefazodone in psychotic unipolar and bipolar depression: a retrospective chart analysis and open prospective study on its efficacy and safety versus combined treatment with amitriptyline and haloperidol. Author(s): Grunze H, Marcuse A, Scharer LO, Born C, Walden J. Source: Neuropsychobiology. 2002; 46 Suppl 1: 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571431
•
Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Author(s): Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, Lindenmayer JP, Citrome L, McEvoy J, Kunz M, Chakos M, Cooper TB, Horowitz TL, Lieberman JA. Source: The American Journal of Psychiatry. 2002 June; 159(6): 1018-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042192
80
Haloperidol
•
Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol. Author(s): Markianos M, Hatzimanolis J, Lykouras L. Source: European Archives of Psychiatry and Clinical Neuroscience. 2001 June; 251(3): 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11697576
•
Neuroleptic malignant syndrome after addition of haloperidol to atypical antipsychotic. Author(s): Mujica R, Weiden P. Source: The American Journal of Psychiatry. 2001 April; 158(4): 650-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11282706
•
Neuroleptic malignant syndrome during a change from haloperidol to risperidone. Author(s): Reeves RR, Mack JE, Torres RA. Source: The Annals of Pharmacotherapy. 2001 June; 35(6): 698-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408988
•
Neuroleptic therapy influences basal ganglia activation: a functional magnetic resonance imaging study comparing controls to haloperidol- and olanzapine-treated inpatients. Author(s): Muller JL, Klein HE. Source: Psychiatry and Clinical Neurosciences. 2000 December; 54(6): 653-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145463
•
Neurologic side effects in neuroleptic-naive patients treated with haloperidol or risperidone. Author(s): Meibach RC. Source: Neurology. 2000 October 10; 55(7): 1069. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061283
•
Neurologic side effects in neuroleptic-naive patients treated with haloperidol or risperidone. Author(s): Windhaber J, Urbanits S, Grisold W. Source: Neurology. 2000 April 11; 54(7): 1543-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10751282
•
Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. Author(s): Purdon SE, Malla A, Labelle A, Lit W. Source: Journal of Psychiatry & Neuroscience : Jpn. 2001 March; 26(2): 137-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291531
Studies
81
•
Nicotine decreases bradykinesia-rigidity in haloperidol-treated patients with schizophrenia. Author(s): Yang YK, Nelson L, Kamaraju L, Wilson W, McEvoy JP. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 October; 27(4): 684-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377405
•
Olanzapine vs haloperidol for treatment of schizophrenia. Author(s): de Haan L, van Beveren N. Source: Jama : the Journal of the American Medical Association. 2004 March 3; 291(9): 1065; Author Reply 1065-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996769
•
Olanzapine vs haloperidol for treatment of schizophrenia. Author(s): Kunz M. Source: Jama : the Journal of the American Medical Association. 2004 March 3; 291(9): 1065; Author Reply 1065-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996768
•
Olanzapine vs haloperidol for treatment of schizophrenia. Author(s): Amin M, Shukla VS. Source: Jama : the Journal of the American Medical Association. 2004 March 3; 291(9): 1065; Author Reply 1065-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996767
•
Olanzapine vs haloperidol for treatment of schizophrenia. Author(s): Glazer WM. Source: Jama : the Journal of the American Medical Association. 2004 March 3; 291(9): 1064-5; Author Reply 1065-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996766
•
Olanzapine vs haloperidol for treatment of schizophrenia. Author(s): Volavka J, Citrome L. Source: Jama : the Journal of the American Medical Association. 2004 March 3; 291(9): 1064; Author Reply 1065-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996765
82
Haloperidol
•
Olanzapine vs haloperidol in geriatric schizophrenia: analysis of data from a doubleblind controlled trial. Author(s): Kennedy JS, Jeste D, Kaiser CJ, Golshan S, Maguire GA, Tollefson G, Sanger T, Bymaster FP, Kinon BJ, Dossenbach M, Gilmore JA, Breier A. Source: International Journal of Geriatric Psychiatry. 2003 November; 18(11): 1013-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618553
•
Olanzapine vs haloperidol: treating delirium in a critical care setting. Author(s): Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Source: Intensive Care Medicine. 2004 March; 30(3): 444-9. Epub 2003 December 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685663
•
Olanzapine, risperidone and haloperidol in the treatment of adolescent patients with schizophrenia. Author(s): Gothelf D, Apter A, Reidman J, Brand-Gothelf A, Bloch Y, Gal G, Kikinzon L, Tyano S, Weizman R, Ratzoni G. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 May; 110(5): 54560. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12721815
•
Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. Author(s): Volavka J, Czobor P, Nolan K, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Cooper TB, Lieberman JA. Source: Journal of Clinical Psychopharmacology. 2004 April; 24(2): 225-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15206671
•
Oxide terpenes as human skin penetration enhancers of haloperidol from ethanol and propylene glycol and their modes of action on stratum corneum. Author(s): Vaddi HK, Ho PC, Chan YW, Chan SY. Source: Biological & Pharmaceutical Bulletin. 2003 February; 26(2): 220-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576684
•
Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. Author(s): Desai M, Tanus-Santos JE, Li L, Gorski JC, Arefayene M, Liu Y, Desta Z, Flockhart DA. Source: The Pharmacogenomics Journal. 2003; 3(2): 105-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746736
Studies
83
•
Poor reliability of therapeutic drug monitoring data for haloperidol and bromperidol using enzyme immunoassay. Author(s): Yasui-Furukori N, Furukori H, Saito M, Inoue Y, Kaneko S, Tateishi T. Source: Therapeutic Drug Monitoring. 2003 December; 25(6): 709-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639057
•
Population pharmacokinetics of haloperidol using routine clinical pharmacokinetic data in Japanese patients. Author(s): Yukawa E, Hokazono T, Yukawa M, Ichimaru R, Maki T, Matsunaga K, Ohdo S, Anai M, Higuchi S, Goto Y. Source: Clinical Pharmacokinetics. 2002; 41(2): 153-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888334
•
Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hair: differential uptake of 3H-haloperidol by pigmentproducing compared to non-pigment-producing cell lines. Author(s): Potsch L, Emmerich P, Skopp G. Source: International Journal of Legal Medicine. 2002 February; 116(1): 58-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11924713
•
Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hairs: pigments as carriers for 3H-haloperidol in HaCaT/Sk-Mel1 co-cultures. Author(s): Potsch L, Emmerich P, Skopp G. Source: International Journal of Legal Medicine. 2002 February; 116(1): 12-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11924701
•
Procedural learning in schizophrenia after 6 months of double-blind treatment with olanzapine, risperidone, and haloperidol. Author(s): Purdon SE, Woodward N, Lindborg SR, Stip E. Source: Psychopharmacology. 2003 September; 169(3-4): 390-7. Epub 2003 June 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827347
•
Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. Author(s): Volavka J, Czobor P, Cooper TB, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Lieberman JA. Source: The Journal of Clinical Psychiatry. 2004 January; 65(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744169
84
Haloperidol
•
Prolactin responses to acute clomipramine and haloperidol of male schizophrenic patients in a drug-free state and after treatment with clozapine or with olanzapine. Author(s): Markianos M, Hatzimanolis J, Lykouras L, Christodoulou GN. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084414
•
Pro-Leu-glycinamide and its peptidomimetic, PAOPA, attenuate haloperidol induced vacuous chewing movements in rat: A model of human tardive dyskinesia. Author(s): Sharma S, Paladino P, Gabriele J, Saeedi H, Henry P, Chang M, Mishra RK, Johnson RL. Source: Peptides. 2003 February; 24(2): 313-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668218
•
QTc interval lengthening and debrisoquine metabolic ratio in psychiatric patients treated with oral haloperidol monotherapy. Author(s): LLerena A, Berecz R, de la Rubia A, Dorado P. Source: European Journal of Clinical Pharmacology. 2002 June; 58(3): 223-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12162273
•
QTc prolongation: possible association with risperidone and/or haloperidol. Author(s): Nandagopal JJ, Craig JM, Lippmann S. Source: Psychosomatics. 2003 November-December; 44(6): 521. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597690
•
Quality of life and response of negative symptoms in schizophrenia to haloperidol and the atypical antipsychotic remoxipride. The Canadian Remoxipride Group. Author(s): Awad AG, Lapierre YD, Angus C, Rylander A. Source: Journal of Psychiatry & Neuroscience : Jpn. 1997 July; 22(4): 244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9262046
•
Quantification of neuroreceptors in living human brain. v. endogenous neurotransmitter inhibition of haloperidol binding in psychosis. Author(s): Gjedde A, Wong DF. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2001 August; 21(8): 98294. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487734
•
Quantification of reduced haloperidol and haloperidol by radioimmunoassay. Author(s): Browning JL, Harrington CA, Davis CM. Source: J Immunoassay. 1985; 6(1-2): 45-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4019788
Studies
85
•
Quantification of the antipsychotics flupentixol and haloperidol in human serum by high-performance liquid chromatography with ultraviolet detection. Author(s): Walter S, Bauer S, Roots I, Brockmoller J. Source: J Chromatogr B Biomed Sci Appl. 1998 December 11; 720(1-2): 231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9892087
•
Quantitative analysis of two pyridinium metabolites of haloperidol in patients with schizophrenia. Author(s): Eyles DW, McLennan HR, Jones A, McGrath JJ, Stedman TJ, Pond SM. Source: Clinical Pharmacology and Therapeutics. 1994 November; 56(5): 512-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7955815
•
Quantitative determination of haloperidol in human plasma by high-performance liquid chromatography. Author(s): Kogan MJ, Pierson D, Verebey K. Source: Therapeutic Drug Monitoring. 1983; 5(4): 485-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6659018
•
Quetiapine is not associated with increase in prolactin secretion in contrast to haloperidol. Author(s): Atmaca M, Kuloglu M, Tezcan E, Canatan H, Gecici O. Source: Archives of Medical Research. 2002 November-December; 33(6): 562-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505103
•
Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Author(s): Galetin A, Clarke SE, Houston JB. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 December; 30(12): 1512-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433827
•
Rapid onset of therapeutic effect of risperidone versus haloperidol in a double-blind randomized trial. Author(s): Rabinowitz J, Hornik T, Davidson M. Source: The Journal of Clinical Psychiatry. 2001 May; 62(5): 343-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11411815
•
Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. Author(s): TREC Collaborative Group. Source: Bmj (Clinical Research Ed.). 2003 September 27; 327(7417): 708-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512476
86
Haloperidol
•
Re: Chan et al. A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients. Int J Geriatr Psychiatry 16: 1156 - 1162. Author(s): Onalaja D, Jainer AK. Source: International Journal of Geriatric Psychiatry. 2002 November; 17(11): 1076-7; Author Reply 1077. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12404659
•
Re: Clomipramine vs. Haloperidol in the treatment of autistic disorder: a doubleblind, placebo, crossover study. Author(s): King R, Fay G, Wheildon H. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 525-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352279
•
Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study. Author(s): Schutz G, Berk M. Source: International Clinical Psychopharmacology. 2001 September; 16(5): 275-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11552770
•
Relationship between haloperidol plasma concentration, debrisoquine metabolic ratio, CYP2D6 and CYP2C9 genotypes in psychiatric patients. Author(s): LLerena A, de la Rubia A, Berecz R, Dorado P. Source: Pharmacopsychiatry. 2004 March; 37(2): 69-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15048614
•
Risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine. Author(s): Schillevoort I, de Boer A, Herings RM, Roos RA, Jansen PA, Leufkens HG. Source: The Annals of Pharmacotherapy. 2001 December; 35(12): 1517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793611
•
Risperidone versus haloperidol in the treatment of acute exacerbations of chronic inpatients with schizophrenia: a randomized double-blind study. Author(s): Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Source: International Clinical Psychopharmacology. 2001 November; 16(6): 325-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712620
•
Ritanserin as an adjunct to lithium and haloperidol for the treatment of medicationnaive patients with acute mania: a double blind and placebo controlled trial. Author(s): Akhondzadeh S, Mohajari H, Reza Mohammadi M, Amini H. Source: Bmc Psychiatry [electronic Resource]. 2003 June 19; 3(1): 7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816549
Studies
87
•
Savoxepine versus haloperidol. Reasons for a failed controlled clinical trial in patients with an acute episode of schizophrenia. Author(s): Volz HP, Moller HJ, Gerebtzoff A, Bischoff S. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 April; 252(2): 76-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111340
•
Sawtooth waves during REM sleep after administration of haloperidol combined with total sleep deprivation in healthy young subjects. Author(s): Pinto LR Jr, Peres CA, Russo RH, Remesar-Lopez AJ, Tufik S. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2002 May; 35(5): 599-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011946
•
Sex differences in clinical response to olanzapine compared with haloperidol. Author(s): Goldstein JM, Cohen LS, Horton NJ, Lee H, Andersen S, Tohen M, Crawford A, Tollefson G. Source: Psychiatry Research. 2002 May 15; 110(1): 27-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12007591
•
Shifting from haloperidol to risperidone for behavioral disturbances in dementia: safety, response predictors, and mood effects. Author(s): Lane HY, Chang YC, Su MH, Chiu CC, Huang MC, Chang WH. Source: Journal of Clinical Psychopharmacology. 2002 February; 22(1): 4-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799336
•
Significant dose effect of carbamazepine on reduction of steady-state plasma concentration of haloperidol in schizophrenic patients. Author(s): Yasui-Furukori N, Kondo T, Mihara K, Suzuki A, Inoue Y, Kaneko S. Source: Journal of Clinical Psychopharmacology. 2003 October; 23(5): 435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520118
•
Single-dose haloperidol for the prophylaxis of postoperative nausea and vomiting after intrathecal morphine. Author(s): Parlow JL, Costache I, Avery N, Turner K. Source: Anesthesia and Analgesia. 2004 April; 98(4): 1072-6, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041601
88
Haloperidol
•
