Desipramine - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

DESIPRAMINE 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., 1960Desipramine: 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: 0-497-00351-1 1. Desipramine-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 desipramine. 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 DESIPRAMINE............................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Desipramine .................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 25 The National Library of Medicine: PubMed ................................................................................ 25 CHAPTER 2. NUTRITION AND DESIPRAMINE .................................................................................. 71 Overview...................................................................................................................................... 71 Finding Nutrition Studies on Desipramine................................................................................. 71 Federal Resources on Nutrition ................................................................................................... 73 Additional Web Resources ........................................................................................................... 74 CHAPTER 3. ALTERNATIVE MEDICINE AND DESIPRAMINE............................................................ 75 Overview...................................................................................................................................... 75 National Center for Complementary and Alternative Medicine.................................................. 75 Additional Web Resources ........................................................................................................... 82 General References ....................................................................................................................... 83 CHAPTER 4. PATENTS ON DESIPRAMINE ........................................................................................ 85 Overview...................................................................................................................................... 85 Patents on Desipramine............................................................................................................... 85 Patent Applications on Desipramine ........................................................................................... 87 Keeping Current .......................................................................................................................... 88 CHAPTER 5. BOOKS ON DESIPRAMINE ............................................................................................ 89 Overview...................................................................................................................................... 89 Chapters on Desipramine............................................................................................................. 89 CHAPTER 6. PERIODICALS AND NEWS ON DESIPRAMINE .............................................................. 91 Overview...................................................................................................................................... 91 News Services and Press Releases................................................................................................ 91 Newsletter Articles ...................................................................................................................... 92 Academic Periodicals covering Desipramine ............................................................................... 93 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 95 Overview