Six-month open trial of haloperidol as an adjunctive treatment for anorexia nervosa: a preliminary report. Author(s): Cassano GB, Miniati M, Pini S, Rotondo A, Banti S, Borri C, Camilleri V, Mauri M. Source: The International Journal of Eating Disorders. 2003 March; 33(2): 172-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616583
•
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
•
Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. Author(s): de Haan L, van Bruggen M, Lavalaye J, Booij J, Dingemans PM, Linszen D. Source: The American Journal of Psychiatry. 2003 February; 160(2): 303-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562577
•
Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study). Author(s): Garcia-Cabeza I, Gomez JC, Sacristan JA, Edgell E, Gonzalez de Chavez M. Source: Bmc Psychiatry [electronic Resource]. 2001; 1(1): 7. Epub 2001 December 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11835695
•
The acute EPS of haloperidol may be unrelated to its metabolic transformation to BCPP+. Author(s): Sikazwe DM, Li S, Lyles-Eggleston M, Ablordeppey SY. Source: Bioorganic & Medicinal Chemistry Letters. 2003 November 3; 13(21): 3779-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552778
•
The effects of clozapine versus haloperidol on measures of impulsive aggression and suicidality in chronic schizophrenia patients: an open, nonrandomized, 6-month study. Author(s): Spivak B, Shabash E, Sheitman B, Weizman A, Mester R. Source: The Journal of Clinical Psychiatry. 2003 July; 64(7): 755-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12934974
Studies
89
•
The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy. Author(s): Schulz SC, Thomson R, Brecher M. Source: Schizophrenia Research. 2003 July 1; 62(1-2): 1-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765737
•
The impact of olanzapine, risperidone, or haloperidol on the cost of schizophrenia care in a medicaid population. Author(s): Gibson PJ, Damler R, Jackson EA, Wilder T, Ramsey JL. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2004 January-February; 7(1): 22-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720128
•
The influence of dyslipidemia on the plasma protein and lipoprotein distribution of haloperidol. Author(s): Procyshyn RM, Tsai G, Wasan KM. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 January; 13(1): 33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480120
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The relationship of clozapine and haloperidol treatment response to prefrontal, hippocampal, and caudate brain volumes. Author(s): Arango C, Breier A, McMahon R, Carpenter WT Jr, Buchanan RW. Source: The American Journal of Psychiatry. 2003 August; 160(8): 1421-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900303
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The tolerability of intramuscular ziprasidone and haloperidol treatment and the transition to oral therapy. Author(s): Daniel DG, Zimbroff DL, Swift RH, Harrigan EP. Source: International Clinical Psychopharmacology. 2004 January; 19(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101564
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Torsade de pointes associated with the administration of intravenous haloperidol. Author(s): Hassaballa HA, Balk RA. Source: American Journal of Therapeutics. 2003 January-February; 10(1): 58-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522522
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Torsade de pointes associated with the administration of intravenous haloperidol:a review of the literature and practical guidelines for use. Author(s): Hassaballa HA, Balk RA. Source: Expert Opinion on Drug Safety. 2003 November; 2(6): 543-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585064
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Transdermal drug delivery system of haloperidol to overcome self-induced extrapyramidal syndrome. Author(s): Samanta MK, Dube R, Suresh B. Source: Drug Development and Industrial Pharmacy. 2003 April; 29(4): 405-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737534
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Urinary retention in the course of neuroleptic therapy with haloperidol. Author(s): Ulmar G, Schunck H, Kober C. Source: Pharmacopsychiatry. 1988 July; 21(4): 208-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3205888
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Urinary retention with sertraline, haloperidol, and clonazepam combination. Author(s): Benazzi F. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1998 December; 43(10): 1051-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9868574
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Urinary retention with venlafaxine-haloperidol combination. Author(s): Benazzi F. Source: Pharmacopsychiatry. 1997 January; 30(1): 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9065967
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Use of adjunctive novel antipsychotics with depot haloperidol. Author(s): Sattar SP, Fernandes P, Bhatia SC. Source: Psychiatric Services (Washington, D.C.). 2003 July; 54(7): 1040-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851447
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Use of antisera in the isolation of human specific conjugates of haloperidol. Author(s): Oida T, Terauchi Y, Yoshida K, Kagemoto A, Sekine Y. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1989 July; 19(7): 781-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2773512
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Use of haloperidol infusions to control delirium in critically ill adults. Author(s): Seneff MG, Mathews RA. Source: The Annals of Pharmacotherapy. 1995 July-August; 29(7-8): 690-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8520081
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Use of haloperidol preoperatively. Author(s): Barasch KR. Source: Journal of Cataract and Refractive Surgery. 1988 May; 14(3): 349. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3397899
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Use of high-dose intravenous haloperidol in the treatment of agitated cardiac patients. Author(s): Tesar GE, Murray GB, Cassem NH. Source: Journal of Clinical Psychopharmacology. 1985 December; 5(6): 344-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4067002
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Usefulness of plasma haloperidol levels for monitoring clinical efficacy and side effects in Alzheimer patients with psychosis and behavioral dyscontrol. Author(s): Pelton GH, Devanand DP, Bell K, Marder K, Marston K, Liu X, Cooper TB. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2003 March-April; 11(2): 186-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611748
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Using ofloxacin as a time marker in hair analysis for monitoring the dosage history of haloperidol. Author(s): Nakano M, Uematsu T, Sato H, Kosuge K, Nishimoto M, Nakashima M. Source: European Journal of Clinical Pharmacology. 1994; 47(2): 195-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7859809
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Ventricular ectopy associated with low-dose intravenous haloperidol and electroconvulsive therapy. Author(s): Greene YM, McDonald WM, Duggan J, Cooper R. Source: The Journal of Ect. 2000 September; 16(3): 309-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11005056
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Visual compatibility of haloperidol lactate with 0.9% sodium chloride injection or injectable critical-care drugs during simulated Y-site injection. Author(s): Outman WR, Monolakis J. Source: Am J Hosp Pharm. 1991 July; 48(7): 1539-41. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1882889
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Visual compatibility of haloperidol lactate with injectable solutions. Author(s): Fraser GL, Riker RR. Source: Am J Hosp Pharm. 1994 April 1; 51(7): 905-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8017441
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Water handling in patients receiving haloperidol decanoate. Author(s): Rider JM, Mauger TF, Jameson JP, Notman DD. Source: The Annals of Pharmacotherapy. 1995 July-August; 29(7-8): 663-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8520076
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Weight gain and prolactin levels in patients on long-term antipsychotic medication: a double-blind comparative trial of haloperidol decanoate and fluphenazine decanoate. Author(s): Cookson JC, Kennedy NM, Gribbon D. Source: International Clinical Psychopharmacology. 1986 July; 1 Suppl 1: 41-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3549879
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Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study. Author(s): Bobes J, Rejas J, Garcia-Garcia M, Rico-Villademoros F, Garcia-Portilla MP, Fernandez I, Hernandez G; EIRE Study Group. Source: Schizophrenia Research. 2003 July 1; 62(1-2): 77-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765747
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Weight gain, serum leptin and triglyceride levels in patients with schizophrenia on antipsychotic treatment with quetiapine, olanzapine and haloperidol. Author(s): Atmaca M, Kuloglu M, Tezcan E, Gecici O, Ustundag B. Source: Schizophrenia Research. 2003 March 1; 60(1): 99-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505146
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Wheat gluten and haloperidol. Author(s): Luchins DJ, Freed WJ, Potkin S, Rosenblatt JE, Gillin JC, Wyatt RJ. Source: Biological Psychiatry. 1980 October; 15(5): 819-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7417635
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Withdrawal emergent syndrome in an infant associated with maternal haloperidol therapy. Author(s): Sexson WR, Barak Y. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 1989 June; 9(2): 170-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2738729
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Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study. Author(s): Cohen-Mansfield J, Lipson S, Werner P, Billig N, Taylor L, Woosley R. Source: Archives of Internal Medicine. 1999 August 9-23; 159(15): 1733-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448776
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Zotepine in the treatment of schizophrenic patients with prevailingly negative symptoms. A double-blind trial vs. haloperidol. Author(s): Barnas C, Stuppack CH, Miller C, Haring C, Sperner-Unterweger B, Fleischhacker WW. Source: International Clinical Psychopharmacology. 1992 Spring; 7(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1352521
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Zotepine vs. haloperidol in paranoid schizophrenia: a double-blind trial. Author(s): Fleischhacker WW, Barnas C, Stuppack CH, Unterweger B, Miller C, Hinterhuber H. Source: Psychopharmacology Bulletin. 1989; 25(1): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2570438
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Zuclopenthixol and haloperidol in patients with acute psychotic states. A doubleblind, multi-centre study. Author(s): Heikkila L, Eliander H, Vartiainen H, Turunen M, Pedersen V. Source: Current Medical Research and Opinion. 1992; 12(9): 594-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1582239
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Zuclopenthixol and haloperidol/levomepromazine in the treatment of elderly patients with symptoms of aggressiveness and agitation: a double-blind, multi-centre study. Author(s): Fuglum E, Schillinger A, Andersen JB, Belstad BE, Jensen D, Muller F, Muller KJ, Schulstad B, Elgen K. Source: Pharmatherapeutica. 1989; 5(5): 285-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2568639
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Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study. Author(s): Wistedt B, Koskinen T, Thelander S, Nerdrum T, Pedersen V, Molbjerg C. Source: Acta Psychiatrica Scandinavica. 1991 July; 84(1): 14-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1681680
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Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia. Author(s): Lublin H, Gerlach J, Hagert U, Meidahl B, Molbjerg C, Pedersen V, Rendtorff C, Tolvanen E. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1991 December; 1(4): 541-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1822319
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Zuclopenthixol, melperone and haloperidol/levomepromazine in the elderly. Metaanalysis of two double-blind trials at 15 nursing homes in Norway. Author(s): Nygaard HA, Fuglum E, Elgen K. Source: Current Medical Research and Opinion. 1992; 12(10): 615-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1353014
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CHAPTER 2. NUTRITION AND HALOPERIDOL Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and haloperidol.
Finding Nutrition Studies on Haloperidol 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 “haloperidol” (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 information is typical of that found when using the “Full IBIDS Database” to search for “haloperidol” (or a synonym): •
A comparison of olanzapine with haloperidol in cannabis-induced psychotic disorder: a double-blind randomized controlled trial. Author(s): Department of Psychiatry, University of the Witwatersrand Medical School, Parktown, South Africa.
[email protected] Source: Berk, M Brook, S Trandafir, A I Int-Clin-Psychopharmacol. 1999 May; 14(3): 17780 0268-1315
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Chronic ascorbate potentiates the effects of chronic haloperidol on behavioral supersensitivity but not D2 dopamine receptor binding. Author(s): Department of Psychology, Indiana University, Bloomington 47405. Source: Pierce, R C Rowlett, J K Bardo, M T Rebec, G V Neuroscience. 1991; 45(2): 373-8 0306-4522
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Combined treatment of schizophrenic psychoses with haloperidol and valproate. Author(s): Psychiatric District Hospital, Taufkirchen, Germany. Source: Dose, M Hellweg, R Yassouridis, A Theison, M Emrich, H Pharmacopsychiatry. 1998 July; 31(4): 122-5 0176-3679
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Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man. Author(s): Department of Psychiatry, University of Nottingham, Queen's Medical Centre, UK. Source: Abduljawad, K A Langley, R W Bradshaw, C M Szabadi, E J-Psychopharmacol. 1998; 12(3): 239-45 0269-8811
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Effects of chronic haloperidol and clozapine on vacuous chewing and dopaminemediated jaw movements in rats: evaluation of a revised animal model of tardive dyskinesia. Author(s): Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan. Source: Ikeda, H Adachi, K Hasegawa, M Sato, M Hirose, N Koshikawa, N Cools, A R JNeural-Transm. 1999; 106(11-12): 1205-16
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Effects of lithium and haloperidol on human sperm motility in-vitro. Author(s): Department of Neurology, Kaohsiung Medical College, Taiwan, Republic of China. Source: Shen, M R Yang, R C Chen, S S J-Pharm-Pharmacol. 1992 June; 44(6): 534-6 00223573
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Intra-striatal haloperidol and scopolamine injections: effects on choice reaction time performance in rats. Author(s): Faculty of Psychology, Section of Biological Psychology, Maastricht, The Netherlands.
[email protected] Source: Blokland, A Honig, W Eur-Neuropsychopharmacol. 1999 December; 9(6): 523-31 0924-977X
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Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation. Author(s): Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd, Japan. Source: Kudo, S Odomi, M Eur-J-Clin-Pharmacol. 1998 May; 54(3): 253-9 0031-6970
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Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice. Author(s): Department of Neuropsychiatry, Hirosaki University School of Medicine, Japan.
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Source: Yasui, N Kondo, T Suzuki, A Otani, K Mihara, K Furukori, H Kaneko, S Inoue, Y Int-Clin-Psychopharmacol. 1999 March; 14(2): 113-8 0268-1315 •
Lithium and haloperidol differentially alter the dynorphin A (1-8) and enkephalin levels in the neurointermediate lobe of rat pituitary. Author(s): Department of Pharmacology and Toxicology, Northwest Center for Medical Education, Indiana University School of Medicine, Gary 46408. Source: Sivam, S P Smith, D R Takeuchi, K Hong, J S Neuropeptides. 1987 October; 10(3): 291-8 0143-4179
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Oral Dyskinesias and striatal lesions in rats after long-term co-treatment with haloperidol and 3-nitropropionic acid. Author(s): Department of Physiology, Sandviken Hospital, University of Bergen, Norway. Source: Andreassen, O A Ferrante, R J Beal, M F Jorgensen, H A Neuroscience. 1998 December; 87(3): 639-48 0306-4522
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Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics. Author(s): Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Hosur Road, Bangalore 560 029, India. Source: Balijepalli, S Kenchappa, R S Boyd, M R Ravindranath, V Neurochem-Int. 2001 April; 38(5): 425-35 0197-0186
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Terpenes in ethanol: haloperidol permeation and partition through human skin and stratum corneum changes. Author(s): Department of Pharmacy, Faculty of Science, 18, Science Drive 4, National University of Singapore, 117543, Singapore, Singapore. Source: Vaddi, H K Ho, P C Chan, Y W Chan, S Y J-Control-Release. 2002 May 17; 81(12): 121-33 0168-3659
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 haloperidol; 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 E Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Iron Source: Healthnotes, Inc.; www.healthnotes.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND HALOPERIDOL Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to haloperidol. 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 haloperidol 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 “haloperidol” (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 haloperidol: •
A comparison of olanzapine with haloperidol in cannabis-induced psychotic disorder: a double-blind randomized controlled trial. Author(s): Berk M, Brook S, Trandafir AI. Source: International Clinical Psychopharmacology. 1999 May; 14(3): 177-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435771
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A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia. Author(s): Zhang XY, Zhou DF, Zhang PY, Wu GY, Su JM, Cao LY. Source: The Journal of Clinical Psychiatry. 2001 November; 62(11): 878-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11775047
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Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: implications for a possible antipsychotic action of
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ondansetron. Author(s): Warburton EC, Joseph MH, Feldon J, Weiner I, Gray JA. Source: Psychopharmacology. 1994 May; 114(4): 657-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7855229 •
Antipsychotic drug effects in a model of schizophrenic attentional disorder: a randomized controlled trial of the effects of haloperidol on latent inhibition in healthy people. Author(s): Williams JH, Wellman NA, Geaney DP, Cowen PJ, Feldon J, Rawlins JN. Source: Biological Psychiatry. 1996 December 1; 40(11): 1135-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8931917
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Behavior modification and haloperidol in chronic facial pain. Author(s): Raft D, Toomey T, Gregg JM. Source: Southern Medical Journal. 1979 February; 72(2): 155-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=371002
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Case study of circadian rhythm sleep disorder following haloperidol treatment: reversal by risperidone and melatonin. Author(s): Ayalon L, Hermesh H, Dagan Y. Source: Chronobiology International. 2002 September; 19(5): 947-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12405556
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Circadian rhythm of brain susceptibility to haloperidol during chronic administration. Author(s): Nagayama H, Takagi A, Yoshimoto S, Minami H, Nishiwaki K, Takahashi R. Source: Pharmacology, Biochemistry, and Behavior. 1982 February; 16(2): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7200239
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Clinical and pharmacological effects of monoamine precursors or haloperidol in chronic schizophrenia. Author(s): Persson T, Roos BE. Source: Nature. 1968 March 2; 217(131): 854. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5300360
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Clozapine but not haloperidol Re-establishes normal task-activated rCBF patterns in schizophrenia within the anterior cingulate cortex. Author(s): Lahti AC, Holcomb HH, Weiler MA, Medoff DR, Frey KN, Hardin M, Tamminga CA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 January; 29(1): 171-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520337
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Deficient sensorimotor gating after 6-hydroxydopamine lesion of the rat medial prefrontal cortex is reversed by haloperidol. Author(s): Koch M, Bubser M. Source: The European Journal of Neuroscience. 1994 December 1; 6(12): 1837-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7704295
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Disruption of prepulse inhibition following N-methyl-D-aspartate infusion into the ventral hippocampus is antagonized by clozapine but not by haloperidol: a possible model for the screening of atypical antipsychotics. Author(s): Zhang W, Pouzet B, Jongen-Relo AL, Weiner I, Feldon J. Source: Neuroreport. 1999 August 20; 10(12): 2533-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574365
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Effect of diazepam, apomorphine and haloperidol on the audiogenic immobility reaction and on the open field behavior. Author(s): Hard E, Engel J, Larsson K, Musi B. Source: Psychopharmacology. 1985; 85(1): 106-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3920692
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Effect of d-limonene, alpha-pinene and cineole on in vitro transdermal human skin penetration of chlorpromazine and haloperidol. Author(s): Almirall M, Montana J, Escribano E, Obach R, Berrozpe JD. Source: Arzneimittel-Forschung. 1996 July; 46(7): 676-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8842336
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Effect of haloperidol and pimozide on acetylcholine output from the cerebral cortex in rats and guinea pigs. Author(s): Casamenti F, Bianchi C, Beani L, Pepeu G. Source: European Journal of Pharmacology. 1980 July 25; 65(2-3): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7398789
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Effect of melperone, chlorpromazine, haloperidol, and diazepam on experimental anxiety in normal subjects. Author(s): Molander L. Source: Psychopharmacology. 1982; 77(2): 109-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6126901
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Effect of undernutrition on morphine analgesia, haloperidol catalepsy and pentobarbitone sodium hypnosis in developing new born rats. Author(s): Singh KP, Sanyal AK. Source: Indian Journal of Medical Sciences. 2003 April; 57(4): 164-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510349
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Effect of Withania somnifera root extract on haloperidol-induced orofacial dyskinesia: possible mechanisms of action. Author(s): Naidu PS, Singh A, Kulkarni SK. Source: Journal of Medicinal Food. 2003 Summer; 6(2): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935321
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Effects of apomorphine and haloperidol on the acoustic startle response in rats. Author(s): Davis M, Aghajanian GK. Source: Psychopharmacology. 1976 June 23; 47(3): 217-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=823557
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Effects of bromocriptine and haloperidol on ethanol withdrawal syndrome in rats. Author(s): Uzbay IT, Akarsu ES, Kayaalp SO. Source: Pharmacology, Biochemistry, and Behavior. 1994 December; 49(4): 969-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7886115
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Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man. Author(s): Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 1998; 12(3): 239-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10958249
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Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man. Author(s): Martin-Iverson MT. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(2): 198-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10475729
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Effects of bromocriptine and haloperidol on prepulse inhibition: comparison of the acoustic startle eyeblink response and the N1/P2 auditory-evoked response in man. Author(s): Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(1): 3-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10221354
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Effects of chronic olanzapine and haloperidol differ on the mouse N1 auditory evoked potential. Author(s): Maxwell CR, Liang Y, Weightman BD, Kanes SJ, Abel T, Gur RE, Turetsky BI, Bilker WB, Lenox RH, Siegel SJ. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 April; 29(4): 739-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735128
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Effects of haloperidol and chlorpromazine on central adrenergic and cholinergic mechanisms in rabbits. Author(s): Consroe PF, White RP. Source: Arch Int Pharmacodyn Ther. 1972; 198(1): 67-75. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5053242
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Effects of haloperidol and clozapine on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man. Author(s): Graham SJ, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 24350. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11769817
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Effects of haloperidol and SCH 23390 on acoustic startle and prepulse inhibition under basal and stimulated conditions. Author(s): Schwarzkopf SB, Bruno JP, Mitra T. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1993 November; 17(6): 1023-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8278596
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Effects of haloperidol on selective attention: a combined whole-head MEG and highresolution EEG study. Author(s): Kahkonen S, Ahveninen J, Jaaskelainen IP, Kaakkola S, Naatanen R, Huttunen J, Pekkonen E. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 October; 25(4): 498-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557163
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Effects of ketanserin and haloperidol on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man. Author(s): Graham SJ, Langley RW, Balboa VA, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 2002 March; 16(1): 15-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11949767
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Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin. Author(s): Liechti ME, Geyer MA, Hell D, Vollenweider FX. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 March; 24(3): 240-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11166515
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Effects of single oral administrations of haloperidol and d-amphetamine on prepulse inhibition of the acoustic startle reflex in healthy male volunteers.
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Author(s): Kumari V, Mulligan OF, Cotter PA, Poon L, Toone BK, Checkley SA, Gray JA. Source: Behavioural Pharmacology. 1998 November; 9(7): 567-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862082 •
Extract of Ginkgo biloba added to haloperidol was effective for positive symptoms in refractory schizophrenia. Author(s): Knable MB. Source: Evidence-Based Mental Health. 2002 August; 5(3): 90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180457
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Facilitation of latent inhibition by haloperidol in rats. Author(s): Weiner I, Feldon J. Source: Psychopharmacology. 1987; 91(2): 248-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3107041
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First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol. Author(s): Green AI, Tohen MF, Hamer RM, Strakowski SM, Lieberman JA, Glick I, Clark WS; HGDH Research Group. Source: Schizophrenia Research. 2004 February 1; 66(2-3): 125-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061244
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Genetics, haloperidol-induced catalepsy and haloperidol-induced changes in acoustic startle and prepulse inhibition. Author(s): McCaughran J Jr, Mahjubi E, Decena E, Hitzemann R. Source: Psychopharmacology. 1997 November; 134(2): 131-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399376
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Gilles de la Tourette's syndrome--an overview of development and treatment of a case, using hypnotherapy, haloperidol, and psychotherapy. Author(s): Clements RO. Source: Am J Clin Hypn. 1972 January; 14(3): 167-72. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4526606
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Haloperidol affects stimulus-dependent strategies and not reward-dependent strategies. Author(s): Coenders CJ, Kerbusch SM, Vossen JM. Source: Brain Research Bulletin. 1993; 32(1): 7-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8319106
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Haloperidol- and apomorphine-induced changes in pup searching behaviour of house mice. Author(s): Wegener S, Schmidt WJ, Ehret G. Source: Psychopharmacology. 1988; 95(2): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3137610
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Haloperidol- and clozapine-induced enhancement of latent inhibition with extended conditioning: implications for the mechanism of action of neuroleptic drugs. Author(s): Weiner I, Shadach E, Barkai R, Feldon J. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1997 January; 16(1): 42-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8981387
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Haloperidol challenge in healthy male humans: a functional magnetic resonance imaging study. Author(s): Brassen S, Tost H, Hoehn F, Weber-Fahr W, Klein S, Braus DF. Source: Neuroscience Letters. 2003 April 17; 340(3): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672539
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Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick. Author(s): Gruss M, Bock J, Braun K. Source: Journal of Neurochemistry. 2003 November; 87(3): 686-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535951
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Inhibition of haloperidol-induced catalepsy in rats by root extracts from Piper methysticum F. Author(s): Noldner M, Chatterjee SS. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 1999 October; 6(4): 285-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10589449
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Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice. Author(s): Yasui N, Kondo T, Suzuki A, Otani K, Mihara K, Furukori H, Kaneko S, Inoue Y. Source: International Clinical Psychopharmacology. 1999 March; 14(2): 113-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10220126
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Modulation of language processing in schizophrenia: effects of context and haloperidol on the event-related potential. Author(s): Condray R, Steinhauer SR, Cohen JD, van Kammen DP, Kasparek A.
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Source: Biological Psychiatry. 1999 May 15; 45(10): 1336-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10349041 •
Morphine versus haloperidol catalepsy in the rat: a behavioral analysis of postural support mechanisms. Author(s): De Ryck M, Schallert T, Teitelbaum P. Source: Brain Research. 1980 November 10; 201(1): 143-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7191346
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Neurochemical and motor effects of high dose haloperidol treatment: exacerbation by tryptophan supplementation. Author(s): Johnson SK, Wagner GC, Fischer H. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1992 September; 200(4): 571-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1380718
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Oral dyskinesias and histopathological alterations in substantia nigra after long-term haloperidol treatment of old rats. Author(s): Andreassen OA, Ferrante RJ, Aamo TO, Beal MF, Jorgensen HA. Source: Neuroscience. 2003; 122(3): 717-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622915
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Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol. Author(s): Duncan E, Szilagyi S, Schwartz M, Kunzova A, Negi S, Efferen T, Peselow E, Chakravorty S, Stephanides M, Harmon J, Bugarski-Kirola D, Gonzenbach S, Rotrosen J. Source: Psychiatry Research. 2003 August 30; 120(1): 1-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500109
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Quercetin, a bioflavonoid, attenuates haloperidol-induced orofacial dyskinesia. Author(s): Naidu PS, Singh A, Kulkarni SK. Source: Neuropharmacology. 2003 June; 44(8): 1100-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763102
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Reversal of haloperidol-induced orofacial dyskinesia by quercetin, a bioflavonoid. Author(s): Naidu PS, Singh A, Kulkarni SK. Source: Psychopharmacology. 2003 June; 167(4): 418-23. Epub 2003 April 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12669184
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Reversal of vinblastine resistance in human leukemic cells by haloperidol and dihydrohaloperidol. Author(s): Kataoka Y, Ishikawa M, Miura M, Takeshita M, Fujita R, Furusawa S, Takayanagi M, Takayanagi Y, Sasaki K.
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Source: Biological & Pharmaceutical Bulletin. 2001 June; 24(6): 612-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11411546 •
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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The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers. Author(s): McCartan D, Bell R, Green JF, Campbell C, Trimble K, Pickering A, King DJ. Source: Journal of Psychopharmacology (Oxford, England). 2001 June; 15(2): 96-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448094
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The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia. Author(s): Zhang XY, Zhou DF, Su JM, Zhang PY. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 85-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11199954
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The effects of classic antipsychotic haloperidol plus the extract of ginkgo biloba on superoxide dismutase in patients with chronic refractory schizophrenia. Author(s): Zhou D, Zhang X, Su J, Nan Z, Cui Y, Liu J, Guan Z, Zhang P, Shen Y. Source: Chinese Medical Journal. 1999 December; 112(12): 1093-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721446
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The effects of haloperidol and clozapine on the disruption of sensorimotor gating induced by the noncompetitive glutamate antagonist MK-801. Author(s): Hoffman DC, Donovan H, Cassella JV. Source: Psychopharmacology. 1993; 111(3): 339-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7870972
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The haloperidol effect on the histofluorescence in the caudate nucleus of the rat brain treated with agonistic and antagonistic acetylcholine compounds. Author(s): Wawrzyniak M, Cybulska R. Source: Folia Histochem Cytochem (Krakow). 1981; 19(3): 143-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7327444
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The latent inhibition model dissociates between clozapine, haloperidol, and ritanserin. Author(s): Shadach E, Gaisler I, Schiller D, Weiner I.
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Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2000 August; 23(2): 151-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10882841
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 haloperidol; 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 Morning Sickness Source: Healthnotes, Inc.; www.healthnotes.com Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements General Anesthetics Source: Healthnotes, Inc.; www.healthnotes.com Glycine Source: Healthnotes, Inc.; www.healthnotes.com Haloperidol Source: Healthnotes, Inc.; www.healthnotes.com Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zingiber Alternative names: Ginger; Zingiber officinale Roscoe 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 HALOPERIDOL Overview In this chapter, we will give you a bibliography on recent dissertations relating to haloperidol. 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 “haloperidol” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on haloperidol, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Haloperidol 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 haloperidol. 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: •
Contrasting the effects of haloperidol and olanzapine on attention and working memory in schizophrenia: A double-blind flexible dose study by Boulay, Luc Jean, PhD from CARLETON UNIVERSITY (CANADA), 2003, 301 pages http://wwwlib.umi.com/dissertations/fullcit/NQ83513
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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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The effects of nigrostriatal microinjections of haloperidol on forelimb movement initiation and phasing (basal ganglia, reactive capacity) by Alford, Elward Kendall, PhD from THE UNIVERSITY OF TEXAS AT AUSTIN, 1985, 169 pages http://wwwlib.umi.com/dissertations/fullcit/8527679
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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 HALOPERIDOL 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 “haloperidol” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on haloperidol, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Haloperidol By performing a patent search focusing on haloperidol, 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 haloperidol: •
Acetic acid ester of haloperidol Inventor(s): Perregaard; Jens K. (Olstykke, DK) Assignee(s): H. Lundbeck A/S (Copenhagen, DK) Patent Number: 4,855,307 Date filed: September 4, 1987 Abstract: The present invention relates to the novel acetic acid ester of 4-(4-(4chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4-fluorophenyl)-1-butano ne, as well as pharmaceutically acceptable acid addition salts thereof, a method of preparation, pharmaceutical compositions and a method of treating psychoses by administering said ester to an animal or human body. Excerpt(s): The compound 4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4fluorophenyl)-1-butano ne, known as haloperidol (INN), has for many years been a widely used neuroleptic in the treatment of severe psychotic conditions including schizophrenic disorders. So far, haloperidol has been administered orally or in form of aqueous solutions for injection containing haloperidol and lactic acid. Moreover, a very long acting depot preparation consisting of the decanoic acid ester of haloperidol in sesame oil is known. The aqueous solution for injection which is relatively short acting and used in the acute phase, has however in most cases very serious side effects at the site of injection in the form of necrosis of the muscle tissue. Web site: http://www.delphion.com/details?pn=US04855307__
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Controlled delivery of haloperidol by an osmotic delivery system Inventor(s): Ayer; Atul (Mountain View, CA), Theeuwes; Felix (Los Altos, CA), Wong; Patrick S. L. (Hayward, CA) Assignee(s): ALZA Corporation (Palo Alto, CA) Patent Number: 4,610,686 Date filed: November 2, 1983 Abstract: An osmotic system is disclosed for the delivery of haloperidol at a controlled rate over a prolonged period of time. Excerpt(s): This invention pertains to the controlled delivery of a therapeutically useful amount of haloperidol by an osmotic delivery system. The invention concerns also both a process for solubilizing haloperidol and an improved method for producing a therapeutic effect by administering the solubilized haloperidol. Haloperidol, also known as 4-[4-(-chlorophenyl)-4-hydroxy-1-piperidnyl]-1-(4-fluorophenyl)-1-butanone , is a tranquilizer drug indicated for the management of manifestation of psychotic disorders. Haloperidol is specifically indicated as an antipsychotic drug useful for the treatment of acute and chronic schizophrenia. Presently, haloperidol is available as conventional tablets. These noncontrolled dosage tablets containing 0.5 mg to 2.0 mg of haloperidol are administered to patients of moderate symptomatology twice or thrice daily, and the same tablet containing 3.0 mg to 5.0 mg of haloperidol are administered to patients of severe symptomatology also twice or thrice daily.
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Web site: http://www.delphion.com/details?pn=US04610686__ •
Method for treating schizophrenia and medicaments therefor Inventor(s): Harrigan; Stephen E. (Ann Arbor, MI), Heffner; Thomas G. (Ann Arbor, MI), Weisbach; Jerry A. (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 4,582,823 Date filed: August 15, 1984 Abstract: A method for treating schizophrenia without precipitating neurological side effects such as extrapyramidal syndrome and tardive dyskinesia by administering prior to or concomitantly with haloperidol a diphenylalkyladenosine or diphenylalkyl-2amino-adenosine is described as well as pharmaceutical compositions therefor. Excerpt(s): Haloperidol, described in U.S. Pat. No. 3,438,991, is a well-known neuroleptic agent used for treating psychoses, such as schizophrenia. Use of haloperidol causes side effects including acute extrapyramidal syndrome (EPS) which is usually seen soon after antipsychotic therapy is begun as well as the more chronic dystonic syndrome known as tardive dyskinesia which sometimes emerges during long-term antipsychotic use. Attempts at reducing the side effects of haloperidol have been reported. U.S. Pat. No. 3,978,216 describes the use of a gabergic compound administered prior to or with a neuroleptic agent to reduce tardive dyskinesia. Benzodiazepines have been reported to be effective in the reduction of serum prolactin when used with haloperidol, U.S. Pat. No. 4,316,897. Desipramine and imipramine have been reported to reduce Parkinsonlike symptoms in the treatment of schizophrenia with haloperidol in U.S. Pat. No.3,505,451. The present invention has for its object a method of treating psychoses, e.g., schizophrenia, and reducing the side effects of such treatment, such as acute extrapyramidal syndrome and tardive dyskinesia by administering a novel adenosine derivative prior to or concomitant with haloperidol therapy. Web site: http://www.delphion.com/details?pn=US04582823__
•
Sustained release microsphere preparation containing antipsychotic drug and production process thereof Inventor(s): Kino; Shigemi (Fukuoka, JP), Mizuta; Hiroaki (Fukuoka, JP), Osajima; Tomonori (Fukuoka, JP) Assignee(s): Yoshitomi Pharmaceutical Industries, Ltd. (Osaka, JP) Patent Number: 5,656,299 Date filed: May 17, 1995 Abstract: A sustained release microsphere preparation which is produced by including a hydrophobic antipsychotic drug such as bromperidol, haloperidol or the like into a base composed of a high molecular weight polymer having in vivo histocompatibility such as polylactic acid, poly(lactic-co-glycolic)acid or the like, and a process for the production thereof. Excerpt(s): This is a continuation-in-part application of PCT/JP93/01673, filed Nov. 15, 1993. This invention relates to a sustained release microsphere preparation which contains a hydrophobic antipsychotic drug and to a process for producing the
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preparation. It is said that, in the drug therapy of mental diseases, maintenance therapy by continuous administration is effective in preventing recidivism of symptoms, whereby it is possible to guide patients in their daily lives. However, since the current maintenance therapy with antipsychotic drugs is carried out by orally administering tablets or fine granules once a day or dividing the daily dose into several doses per day, decreased patient compliance during the maintenance therapy causes recidivism of symptoms or re-hospitalization. Consequently, current maintenance therapy has a drawback in that certain means must be employed to improve compliance after rehabilitation or during outpatient maintenance therapy. Web site: http://www.delphion.com/details?pn=US05656299__ •
Therapeutic combinations of mirtazapine and antipsychotic agents, for the treatment or prophylaxis of psychotic disorders Inventor(s): Berendsen; Hermanus Henricus Gerardus (Geffen, NL), Broekkamp; Christophorus Louis Eduard (Oss, NL), Pinder; Roger Martin (Oss, NL) Assignee(s): Akzo Nobel N.V. (Arnhem, NL) Patent Number: 6,150,353 Date filed: September 7, 1999 Abstract: This application relates to a combination of the antidepressant mirtazapine and an antipsychotic agent such as haloperidol for the treatment of psychotic disorders. Excerpt(s): The present invention relates to therapeutic combinations of mirtazapine and an antipsychotic agent, to pharmaceutical compositions containing said combinations and to their use in the treatment or prophylaxis of psychotic disorders. The term antipsychotic agent includes those classical antipsychotics which work via dopamine D.sub.2 receptor blockade and which are often referred to as "typical" antipsychotics or neuroleptics, and those new antipsychotics which are referred to as "atypical" antipsychotic agents. This atypicality has been defined in a number of ways, but recently it has been defined as the property of providing equal efficacy to established antipsychotic agents while producing fewer extrapyramidal side effects (Meltzer H. Y. Br. J. Psychiatry, 1996, 168 Suppl. 129:23-31). Examples of such typical and atypical antipsychotics include acepromazine, chlorproethazine, chlorpromazine, cyamemazine fluopromazine, methotrimeprazine, promazine, mesoridazine, pericyazine, piperacetazine, pipothiazine, sulforidazine, thioridazine, acetophenazine, carphenazine, dixyrazine, fluphenazine, perazine, perphenazine, prochlorperazine thiopropazate, thioproperazine, trifluperazine, chlorprothixene, flupenthixol, thiothixene, zuclopenthixol, benperidol, bromperidol, droperidol, fluanisone, haloperidol, melperone, moperone, pipamperone, spiperone, timiperone, trifluperidol, fluspirilene, penfluridol, pimozide, amisulpride, raclopride, remoxipride, sulpiride, sultopride, tiapride, molindone, oxypertine, clozapine, loxapine, risperidone, olanzapine, sertindole, quetiapine and ziprasidone. It has now been found that the administration of mirtazapine, which is one of the newest antidepressant agents and has been disclosed in U.S. Pat. No. 4,062,848, in combination with an antipsychotic agent is able to enhance the antipsychotic effect of said antipsychotic. Web site: http://www.delphion.com/details?pn=US06150353__
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Patent Applications on Haloperidol 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 haloperidol: •
Anti-psychosis combination Inventor(s): Behan, Dominic P.; (San Diego, CA), Chalmers, Derek T.; (Cardiff, CA) Correspondence: Woodcock Washburn Llp; One Liberty Place, 46th Floor; 1650 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20020156068 Date filed: March 22, 2002 Abstract: This invention relates to methods of reducing hyperlocomotor activity and stereotypy by administering a composition comprising a modulator of the 5-HT2A receptor with a neuroleptic agent used for treating psychoses, such as Haloperidol. The invention further relates to compositions comprising a modulator of the 5-HT2A receptor with a neuroleptic agent. Excerpt(s): The present application claims priority benefit of Application Serial No. 60/278,516, filed Mar. 22, 2001, the disclosure of which is hereby incorporated by reference in its entirety. The present invention relates to methods of reducing hyperlocomotor activity and stereotypy by co-administering a modulator of the 5-HT2A serotonin receptor having inverse agonist properties at receptor, preferably N-[3-(4bromo-2-methylpyrazol-3-yl)phenyl] [(4-chlorophenyl)amino]carboxamide or a derivative thereof, with a neuroleptic agent used for treating psychoses, such as Haloperidol. The present invention also relates to compositions, including pharmaceutical compositions, comprising a modulator of the 5HT-2A receptor and a neuroleptic. Serotonin, the endogenous ligand for the 5-HT receptor, is thought to play a role in processes related to learning and memory, sleep, thermoregulation, mood, motor activity, pain, sexual and aggressive behaviors, appetite, neurodegenerative regulation, and biological rhythms. Not surprisingly, serotonin is linked to pathophysiological conditions such as anxiety, depression, obsessive-compulsive disorders, schizophrenia, suicide, autism, migraine, emesis, alcoholism, and neurodegenerative disorders. With respect to anti-psychotic treatment approaches focused on the serotonin receptors, these types of therapeutics can generally be divided into two classes, the "typical" and the "a typical." Both have anti-psychotic effects, but the "typicals" also include concomitant motor-related side effects (extra pyramidal syndromes, e.g., lip-smacking, tongue darting, locomotor movement, etc). Such side effects are thought to be associated with the compounds interacting with other receptors, such as the human dopamine D2 receptor in the nigro-striatal pathway. Haloperidol is considered a typical antipsychotic, and Clozapine is considered an a typical anti-psychotic. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
9
This has been a common practice outside the United States prior to December 2000.
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Polymer-based surgically implantable haloperidol delivery systems and methods for their production and use Inventor(s): Gur, Raquel E.; (Philadelphia, PA), Lenox, Robert H.; (Califon, NJ), Siegel, Steven J.; (Berwyn, PA), Winey, Karen I.; (Philadelphia, PA) Correspondence: Licata & Tyrrell P.C.; 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20020179096 Date filed: October 19, 2001 Abstract: Surgically implantable drug delivery systems for long-term delivery of haloperidol containing a biodegradable polymer and haloperidol fabricated into the surgically implantable drug delivery systems via solvent casting and compression molding are provided. Also provided are methods for producing the surgically implantable drug delivery systems and methods for using these systems in the treatment of psychotic disorders such as schizophrenia. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Patent Application Serial No. 60/242,304, filed Oct. 20, 2001. The invention relates to surgically implantable drug delivery systems for the long-term delivery of antipsychotic drugs, and in particular haloperidol. The surgically implantable drug delivery systems of the present invention comprise a biodegradable polymer, preferably a lactide-co-glycolide copolymer, and an antipsychotic drug, preferably haloperidol, fabricated into an implant via solvent casting and compression molding. As demonstrated herein, these formulations, when implanted underneath the skin, release an effective amount of the antipsychotic drug over a period of months. Also provided in the present invention are methods for producing and using these surgically implantable drug delivery systems in the treatment of patients with psychotic disorders such as schizophrenia. While much research regarding the treatment of schizophrenia has focused on new pharmaceutical compounds, a major correctable cause for treatment resistance remains nonadherence with prescribed medication (Fenton et al. Schizophr. Bull. 1997 23(4):637-51; Kane, J. J. Clin. Psychopharmacol. 1985 5(3 Suppl):22s-27s). Approximately 50% of patients with schizophrenia and other chronic psychotic conditions are believed to be poorly adherent with prescribed medication (Young et al. Bull. Am. Acad. Psychiatry Law 1986 14(2):105-22). A controlled study to measure adherence with a detectable marker reported that 80% of patients with schizophrenia do not take medications as prescribed (Kapur et al. Schizophr. Res. 1991 6(1):49-53). Studies of relapsed patients have reported only 30% to meet the criteria for good adherence in the months prior to admission (Bergen et al. Aust. N Z J. Psychiatry 1998 32(6):815-22; Razali et al. Acta Psychiatr. Scand. 1995 91(5):331-5). 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 haloperidol, 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 “haloperidol” (or synonyms) into
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the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on haloperidol. You can also use this procedure to view pending patent applications concerning haloperidol. 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 HALOPERIDOL Overview This chapter provides bibliographic book references relating to haloperidol. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on haloperidol include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Chapters on Haloperidol In order to find chapters that specifically relate to haloperidol, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and haloperidol 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 “haloperidol” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on haloperidol: •
Drugs and the Liver Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.335-363. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: The liver is particularly concerned with drug metabolism, and especially of drugs given orally. Drugs can cause toxic effects that can mimic almost every naturally occurring liver disease in man. This chapter on drugs and the liver is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter is organized into specific pathologies and their potential causes: hepato-cellular zone 3 necrosis, due to carbon tetrachloride, Amanita mushrooms, paracetamol (acetaminophen), salicylates, hyperthermia, hypothermia, and burns;
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hepato-cellular zone 1 necrosis, due to ferrous sulfate or phosphorus; mitochondrial cytopathies, due to sodium valproate, tetracyclines, tacrine, antiviral nucleoside analogues, and Bacillus cereus; steatohepatitis, due to perhexiline maleate, amiodarone, synthetic estrogens, and calcium channel blockers; fibrosis, due to methotrexate, other cytotoxic drugs, arsenic, vinyl chloride, vitamin A, and retinoids; vascular changes, due to sinusoidal dilatation, peliosis hepatitis, and veno-occlusive disease (VOD); acute hepatitis, due to isoniazid, methyl dopa, halothane, hydrofluorocarbons, systemic antifungals, oncology drugs, nervous system modifiers, sustained-release nicotinic acid (niacin), sulfonamides and derivatives, nonsteroidal anti-inflammatory drugs, antithyroid drugs, quinidine and quinine, troglitazone, and anti-convulsants; chronic hepatitis, due to herbal remedies and recreational drugs; canalicular cholestasis, due to cyclosporine A and ciprofloxacin; hepato-canalicular cholestasis, due to chlorpromazine, penicillins, sulfonamides, erythromycin, haloperidol, cimetidine and ranitidine, oral hypoglycemic agents, tamoxifen, other causes, and dextropropoxyphene; ductular cholestasis; biliary sludge; sclerosing cholangitis; hepatic nodules and tumors; and hepatocellular carcinoma (HCC, liver cancer). 28 figures. 5 tables. 170 references.
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CHAPTER 7. PERIODICALS AND NEWS ON HALOPERIDOL Overview In this chapter, we suggest a number of news sources and present various periodicals that cover haloperidol.
News Services and Press Releases One of the simplest ways of tracking press releases on haloperidol 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 “haloperidol” (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 haloperidol. 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 “haloperidol” (or synonyms). The following was recently listed in this archive for haloperidol: •
Risperidone superior to haloperidol in preventing relapse in schizophrenics Source: Reuters Industry Breifing Date: January 03, 2002
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Memory loss due to haloperidol treatment reversible in monkeys Source: Reuters Medical News Date: March 20, 2000
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Risperidone as effective as lithium or haloperidol in treatment of mania Source: Reuters Medical News Date: June 23, 1998
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Pimozide Superior To Haloperidol For Children With Tourette's Disorder Source: Reuters Medical News Date: August 08, 1997
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Olanzapine Superior To Haloperidol For Treatment Of Schizophrenic Psychopathology Source: Reuters Medical News Date: April 07, 1997 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, 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 “haloperidol” (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 “haloperidol” (or synonyms). If you know the name of a company that is relevant to haloperidol, 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/.
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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 “haloperidol” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “haloperidol” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on haloperidol: •
Drugs in the Management of Alzheimer's Victims Source: Alzheimer's Association, San Diego Chapter Newsletter. 6(3): 5. Fall 1988. Contact: Available from Alzheimer's Association, San Diego Chapter. P.O. Box 23877, San Diego, CA 92193. (619) 541-1776. PRICE: Single copies free. Summary: This newsletter article, written by a physician for families of people with Alzheimer's disease, describes the use of drugs in the management of Alzheimer's patients. While no current treatment will stop the degenerative process or produce clinically important improvements in thinking and memory, drug treatment may calm agitation and help relieve some of the confusion caused by Alzheimer's disease. An appropriate drug might be an antipsychotic agent such as haloperidol or phenothiazine. The article emphasizes the importance of trying nondrug treatments first and of tailoring drug choices to the individual.
Academic Periodicals covering Haloperidol Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to haloperidol. In addition to these sources, you can search for articles covering haloperidol 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 haloperidol. 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 haloperidol. 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 haloperidol: Antidyskinetics •
Systemic - U.S. Brands: Akineton; Artane; Artane Sequels; Cogentin; Kemadrin; Parsidol; Trihexane; Trihexy http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202057.html
Droperidol •
Systemic - U.S. Brands: Inapsine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203411.html
Haloperidol •
Systemic - U.S. Brands: Haldol; Haldol Decanoate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202278.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. 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
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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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APPENDICES
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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/
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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
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
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/
•
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
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
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/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
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
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
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
•
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 “haloperidol” (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 17297 54 325 17 86 17779
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 “haloperidol” (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/.
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.
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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 haloperidol 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 haloperidol. 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 haloperidol. 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 “haloperidol”:
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Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Dementia http://www.nlm.nih.gov/medlineplus/dementia.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Schizophrenia http://www.nlm.nih.gov/medlineplus/schizophrenia.html Tourette Syndrome http://www.nlm.nih.gov/medlineplus/tourettesyndrome.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 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 haloperidol. 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
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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•
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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 haloperidol. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with haloperidol. 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 haloperidol. 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 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 “haloperidol” (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 “haloperidol”. 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 “haloperidol” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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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 “haloperidol” (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.21
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
21
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)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
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
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
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
•
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
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
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
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
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
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
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
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
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/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
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
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
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
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
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
•
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
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
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
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
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
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
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/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
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/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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HALOPERIDOL DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Ablation: The removal of an organ by surgery. [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] Acepromazine: A phenothiazine that is used in the treatment of psychoses. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant 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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH]
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Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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] 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] Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
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] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] 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] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] 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
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the injection of procaine. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alcohol Drinking: Behaviors associated with the ingesting of alcoholic beverages, including social drinking. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [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] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU]
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Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [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] Ampulla: A sac-like enlargement of a canal or duct. [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]
Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] 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] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] Angina: Chest pain that originates in the heart. [NIH] 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] Antiallergic: Counteracting allergy or allergic conditions. [EU]
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Antianginal: Counteracting angina or anginal 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] Antidopaminergic: Preventing or counteracting (the effects of) dopamine. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungals: Drugs that treat infections caused by fungi. [NIH] 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] 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] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are 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] Antiproliferative: Counteracting a process of proliferation. [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
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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] Antispasmodic: An agent that relieves spasm. [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] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] 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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] 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] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH]
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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [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] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [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] 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 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] 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] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [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] Autonomic: Self-controlling; functionally independent. [EU] 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] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron
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cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benztropine: A centrally active muscarinic antagonist that has been used in the symptomatic treatment of Parkinson's disease. Benztropine also inhibits the uptake of dopamine. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [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 duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binaural: Used of the two ears functioning together. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific
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combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [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] 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] 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]
Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, 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] 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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It
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uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [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] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [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 functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [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
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for the respiration cycle of plants and animals. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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] 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 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 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 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU]
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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 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] 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] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [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] 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] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Chlorprothixene: A thioxanthine with effects similar to the phenothiazine antipsychotics. [NIH]
Cholangitis: Inflammation of a bile duct. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a
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characteristic feature of atherosclerosis. [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 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] 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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]
Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [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] 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
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cellular arrest in the G2 phase of the cell cycle. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] Clomipramine: A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [NIH]
Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [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] 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] 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] 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
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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 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] 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] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU]
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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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constrict: Tighten; narrow. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [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] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. [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]
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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 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] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [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] Curative: Tending to overcome disease and promote recovery. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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]
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Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [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] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] 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] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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]
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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] 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] Dermatitis: Any inflammation of the skin. [NIH] 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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] 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] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [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] 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
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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] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] 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] 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] 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] 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 Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [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
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poisoning for which specific headings are available. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] 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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH]
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Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancers: 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 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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [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 although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH]
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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] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] 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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] 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] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [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] Flatus: Gas passed through the rectum. [NIH] Flunitrazepam: Benzodiazepine with pharmacologic actions similar to those of diazepam.
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The United States Government has banned the importation of this drug. Steps are being taken to reclassify this substance as a Schedule 1 drug with no accepted medical use. [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] Flupenthixol: This tranquilizer seems to be a dopamine-receptor blocker. It works primarily on the D2 receptors, with some effects on the D1 receptors. Craving in some cocaine addicts becomes manageable but is not eliminated. [NIH] Fluphenazine: A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [NIH] Fluspirilene: A long-acting injectable antipsychotic agent used for chronic schizophrenia. [NIH]
Fossa: A cavity, depression, or pit. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [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] 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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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 Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Geniculate Bodies: Part of the diencephalon inferior to the caudal end of the dorsal
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thalamus. Includes the lateral geniculate body which relays visual impulses from the optic tract to the calcarine cortex, and the medial geniculate body which relays auditory impulses from the lateral lemniscus to the auditory cortex. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Geriatric Psychiatry: A subspecialty of psychiatry concerned with the mental health of the aged. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [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] Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH]
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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]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] 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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Guanfacine: A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [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] 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] 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] Harmaline: Alkaloid isolated from seeds of Peganum harmala L., Zygophyllaceae. A CNS stimulant acting as a monoamine oxidase inhibitor. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria
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in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]
Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [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] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [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] 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 help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Human Activities: Activities performed by humans. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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,
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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 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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] 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] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] 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] Hypnotherapy: Sleeping-cure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] 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] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH]
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Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune function: Production and action of cells that fight disease or infection. [NIH] 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] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] 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] 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] 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] 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] 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
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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] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [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] 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] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [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] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic
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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] 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] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] 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] Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]
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Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [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] 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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] 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]
Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of biogenic monoamines in the central nervous system, and affects multiple neurotransmission systems. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Neoplasms: Tumors or cancer of the liver. [NIH]
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Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] 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] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] 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] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Loxapine: An antipsychotic agent used in schizophrenia. [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] 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] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy 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] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
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Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Mazindol: Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] Membrane: A very thin layer of tissue that covers a surface. [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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] 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 Processes: Conceptual functions or thinking in all its forms. [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]
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] Mesoridazine: A phenothiazine antipsychotic with effects similar to chlorpromazine. [NIH] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [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] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions
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and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [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] MI: 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] Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. [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] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired
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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 Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [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] 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] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Perception: The real or apparent movement of objects through the visual field. [NIH] 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]
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Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidose: Occurring in, or using multiple doses. [EU] Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Nalbuphine: A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu 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] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [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] 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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [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]
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Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
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] 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] 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] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [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] 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] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] 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]
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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] 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] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [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 the individual does not derive pleasure although it may provide a release from tension. [NIH] Oculogyric: Pertaining to, characterized by, or causing oculogyration (circular movements of the eyeballs, as in an oculogyric crisis). [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among
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noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oncology: The study of cancer. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] 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] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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]
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] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by
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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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [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] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Penfluridol: A long-acting antipsychotic used for maintenance or long-term therapy of schizophrenia and other psychoses. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perazine: A phenothiazine antipsychotic with actions and uses similar to those of chlorpromazine. Extrapyramidal symptoms may be more common than other side effects. [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] Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [NIH] 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]
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Perphenazine: An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. [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] 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] 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 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] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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] Phosphorylation: The introduction of a phosphoryl group into a compound through the
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formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] 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]
Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [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] 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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [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] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or
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veins. [EU] Pneumonia: Inflammation of the lungs. [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] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Portal Pressure: The venous pressure measured in the portal vein. [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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Nausea and Vomiting: Emesis and queasiness occurring after anesthesia. [NIH]
Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Postural: Pertaining to posture or position. [EU] 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] 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] 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]
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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] Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]
Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [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] 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] 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] Promazine: A phenothiazine with actions similar to chlorpromazine but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic. [NIH] Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [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
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opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [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] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] 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 Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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 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] 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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [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] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychomotor Agitation: A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. [NIH]
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Psychomotor Performance: The coordination of a sensory or ideational (cognitive) process and a motor activity. [NIH] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]
Psychophysiology: The study of the physiological basis of human and animal behavior. [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] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] 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 hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulvinar: Large mass of nuclei forming the most caudal portion of the thalamus and overhanging the geniculate bodies and the dorsolateral surface of the midbrain. It is divided into four parts: the lateral, medial, inferior, and oral pulvinar nuclei. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and
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uracil) and form the basic structure of the barbiturates. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [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] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and
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interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [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] 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, 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [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] 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] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and
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relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] 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] 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] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [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] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [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] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Ritanserin: A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the
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subjective quality of sleep and decreases portal pressure. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Rolipram: A phosphodiesterase inhibitor with antidepressant properties. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saline: A solution of salt and water. [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] 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] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [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] 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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [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] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH]
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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] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [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]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as 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] 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] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Sludge: A clump of agglutinated red blood cells. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels.
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[NIH]
Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] 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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] 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] 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] Sperm Motility: Ability of the spermatozoon to move by flagellate swimming. [NIH] Spermatozoon: The mature male germ cell. [NIH] 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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Steady state: Dynamic equilibrium. [EU] Stereotypy: Unvarying repetition or unvarying persistence. [NIH]
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Steroids: Drugs used to relieve swelling and inflammation. [NIH] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] 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] 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] Subacute: Somewhat acute; between acute and chronic. [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 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]
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] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects
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similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] 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 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] 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] 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] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] 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] 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]
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Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [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] Thalamic Nuclei: Several groups of nuclei in the thalamus that serve as the major relay centers for sensory impulses in the brain. [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] Thermoregulation: Heat regulation. [EU] Thiothixene: A thioxanthine used as an antipsychotic agent. Its effects are similar to the phenothiazine antipsychotics. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [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] Tiapride: Benzamide derivative with dopamine antagonist actions similar to sulpiride. It has been used as an antipsychotic and in the treatment of various movement disorders. [NIH] 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] 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]
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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] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Torsades de Pointes: A ventricular tachycardia characterized by periodic twisting of the points of the QRS complexes and rates between 200 and 250 beats per minute. It may be selflimited or may progress to ventricular fibrillation. [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] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH]
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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] Trichotillomania: Compulsion to pull out one's hair. [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] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trophic: Of or pertaining to nutrition. [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] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [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] Unconditioned: An inborn reflex common to all members of a species. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Urodynamic: Measures of the bladder's ability to hold and release urine. [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] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye,
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and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [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] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] 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] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting
Dictionary 211
material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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 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] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [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] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [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]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [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] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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,
212
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usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
213
INDEX A Abdominal, 9, 151, 191, 192 Ablation, 16, 42, 151 Acceptor, 151, 191 Acepromazine, 116, 151 Acetaminophen, 121, 151 Acetylcholine, 21, 101, 107, 151, 163, 189 Acetylcholinesterase, 6, 151 Acne, 151, 201 Acoustic, 96, 102, 103, 104, 106, 151 Activities of Daily Living, 5, 71, 151 Adaptation, 151, 162, 194 Adenine, 151, 198 Adenocarcinoma, 151, 177 Adenosine, 21, 115, 151, 153, 193 Adipocytes, 151, 183 Adipose Tissue, 9, 151 Adrenal Cortex, 152, 196 Adrenal Medulla, 152, 161, 172, 190 Adrenergic, 25, 103, 152, 153, 156, 170, 172, 182, 186, 199, 205 Adverse Effect, 3, 152, 156, 164, 170, 193, 203, 211 Aerobic, 152, 179, 186 Aerosol, 152, 210 Afferent, 44, 152, 183, 194, 196, 203 Affinity, 20, 39, 41, 45, 152, 157, 164, 204 Affinity Labels, 46, 152 Agar, 152, 194 Age of Onset, 152, 209 Aggressiveness, 61, 93, 152 Agonist, 6, 18, 20, 25, 26, 29, 34, 39, 40, 46, 117, 152, 156, 160, 170, 179, 188, 190, 199, 206 Agoraphobia, 152, 179, 192 Akathisia, 152, 156 Akinesia, 21, 152 Albumin, 153, 194 Alcohol Drinking, 10, 153 Algorithms, 153, 159 Alkaline, 153, 160 Alkaloid, 153, 157, 158, 160, 164, 176, 187, 190, 199, 202 Allergen, 153, 169 Allograft, 29, 153 Alpha-1, 153 Alternative medicine, 124, 153 Amenorrhea, 153, 154, 160
Amino acid, 153, 155, 157, 159, 170, 172, 176, 179, 189, 192, 193, 195, 197, 203, 205, 207, 208, 209 Amino Acid Sequence, 153, 155 Amiodarone, 122, 153 Amitriptyline, 79, 153 Amnesia, 5, 153 Amnestic, 154, 186 Amphetamine, 16, 32, 55, 99, 103, 154, 169, 185 Ampulla, 154, 162, 172 Amygdala, 7, 32, 41, 154, 158, 183, 203, 207 Anabolic, 154, 169 Anaerobic, 154, 179 Anaesthesia, 154, 180 Anal, 89, 154 Analgesic, 25, 151, 154, 160, 183, 187, 191, 199 Analog, 32, 154, 204 Analogous, 43, 154, 195, 208 Anatomical, 19, 21, 34, 40, 41, 154, 157, 162, 180, 186 Anesthesia, 87, 154, 182, 186, 195, 196 Anesthetics, 35, 109, 154, 158, 172 Angina, 154, 155, 192 Animal model, 8, 10, 11, 21, 22, 25, 47, 96, 154 Anions, 153, 154, 182, 203, 205 Anorexia, 88, 154 Anorexia Nervosa, 88, 154 Antagonism, 21, 32, 39, 99, 154, 164 Antiallergic, 154, 196 Antianginal, 153, 155 Antiarrhythmic, 153, 155 Antibacterial, 155, 179, 182, 191, 204 Antibiotic, 154, 155, 160, 163, 172, 192, 196, 204 Antibodies, 43, 152, 155, 176, 179, 184, 194 Antibody, 43, 54, 152, 155, 164, 176, 177, 179, 180, 182, 185, 187, 199, 200, 204, 211 Anticholinergic, 153, 155, 194 Anticoagulant, 155, 197 Anticonvulsant, 155, 160, 164, 184, 193, 210 Antidopaminergic, 39, 155 Antiemetic, 155, 156, 162, 196 Antifungals, 122, 155
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Haloperidol
Antigen, 152, 155, 165, 177, 178, 179, 180, 185, 186, 199 Antihypertensive, 155, 176 Anti-infective, 155, 178, 182 Anti-inflammatory, 122, 151, 155, 202 Antimetabolite, 155, 186 Antimicrobial, 155, 163 Antineoplastic, 155, 186, 210 Antioxidant, 155, 157 Antiproliferative, 45, 155 Antipsychotic Agents, 14, 39, 116, 156, 170 Antipyretic, 151, 156, 199 Antispasmodic, 156, 191, 202 Antiviral, 122, 156 Anus, 154, 156, 181 Anxiety, 7, 16, 101, 117, 152, 156, 184, 190, 191, 192, 196, 201 Anxiolytic, 156, 186, 191 Apathy, 156, 189 Apolipoproteins, 156, 183 Apomorphine, 101, 102, 105, 156 Applicability, 15, 156 Approximate, 14, 156 Aqueous, 114, 156, 167, 171, 178 Arachidonic Acid, 40, 156, 197 Arrestin, 11, 156 Arrhythmia, 75, 155, 156 Arterial, 157, 162, 166, 178, 197, 206 Arteries, 157, 159, 167, 184, 186, 198, 207 Ascorbic Acid, 61, 157 Aspartate, 32, 48, 79, 101, 157, 182, 193 Assay, 35, 157, 179, 199 Astrocytes, 157, 186, 187 Ataxia, 15, 56, 157, 162, 179, 207 Atrial, 153, 157, 166, 209 Atrioventricular, 157, 166 Atrium, 157, 166, 209, 210 Atrophy, 43, 157 Atropine, 157, 202 Attenuated, 78, 157 Attenuation, 55, 157 Auditory, 14, 22, 102, 103, 105, 107, 157, 175, 196 Autonomic, 57, 151, 156, 157, 175, 190, 192 Autoradiography, 12, 21, 157 Autoreceptors, 39, 157 Axons, 157, 168, 181, 196, 198 B Babesiosis, 158, 199 Bacteria, 155, 158, 162, 176, 179, 185, 186, 191, 204, 208 Bactericidal, 158, 173
Bacteriophage, 158, 194, 208 Bacteriostatic, 158, 172 Barbiturate, 158, 166 Basal Ganglia, 14, 21, 24, 34, 40, 80, 156, 157, 158, 163, 178, 183, 190 Basal Ganglia Diseases, 157, 158, 163, 178 Basophils, 158, 183 Behavioral Symptoms, 4, 158 Benztropine, 68, 158 Beta-Lactamases, 158, 179 Bewilderment, 158, 165 Bicuculline, 21, 158 Bile, 158, 162, 174, 183 Bile duct, 158, 162 Biliary, 121, 158, 162 Binaural, 14, 158 Binding Sites, 48, 75, 158 Biochemical, 11, 19, 26, 35, 40, 42, 53, 155, 159, 203 Biogenic Monoamines, 159, 183 Biosynthesis, 156, 159, 203 Biotechnology, 48, 49, 124, 135, 159 Bladder, 159, 163, 165, 180, 209 Blastocyst, 159, 194 Blood Coagulation, 159, 160, 207 Blood Glucose, 159, 178, 181 Blood Platelets, 159, 203 Blood pressure, 155, 159, 161, 162, 178, 182, 187, 198, 204 Blood vessel, 159, 160, 161, 162, 166, 175, 182, 184, 203, 205, 207, 210 Blood-Brain Barrier, 159, 183, 194, 206 Blot, 34, 45, 159 Body Composition, 9, 159 Body Fluids, 159, 204 Bone Marrow, 159, 167, 184, 187 Bowel, 154, 159 Brachytherapy, 159, 181, 182, 199, 211 Bradykinin, 160, 194 Brain Stem, 160, 162, 166 Broad-spectrum, 160, 191 Bromocriptine, 96, 102, 160 Burns, 52, 121, 160 Burns, Electric, 160 Butorphanol, 25, 160 C Calcium, 44, 122, 160, 165 Calcium channel blocker, 122, 160 Calcium Channel Blockers, 122, 160 Cannabis, 96, 99, 160 Canonical, 54, 160 Carbamazepine, 58, 76, 87, 160
215
Carbohydrate, 160, 175, 176 Carbon Dioxide, 160, 168, 194, 201 Carcinoma, 161 Cardiac, 91, 155, 161, 163, 166, 172, 173, 186, 188, 199 Cardiorespiratory, 161, 186 Cardiovascular, 9, 55, 154, 161, 203 Cardiovascular disease, 9, 161 Carrier Proteins, 161, 194, 199 Case report, 161, 164 Case series, 161, 164 Catalepsy, 20, 48, 54, 59, 68, 101, 104, 105, 106, 161 Catecholamine, 7, 161, 170, 193 Caudal, 161, 169, 174, 178, 190, 195, 198 Caudate Nucleus, 107, 158, 161, 167, 188, 190 Cell Cycle, 161, 164, 210 Cell Division, 158, 161, 185, 194, 196 Cell membrane, 160, 161, 169, 174, 193, 195, 204, 211 Cell proliferation, 43, 161 Cerebellar, 56, 157, 161, 162, 200, 209 Cerebellar Diseases, 157, 162, 209 Cerebellum, 15, 161, 162, 167, 200 Cerebral Cortex, 19, 101, 157, 162, 173, 188, 198 Cerebrovascular, 158, 160, 161, 162, 207 Cerebrum, 162, 167, 206 Cervical, 162, 208 Chaperonins, 162, 187 Character, 162, 168, 176 Chemoreceptor, 156, 162 Chin, 162, 185 Chlorpromazine, 38, 71, 101, 103, 107, 116, 122, 162, 174, 185, 192, 193, 196 Chlorprothixene, 116, 162 Cholangitis, 122, 162 Cholestasis, 122, 162 Cholesterol, 158, 162, 163, 167, 171, 178, 183, 184, 206 Cholesterol Esters, 162, 183 Choline, 11, 54, 151, 163 Cholinergic, 6, 11, 24, 103, 153, 156, 163, 190, 203 Cholinesterase Inhibitors, 6, 163 Chorea, 58, 156, 163 Choreatic Disorders, 163 Chromatin, 163, 172, 189 Chromosomal, 35, 163 Chromosome, 163, 183 Chylomicrons, 163, 183
Cilastatin, 163, 179 Cinchona, 163, 199 Ciprofloxacin, 122, 163 Circadian, 69, 100, 163 Circadian Rhythm, 100, 163 Cisplatin, 163, 191 Citalopram, 103, 164 Clinical study, 39, 164, 166 Clinical trial, 6, 17, 41, 47, 52, 135, 164, 166, 167, 170, 188, 197, 200 Clomipramine, 56, 84, 86, 164 Clonazepam, 54, 90, 164 Clonic, 79, 164, 166 Cloning, 159, 164 Coca, 164 Cocaine, 16, 20, 28, 45, 164, 174, 185 Coenzyme, 157, 164 Cofactor, 164, 197, 207 Cognition, 21, 23, 24, 164, 189 Complement, 164, 165, 194 Complementary and alternative medicine, 99, 109, 165 Complementary medicine, 99, 165 Compliance, 49, 78, 88, 116, 165 Compulsions, 165, 190 Computational Biology, 135, 165 Concomitant, 7, 73, 115, 117, 165 Confounding, 19, 165 Confusion, 125, 165, 169, 178, 189 Congenita, 165, 199 Congestion, 156, 165 Conjugated, 165, 167, 176 Conjunctiva, 166, 194, 209 Connective Tissue, 157, 159, 166, 169, 173, 174 Consciousness, 154, 166, 168, 170, 197 Constipation, 156, 166, 176 Constrict, 38, 166 Consultation, 12, 166 Contraindications, ii, 166 Contralateral, 166, 185, 200 Control group, 41, 166 Controlled clinical trial, 87, 166 Controlled study, 86, 118, 166 Convulsants, 122, 166 Convulsions, 155, 158, 166, 171, 178 Coordination, 162, 166, 198 Cor, 31, 166 Corneum, 82, 97, 166, 172 Coronary, 161, 167, 186, 192 Coronary heart disease, 161, 167 Coronary Thrombosis, 167, 186
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Haloperidol
Corpus, 167, 175, 184, 188, 196 Corpus Luteum, 167, 184, 196 Corpus Striatum, 167, 175, 188 Cortex, 7, 14, 19, 35, 40, 41, 100, 167, 172, 175, 196, 200 Cortical, 19, 35, 37, 38, 42, 47, 167, 173, 196, 198, 202, 207 Cortices, 41, 45, 167 Cranial, 162, 167, 175, 190, 192, 209 Critical Care, 70, 74, 82, 167 Cues, 22, 46, 167 Curative, 167, 189, 207 Cyclosporine, 122, 167 Cytochrome, 63, 67, 71, 72, 74, 96, 167 Cytoplasm, 158, 161, 167, 168, 172, 187, 189, 206 Cytoskeletal Proteins, 34, 168 Cytoskeleton, 30, 168 Cytotoxic, 122, 168, 191, 200 Cytotoxic chemotherapy, 168, 191 D Decarboxylation, 159, 168, 177, 188 Decidua, 168, 194 Decision Making, 22, 41, 168 Degenerative, 125, 140, 168, 177 Dehydration, 78, 168 Deletion, 16, 168 Delirium, 5, 82, 90, 156, 168 Delusions, 39, 168, 198 Dementia, 3, 4, 5, 6, 38, 60, 69, 86, 87, 140, 156, 168 Dendrites, 44, 47, 168, 189, 198 Dendritic, 23, 48, 168 Density, 20, 23, 38, 41, 168, 171, 183, 191 Dentate Gyrus, 16, 168, 177 Depolarization, 34, 169 Depressive Disorder, 42, 169, 183 Dermatitis, 58, 169 Dermis, 169, 208 Desensitization, 10, 40, 169 Dextroamphetamine, 154, 169, 186 Diabetes Mellitus, 9, 169, 175 Diabetic Ketoacidosis, 9, 169 Diagnostic procedure, 113, 124, 169 Diastolic, 169, 176, 178 Diastolic blood pressure, 169, 176 Diencephalon, 169, 172, 174, 178, 196, 206, 207 Digestion, 158, 159, 169, 183, 205, 210 Dihydrotestosterone, 169, 200 Direct, iii, 8, 14, 15, 19, 36, 42, 54, 127, 169, 170, 199, 200, 206
Discrimination, 18, 28, 169 Disinfectant, 169, 173 Disorientation, 165, 168, 169 Dissociation, 152, 169 Domesticated, 170, 176 Dopa, 6, 122, 170, 183 Dopamine Agonists, 20, 170 Dopamine Antagonists, 20, 170 Dose-dependent, 35, 65, 170 Double-blind, 3, 8, 13, 17, 24, 49, 50, 56, 57, 61, 63, 64, 82, 83, 85, 86, 88, 92, 93, 96, 99, 111, 170 Drive, ii, vi, 27, 95, 97, 170 Drug Delivery Systems, 118, 170 Drug Interactions, 128, 170 Drug Monitoring, 71, 73, 77, 83, 85, 170 Drug Tolerance, 170, 207 Drug Toxicity, 161, 170, 197 Duodenum, 158, 171, 172, 189, 205 Dyskinesia, 8, 11, 51, 54, 72, 77, 78, 84, 93, 96, 102, 106, 115, 156, 164, 171 Dyslipidemia, 9, 89, 171 Dysphoric, 169, 171 E Effector, 151, 165, 171, 193 Efficacy, 3, 4, 6, 8, 10, 13, 17, 21, 23, 32, 38, 39, 50, 53, 55, 56, 57, 58, 63, 73, 76, 79, 89, 91, 116, 171, 179, 184 Elastic, 171, 176 Electroconvulsive Therapy, 91, 171 Electrolyte, 168, 171, 195, 204 Electrons, 155, 171, 182, 191, 199, 200 Embryo, 30, 159, 171, 180, 195 Emergency Treatment, 73, 171 Emesis, 117, 156, 171, 195 Emetic, 156, 171 Empirical, 8, 21, 38, 171 Emulsion, 157, 171 Endogenous, 11, 28, 29, 84, 117, 170, 171, 172, 197 Endorphins, 172, 189 Endoscopic, 172, 186 Energy balance, 172, 183 Enhancers, 82, 172 Enkephalin, 21, 48, 97, 172 Entorhinal Cortex, 172, 177 Environmental Health, 134, 136, 172 Enzymatic, 153, 159, 160, 165, 172, 177, 201 Enzyme Inhibitors, 172, 194 Eosinophils, 172, 183 Epidermis, 166, 169, 172 Epinephrine, 152, 170, 172, 189, 190, 209
217
Epithalamus, 169, 172, 183 Ergot, 160, 172 Erythrocytes, 158, 159, 172, 200 Erythromycin, 122, 172 Estrogen, 173, 196, 202, 206 Ethanol, 32, 35, 70, 82, 97, 102, 164, 173 Eukaryotic Cells, 168, 173, 180, 191 Evoke, 173, 205 Excitability, 45, 173, 199 Excitation, 40, 162, 173, 189 Excitatory, 23, 27, 33, 47, 173, 175, 176, 179 Exhaustion, 154, 173 Exogenous, 11, 170, 171, 173, 197, 209 External-beam radiation, 173, 182, 199, 211 Extracellular, 21, 39, 44, 48, 157, 166, 173, 186, 204 Extracellular Space, 173, 186 F Facial, 100, 173 Facial Pain, 100, 173 Family Planning, 135, 173 Fat, 9, 151, 156, 159, 166, 167, 173, 182, 183, 209 Fetus, 173, 179, 194, 196, 209 Fibrinogen, 173, 194, 207 Fibrosis, 122, 173 Fissure, 168, 173, 196 Flatus, 173, 174 Flunitrazepam, 73, 173 Fluoxetine, 16, 65, 174 Flupenthixol, 116, 174 Fluphenazine, 29, 47, 92, 116, 174 Fluspirilene, 116, 174 Fossa, 162, 174 Frontal Lobe, 41, 72, 174, 196 Functional magnetic resonance imaging, 80, 105, 174 Fungi, 155, 174, 186, 211 G GABA, 15, 19, 21, 34, 35, 38, 40, 48, 54, 158, 164, 174, 188, 210 Gallbladder, 151, 158, 174 Ganglia, 14, 21, 34, 151, 158, 174, 188, 192 Gap Junctions, 174, 206 Gas, 59, 67, 160, 173, 174, 178, 190, 210 Gastric, 174, 177, 200 Gastrin, 174, 177 Gastrointestinal, 160, 163, 164, 172, 173, 174, 200, 203, 205 Gastrointestinal tract, 163, 164, 173, 174, 203
Gene, 16, 17, 26, 28, 29, 44, 45, 48, 67, 69, 159, 174, 194 Gene Duplication, 69, 174 Gene Expression, 26, 29, 45, 48, 174 Geniculate Bodies, 174, 198 Genital, 163, 175 Genotype, 26, 71, 175, 193 Geriatric, 3, 4, 5, 12, 55, 82, 86, 91, 175 Geriatric Psychiatry, 3, 4, 12, 82, 86, 91, 175 Gestation, 175, 194 Ginkgo biloba, 99, 104, 107, 175 Ginseng, 109, 175 Gland, 152, 175, 191, 202, 205, 207 Globus Pallidus, 21, 38, 44, 158, 167, 175 Glomeruli, 30, 175 Glomerulus, 175 Glossopharyngeal Nerve, 173, 175 Glucose, 9, 55, 68, 157, 159, 169, 175, 178, 180, 181 Glucose Intolerance, 169, 175 Glucose tolerance, 9, 175 Glucose Tolerance Test, 175 Glutamate, 19, 28, 30, 32, 34, 36, 40, 44, 48, 60, 107, 175, 176, 182, 185 Glutamic Acid, 19, 176, 189 Gluten, 92, 176 Glycine, 109, 153, 176, 189, 203 Glycoproteins, 176, 182, 195, 204 Gonadotropin, 65, 176 Governing Board, 176, 195 Gram-negative, 176, 179, 191 Gram-positive, 176, 179, 191 Granule, 168, 176 Guanfacine, 6, 176 Guinea Pigs, 101, 176 Gyrus Cinguli, 176, 183 H Habituation, 103, 176 Haematemesis, 171, 176 Half-Life, 47, 176 Hallucinogen, 176, 193 Haptens, 152, 176, 199 Harmaline, 13, 176 Heart attack, 161, 176 Heat-Shock Proteins, 176, 177, 187 Heat-Shock Proteins 90, 177, 187 Heme, 167, 177 Hemorrhage, 177, 205 Hemostasis, 177, 203 Hepatic, 122, 153, 168, 175, 177, 187 Hepatitis, 122, 177, 192
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Haloperidol
Hepatocellular, 122, 177 Hepatocellular carcinoma, 122, 177 Hepatocyte, 162, 177 Heredity, 174, 177 Heterogeneity, 45, 152, 177 Hiccup, 162, 170, 177 Hippocampus, 15, 16, 28, 36, 43, 101, 168, 177, 183, 198, 203, 205 Histamine, 71, 156, 177, 186, 196, 200 Histocompatibility, 115, 177 Homologous, 10, 177, 206 Hormonal, 157, 177 Hormone, 31, 157, 163, 172, 174, 177, 181, 182, 183, 196, 207 Human Activities, 24, 177 Hybrid, 30, 177 Hydrogen, 151, 160, 177, 178, 187, 189, 191, 205 Hydrogen Peroxide, 178, 205 Hydrolysis, 151, 158, 163, 178, 183, 195 Hydrophobic, 115, 178, 183 Hypercholesterolemia, 171, 178 Hyperglycemia, 9, 178 Hyperlipidemia, 171, 178 Hypersensitivity, 153, 169, 178 Hypertension, 160, 161, 178, 182 Hyperthermia, 65, 121, 177, 178 Hypertriglyceridemia, 171, 178 Hypertrophy, 166, 178, 209 Hypnotherapy, 104, 178 Hypnotic, 158, 178, 184, 186 Hypoglycaemia, 168, 178 Hypoglycemic, 122, 178 Hypoglycemic Agents, 122, 178 Hypokinesia, 178, 192 Hypotension, 56, 156, 166, 178, 189 Hypothalamic, 31, 178 Hypothalamus, 169, 172, 178, 183, 189, 203 Hypothermia, 121, 178 Hypotonia, 13, 162, 163, 179 Hypoxia, 168, 179, 207 I Ibotenic Acid, 179, 188 Ileum, 179, 189 Imaging procedures, 179, 208 Imidazole, 177, 179, 200 Imipenem, 56, 163, 179 Imipramine, 115, 164, 179 Immune function, 29, 179 Immune response, 155, 176, 179, 205, 211 Immune system, 30, 179, 184, 211 Immune Tolerance, 29, 179
Immunoassay, 83, 84, 179 Immunofluorescence, 12, 179 Immunogenic, 179, 199 Immunoglobulin, 155, 179, 187 Immunohistochemistry, 42, 179 Immunologic, 179, 200 Immunology, 152, 179 Immunosuppressant, 45, 179, 186 Immunosuppressive, 29, 45, 71, 179, 180 Immunotherapy, 169, 179 Impairment, 11, 17, 30, 36, 61, 157, 158, 162, 168, 171, 180, 185, 198 Implant radiation, 180, 181, 182, 199, 211 Impotence, 70, 180 In situ, 12, 16, 31, 34, 45, 180 In Situ Hybridization, 12, 16, 34, 45, 180 In vitro, 7, 20, 28, 40, 47, 61, 72, 101, 180 In vivo, 7, 44, 47, 72, 75, 88, 115, 180, 186, 207 Incontinence, 180, 202 Induction, 16, 29, 30, 36, 156, 180, 182, 196 Infarction, 156, 167, 180, 186 Infection, 162, 168, 179, 180, 184, 189, 192, 205, 211 Infertility, 160, 180 Inflammation, 151, 153, 155, 162, 169, 173, 177, 180, 195, 205, 209 Infusion, 31, 37, 46, 58, 101, 180 Ingestion, 27, 175, 180, 195 Inhalation, 152, 177, 180, 195 Initiation, 180, 184 Innervation, 36, 180 Inositol, 180, 185 Inotropic, 170, 181 Inpatients, 80, 86, 107, 181 Insight, 7, 26, 32, 44, 181 Insulin, 9, 169, 175, 181, 182, 209 Insulin-dependent diabetes mellitus, 181 Interleukin-1, 71, 181 Interleukin-2, 181 Internal radiation, 181, 182, 199, 211 Interneurons, 27, 181 Interstitial, 159, 173, 181, 182, 201, 211 Intestinal, 68, 175, 181 Intestines, 151, 174, 181 Intoxication, 22, 168, 181, 211 Intracellular, 29, 160, 180, 181, 185, 195, 200 Intramuscular, 50, 51, 58, 61, 73, 89, 181 Intrathecal, 87, 181 Intravenous, 46, 56, 70, 74, 89, 91, 180, 181 Intrinsic, 23, 39, 152, 181
219
Invasive, 181, 184 Involuntary, 5, 158, 163, 181, 188, 200, 204 Iodine, 20, 181 Ion Channels, 45, 157, 182, 193, 206 Ions, 169, 171, 178, 182, 195, 204 Irradiation, 16, 182, 211 Ischemia, 157, 182 Isoenzymes, 74, 182 Isoniazid, 122, 182 K Kainate, 36, 182 Kb, 134, 182 Ketamine, 27, 32, 35, 73, 79, 182, 193 Ketanserin, 103, 182 Ketone Bodies, 169, 182 Ketosis, 169, 182 Kinetic, 20, 74, 85, 182 L Lactation, 182, 196 Latent, 99, 100, 104, 105, 107, 182 Leptin, 92, 183 Lesion, 34, 101, 183, 184, 206 Leukocytes, 59, 158, 159, 172, 183, 187, 189 Levo, 170, 183 Levodopa, 170, 183 Ligands, 17, 29, 41, 45, 183 Limbic, 7, 27, 32, 35, 37, 38, 48, 154, 176, 183, 196 Limbic System, 27, 154, 176, 183, 196 Linkage, 45, 183 Lip, 117, 183 Lipid, 9, 156, 163, 181, 183, 186, 209 Lipolysis, 9, 183 Lipoprotein, 89, 171, 176, 183, 184 Lithium, 49, 53, 76, 86, 96, 97, 124, 156, 183 Lithium Carbonate, 53, 183 Liver, 9, 65, 72, 121, 151, 153, 156, 158, 164, 171, 174, 175, 177, 183, 184, 187, 211 Liver cancer, 122, 183 Liver Neoplasms, 183, 211 Loading dose, 74, 184 Lobe, 15, 42, 97, 184 Localization, 47, 179, 184 Localized, 32, 180, 184, 187, 194 Locomotion, 16, 20, 184, 194 Locomotor, 21, 117, 184 Long-Term Potentiation, 30, 184 Lorazepam, 32, 51, 92, 184 Low-density lipoprotein, 171, 183, 184 Loxapine, 4, 116, 184 Lutein Cells, 184, 196 Lymphatic, 180, 184, 194, 204
Lymphatic system, 184, 204 Lymphocyte, 155, 184, 185 Lymphoid, 155, 184 M Macrophage, 181, 184 Magnetic Resonance Imaging, 9, 184 Maintenance therapy, 47, 116, 184 Malignant, 52, 65, 70, 80, 151, 155, 183, 184, 200 Malnutrition, 153, 157, 184 Mammary, 185, 206 Mania, 47, 49, 56, 68, 76, 86, 124, 185 Manic, 156, 183, 185, 198 Mazindol, 29, 185 Medial, 14, 15, 32, 101, 175, 176, 185, 198, 203 Mediate, 28, 35, 38, 39, 43, 45, 46, 170, 185, 187, 200 Mediator, 21, 170, 181, 185, 203 MEDLINE, 135, 185 Meiosis, 185, 206 Melanin, 185, 193, 209 Memory, 11, 12, 21, 22, 24, 36, 42, 55, 78, 111, 117, 123, 125, 153, 154, 168, 184, 185 Meninges, 161, 185 Mental Disorders, 15, 39, 42, 178, 185, 197, 198 Mental Health, iv, 5, 24, 97, 104, 134, 136, 175, 185, 198 Mental Processes, 169, 185, 197 Mental Retardation, 55, 185 Mesencephalic, 40, 185, 200 Mesolimbic, 10, 16, 20, 32, 46, 47, 156, 185, 210 Mesoridazine, 116, 185 Metabolic acidosis, 169, 185 Metabolite, 52, 164, 185 Metabotropic, 30, 36, 185 Methamphetamine, 22, 26, 185 Methotrexate, 58, 122, 186 Methylphenidate, 24, 186 MI, 115, 149, 186 Mianserin, 53, 186 Microbe, 186, 208 Microbiology, 151, 157, 186 Microdialysis, 22, 33, 40, 44, 186 Microglia, 43, 157, 186, 187 Microorganism, 164, 186, 211 Midazolam, 49, 70, 85, 186 Mitochondria, 162, 186, 191 Mitochondrial Swelling, 186, 188 Mitotic, 186, 210
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Haloperidol
Modification, 100, 153, 186 Modulator, 117, 187 Molecular Chaperones, 7, 162, 177, 187 Molecule, 26, 155, 159, 164, 165, 169, 171, 173, 178, 187, 191, 200, 210 Monitor, 187, 190 Monoamine, 47, 100, 154, 169, 176, 187 Monoamine Oxidase, 154, 169, 176, 187 Monoclonal, 54, 182, 187, 199, 211 Monocytes, 181, 183, 187 Mononuclear, 59, 76, 187 Monotherapy, 37, 84, 187 Mood Disorders, 7, 187 Morphine, 87, 101, 106, 156, 187, 188, 191 Morphological, 15, 19, 23, 34, 43, 171, 187 Morphology, 15, 34, 187 Motility, 187, 203 Motion Perception, 63, 187 Motion Sickness, 187, 188, 196, 202 Motor Activity, 3, 20, 27, 39, 48, 51, 117, 166, 187, 197, 198 Mucosa, 188, 196 Multicenter study, 8, 32, 188 Multidose, 50, 188 Muscimol, 40, 188 Mutate, 18, 188 Mydriatic, 188, 202 Myocardium, 186, 188 Myotonia, 188, 199 N Nalbuphine, 25, 188 Naltrexone, 32, 188 Narcolepsy, 169, 186, 188 Narcotic, 160, 187, 188 Nausea, 155, 156, 182, 188, 191, 192 Necrosis, 114, 121, 180, 186, 188, 201 Neocortex, 15, 19, 23, 188 Neoplastic, 173, 188 Neostriatum, 161, 167, 188 Nerve Growth Factor, 11, 188 Nervous System, 24, 45, 74, 122, 151, 152, 154, 161, 163, 164, 169, 174, 176, 183, 185, 186, 187, 188, 189, 192, 194, 197, 202, 203, 205, 206, 210 Neural, 8, 23, 24, 36, 41, 46, 82, 96, 152, 186, 187, 189, 203, 204 Neuroanatomy, 24, 183, 189 Neuromuscular, 151, 189 Neuromuscular Junction, 151, 189 Neuronal, 11, 16, 39, 43, 67, 164, 189 Neuropathy, 189, 192 Neuropeptide, 31, 189
Neurophysiology, 169, 189 Neuropsychology, 12, 189 Neurotensin, 35, 47, 189 Neurotoxic, 35, 52, 179, 188, 189 Neutrons, 182, 189, 199 Neutrophils, 183, 189 Niacin, 122, 189, 209 Nicotine, 33, 36, 70, 81, 190 Nitrogen, 153, 190, 209 Nonverbal Communication, 190, 198 Norepinephrine, 6, 152, 153, 170, 189, 190 Nuclear, 19, 158, 171, 173, 183, 188, 190, 207 Nuclei, 19, 40, 154, 171, 172, 184, 189, 190, 194, 198, 203, 207 Nucleic acid, 180, 190, 198 Nucleus Accumbens, 7, 11, 16, 32, 47, 190, 210 O Observational study, 62, 190 Obsessive-Compulsive Disorder, 26, 117, 190 Oculogyric, 58, 190 Oculomotor, 185, 190 Odds Ratio, 190, 200 Ofloxacin, 91, 191 Oncology, 122, 191 Ondansetron, 99, 191 Opacity, 168, 191 Opiate, 32, 172, 187, 191 Opium, 187, 191 Organelles, 34, 167, 168, 187, 191, 194 Orofacial, 102, 106, 173, 191 Orthostatic, 156, 191 Osmosis, 191 Osmotic, 114, 153, 186, 191, 203 Outpatient, 116, 191 Overdose, 69, 75, 166, 191 Ovum, 167, 168, 175, 191, 196 Oxidation, 74, 96, 97, 151, 155, 167, 169, 191 P Palliative, 58, 69, 191, 207 Palsy, 55, 191 Pancreas, 151, 181, 191 Panic, 66, 179, 191, 192 Panic Disorder, 179, 192 Paralysis, 152, 185, 192 Parietal, 14, 192 Parietal Lobe, 192 Parkinsonism, 21, 38, 40, 156, 183, 192 Partial remission, 192, 201
221
Particle, 192, 208 Parturition, 192, 196 Patch, 192, 208 Pathogenesis, 6, 192 Pathologies, 121, 192 Pathophysiology, 33, 34, 40, 48, 192 Patient Compliance, 116, 192 Penfluridol, 75, 116, 192 Penicillin, 154, 192 Peptide, 16, 153, 183, 192, 195, 197 Perazine, 74, 116, 192 Perception, 22, 192, 202 Perhexiline, 122, 192 Peripheral Nervous System, 189, 191, 192, 196, 205 Perphenazine, 116, 193 Pharmaceutical Preparations, 173, 193, 197 Pharmacodynamic, 14, 193 Pharmacokinetic, 14, 59, 83, 96, 105, 193 Pharmacologic, 40, 154, 173, 176, 193, 208 Pharmacology, Clinical, 12, 193 Pharmacotherapy, 32, 39, 52, 56, 58, 80, 86, 90, 91, 193 Phencyclidine, 27, 35, 193 Phenotype, 15, 193 Phenyl, 117, 193 Phenylalanine, 193, 209 Phenytoin, 160, 193 Phosphodiesterase, 193, 202 Phospholipids, 173, 181, 183, 193 Phosphorus, 122, 160, 193, 194 Phosphorylated, 7, 156, 164, 193 Phosphorylation, 7, 193 Phototransduction, 156, 194 Physiologic, 152, 159, 170, 176, 178, 194, 200, 209 Physostigmine, 13, 24, 194 Pigment, 83, 194 Pilot study, 50, 194 Placenta, 29, 194, 196 Plants, 153, 157, 158, 161, 163, 164, 175, 187, 190, 194, 195, 202, 208, 210 Plaque, 6, 194 Plasma, 31, 45, 54, 62, 63, 65, 67, 69, 71, 73, 74, 75, 77, 85, 86, 87, 89, 91, 153, 155, 161, 162, 173, 175, 177, 194, 203 Plasma cells, 155, 194 Plasma protein, 89, 153, 194, 203 Plasticity, 7, 10, 30, 44, 194 Plastids, 162, 191, 194 Platelet Aggregation, 182, 194, 207
Pleomorphic, 190, 194 Plexus, 55, 194 Pneumonia, 166, 195 Poisoning, 50, 156, 168, 171, 172, 181, 188, 195 Pollen, 195, 199 Polymerase, 30, 195 Polymorphic, 168, 195 Polymorphism, 67, 75, 195 Polypeptide, 153, 173, 195, 196, 212 Portal Pressure, 195, 202 Posterior, 154, 157, 162, 172, 175, 191, 195 Postnatal, 20, 195 Postoperative, 25, 87, 195 Postoperative Nausea and Vomiting, 87, 195 Postsynaptic, 26, 48, 195, 206 Post-synaptic, 30 Post-synaptic, 195 Postural, 106, 195 Potassium, 46, 98, 195, 199 Potassium Channels, 46, 195 Potentiates, 68, 96, 181, 195 Potentiating, 153, 195 Potentiation, 163, 184, 195 Practice Guidelines, 136, 195 Preclinical, 18, 32, 33, 195 Precursor, 156, 163, 170, 171, 172, 183, 190, 193, 196, 209 Prefrontal Cortex, 19, 23, 41, 48, 101, 196 Pregnancy Maintenance, 196 Premedication, 196, 202 Prenatal, 111, 171, 196 Presynaptic, 33, 38, 157, 189, 196, 206 Presynaptic Terminals, 157, 196, 206 Probe, 186, 196 Procaine, 153, 196 Progesterone, 29, 196 Progression, 45, 154, 196 Progressive, 168, 170, 188, 196, 201 Projection, 16, 23, 28, 181, 190, 196, 198, 200, 210 Prolactin, 52, 53, 57, 58, 68, 72, 83, 84, 85, 92, 115, 160, 196 Promazine, 116, 196 Promethazine, 49, 71, 85, 196 Prophase, 196, 206 Prophylaxis, 87, 116, 196, 197, 201 Propylene Glycol, 82, 197 Prospective study, 79, 197 Prostaglandins, 156, 197 Protective Agents, 160, 197
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Haloperidol
Protein Binding, 51, 197 Protein C, 18, 27, 153, 156, 158, 183, 197 Protein S, 159, 172, 197 Protocol, 6, 197 Pruritus, 156, 196, 197 Psoriasis, 197, 201 Psychic, 185, 197, 202 Psychoactive, 29, 197, 211 Psychology, 12, 17, 21, 22, 46, 96, 165, 169, 189, 197 Psychomotor, 4, 57, 62, 72, 160, 168, 189, 197, 198 Psychomotor Agitation, 4, 197 Psychomotor Performance, 62, 198 Psychopathology, 5, 7, 124, 198 Psychophysiology, 55, 189, 198 Psychotherapy, 104, 198 Psychotomimetic, 154, 169, 198 Public Health, 28, 136, 198 Public Policy, 135, 198 Publishing, 48, 198 Pulmonary, 159, 166, 198, 210 Pulmonary hypertension, 166, 198 Pulvinar, 19, 198 Purines, 198, 203 Pyramidal Cells, 28, 168, 198 Pyramidal Tracts, 173, 198 Pyrimidines, 198, 203 Q Quaternary, 199, 202 Quercetin, 106, 199 Quiescent, 29, 199 Quinidine, 85, 122, 163, 199 Quinine, 122, 163, 199 Quinpirole, 40, 199 R Race, 170, 199 Racemic, 170, 199 Raclopride, 116, 199 Radiation, 157, 173, 178, 179, 181, 182, 199, 200, 211 Radiation therapy, 173, 181, 182, 199, 211 Radioactive, 157, 176, 178, 180, 181, 182, 190, 199, 211 Radioimmunoassay, 84, 199 Radioisotope, 199, 208 Radiolabeled, 20, 41, 182, 199, 211 Radiological, 16, 37, 199 Radiology, 19, 37, 200 Radiotherapy, 159, 182, 199, 200, 211 Randomized, 4, 5, 8, 13, 17, 32, 50, 51, 56, 57, 62, 85, 86, 88, 96, 99, 100, 171, 200
Ranitidine, 122, 200 Reaction Time, 12, 13, 96, 200 Reactivation, 58, 200 Reality Testing, 198, 200 Receptors, Serotonin, 200, 203 Recombinant, 7, 46, 72, 200, 210 Rectum, 156, 173, 174, 180, 200 Recurrence, 163, 200 Red blood cells, 75, 172, 200, 203 Red Nucleus, 157, 200, 210 Reductase, 74, 186, 200 Refer, 1, 164, 172, 174, 175, 181, 184, 189, 198, 200, 208 Reflex, 26, 46, 103, 200, 209 Refractory, 13, 56, 71, 104, 107, 200 Regimen, 5, 14, 74, 171, 192, 193, 200 Relapse, 8, 63, 123, 200 Relative risk, 24, 200 Reliability, 41, 83, 201 Remission, 66, 184, 200, 201 Remoxipride, 84, 116, 201 Renal failure, 168, 201 Respiration, 161, 162, 166, 186, 187, 201 Response rate, 4, 201 Retinal, 156, 194, 201 Retinoids, 122, 201 Retrospective, 79, 201 Rhabdomyolysis, 70, 201 Rhodopsin, 156, 201 Ribonuclease, 26, 201 Ribose, 151, 201 Risk factor, 197, 200, 201 Ritanserin, 49, 86, 107, 201 Rods, 156, 194, 201, 202 Rolipram, 44, 202 Rutin, 199, 202 S Salicylate, 202 Salicylic, 202 Salicylic Acids, 202 Saline, 46, 202 Schizoid, 202, 211 Schizophrenia, 6, 9, 10, 11, 12, 13, 14, 15, 17, 19, 23, 25, 27, 30, 32, 33, 34, 35, 36, 37, 39, 41, 42, 44, 45, 47, 48, 49, 50, 51, 52, 53, 54, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 69, 70, 71, 73, 74, 75, 76, 77, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 92, 93, 99, 100, 104, 105, 106, 107, 108, 111, 114, 115, 117, 118, 140, 156, 161, 171, 174, 184, 192, 201, 202, 204, 210, 211 Schizotypal Personality Disorder, 202, 211
223
Scopolamine, 24, 96, 202 Screening, 101, 164, 202 Secretion, 85, 160, 163, 177, 181, 182, 186, 200, 202, 210 Secretory, 202, 206 Sedative, 153, 158, 179, 184, 186, 196, 202 Seizures, 79, 160, 164, 168, 193, 202 Selective estrogen receptor modulator, 202, 206 Self Care, 151, 202 Semisynthetic, 160, 179, 202 Senile, 156, 202 Septal, 183, 202, 203 Septal Nuclei, 183, 203 Serine, 7, 203 Serologic, 179, 203 Sertraline, 90, 203 Serum, 51, 57, 64, 73, 85, 92, 115, 153, 164, 176, 179, 184, 199, 203 Serum Albumin, 199, 203 Sex Characteristics, 203, 207 Shock, 35, 162, 203, 208 Signs and Symptoms, 200, 201, 203 Skeletal, 9, 163, 179, 199, 201, 203, 204 Skeleton, 203 Skull, 203, 206 Sleep Deprivation, 87, 203 Sludge, 122, 203 Small intestine, 163, 171, 177, 179, 181, 203 Smooth muscle, 160, 177, 187, 203, 204, 205 Social Behavior, 41, 204 Sodium, 60, 91, 101, 122, 194, 199, 204, 210 Sodium Channels, 194, 199, 204, 210 Solvent, 118, 173, 191, 197, 204 Soma, 198, 204 Somatic, 41, 175, 183, 185, 192, 196, 204 Spasm, 156, 177, 185, 204 Specialist, 141, 204 Species, 31, 59, 65, 78, 170, 172, 175, 176, 177, 185, 187, 199, 204, 205, 209, 211 Specificity, 28, 41, 152, 204 Spectrum, 179, 186, 204 Sperm, 96, 163, 195, 204 Sperm Motility, 96, 204 Spermatozoon, 204 Spinal cord, 157, 160, 161, 162, 166, 181, 185, 188, 189, 192, 198, 200, 204 Spiperone, 116, 204 Spleen, 75, 184, 204 Stabilizer, 56, 204 Steady state, 14, 204
Stereotypy, 117, 204 Steroids, 75, 152, 205 Stimulant, 70, 154, 169, 176, 177, 185, 186, 205, 206 Stimulus, 14, 18, 28, 104, 170, 173, 180, 182, 200, 205, 207 Stomach, 151, 174, 175, 177, 181, 182, 188, 203, 204, 205 Strand, 195, 205 Stress, 7, 43, 161, 162, 188, 205 Striatum, 7, 11, 16, 21, 26, 32, 34, 37, 40, 44, 48, 188, 190, 205 Stroke, 35, 42, 134, 161, 205 Structure-Activity Relationship, 20, 205 Subacute, 14, 180, 205 Subclinical, 180, 202, 205 Subcutaneous, 58, 151, 205 Subiculum, 177, 205 Subspecies, 204, 205 Substance P, 172, 185, 202, 205 Superoxide, 107, 205 Superoxide Dismutase, 107, 205 Supplementation, 106, 205 Suppression, 10, 21, 29, 107, 205 Suppressive, 8, 205 Sympathomimetic, 154, 169, 170, 172, 185, 190, 205 Symptomatic, 24, 158, 206 Symptomatic treatment, 158, 206 Symptomatology, 43, 114, 206 Synapse, 152, 189, 196, 206, 208 Synaptic, 23, 28, 30, 34, 47, 184, 189, 190, 206 Synaptic Transmission, 190, 206 Synaptic Vesicles, 206 Synergistic, 196, 206 Systemic, 16, 22, 27, 36, 37, 44, 122, 128, 159, 168, 172, 180, 182, 199, 206, 209, 210, 211 Systolic, 176, 178, 206 T Tachycardia, 206, 208 Tacrine, 122, 206 Tamoxifen, 122, 202, 206 Tardive, 8, 11, 51, 54, 72, 77, 84, 93, 96, 115, 156, 164, 206 Telencephalon, 158, 162, 206 Temporal, 11, 14, 19, 24, 32, 45, 154, 177, 206, 207 Temporal Lobe, 14, 32, 154, 207 Testosterone, 200, 207 Thalamic, 19, 35, 157, 172, 207
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Haloperidol
Thalamic Diseases, 157, 207 Thalamic Nuclei, 19, 172, 207 Thalamus, 19, 35, 40, 167, 169, 172, 175, 183, 196, 198, 207 Therapeutics, 50, 51, 52, 60, 73, 85, 89, 117, 128, 187, 207 Thermoregulation, 117, 207 Thiothixene, 116, 207 Threonine, 203, 207 Threshold, 67, 173, 178, 207 Thrombin, 173, 194, 197, 207 Thrombomodulin, 197, 207 Thrombosis, 197, 205, 207 Thromboxanes, 156, 207 Thyroid, 122, 182, 207, 209 Tiapride, 61, 116, 207 Time Perception, 22, 207 Tolerance, 9, 26, 29, 35, 39, 76, 164, 175, 177, 207 Tone, 14, 166, 176, 179, 208 Tonic, 79, 164, 166, 208 Tonus, 208 Topical, 173, 178, 208 Torsades de Pointes, 75, 208 Torticollis, 58, 208 Toxic, iv, 45, 121, 157, 163, 185, 189, 190, 208 Toxicity, 8, 170, 194, 208, 211 Toxicology, 20, 75, 97, 136, 208 Toxin, 207, 208 Tracer, 33, 208 Trachea, 207, 208 Transdermal, 90, 101, 208 Transduction, 10, 177, 181, 208 Transfection, 159, 208 Translation, 153, 172, 208 Translational, 34, 208 Translocation, 172, 208 Transmitter, 40, 151, 157, 170, 182, 185, 190, 206, 208 Trauma, 158, 168, 188, 207, 208 Tremor, 13, 21, 185, 192, 209 Trichotillomania, 55, 209 Tricuspid Atresia, 166, 209 Tricyclic, 153, 164, 179, 185, 209 Trigeminal, 173, 209 Trigger zone, 156, 209 Triglyceride, 92, 178, 209 Troglitazone, 122, 209 Trophic, 42, 209 Tryptophan, 41, 106, 203, 209 Tubercle, 190, 209
Tuberculosis, 182, 202, 209 Tuberculostatic, 182, 209 Type 2 diabetes, 9, 209 Tyrosine, 7, 76, 170, 209 U Unconditioned, 8, 209 Unconscious, 154, 209 Urethra, 209 Urinary, 90, 163, 180, 202, 209 Urine, 75, 159, 180, 182, 209 Urodynamic, 67, 209 Uterus, 162, 167, 168, 189, 196, 209 Uveitis, 156, 209 V Vacuoles, 35, 191, 210 Valproic Acid, 58, 210 Vascular, 122, 153, 160, 169, 176, 180, 194, 209, 210 Vascular Resistance, 153, 210 Vasodilator, 160, 170, 177, 192, 210 Vector, 8, 208, 210 Vegetative, 43, 210 Vein, 181, 190, 195, 210 Venlafaxine, 90, 210 Venous, 195, 197, 209, 210 Venter, 210 Ventral, 8, 16, 24, 26, 32, 34, 36, 38, 47, 101, 178, 190, 210 Ventral Tegmental Area, 34, 36, 47, 210 Ventricle, 154, 157, 161, 166, 172, 177, 178, 190, 206, 207, 209, 210 Ventricular, 75, 91, 153, 166, 208, 209, 210 Ventricular fibrillation, 208, 210 Vesicular, 47, 210 Veterinary Medicine, 135, 210 Vinblastine, 106, 210 Vinca Alkaloids, 210 Vinyl Chloride, 122, 210 Viral, 208, 211 Virulence, 157, 208, 211 Virus, 158, 172, 194, 208, 211 Viscera, 204, 211 Visceral, 175, 183, 211 Visual field, 187, 211 Vitro, 7, 74, 96, 211 Vivo, 33, 211 Voltage-gated, 45, 211 W Wakefulness, 168, 211 White blood cell, 155, 183, 184, 194, 211 Windpipe, 207, 211 Withdrawal, 13, 38, 53, 92, 102, 168, 211
225
X Xenograft, 154, 211 X-ray, 9, 182, 190, 199, 200, 204, 211 X-ray therapy, 182, 211
Y Yeasts, 174, 193, 211 Z Zymogen, 197, 211
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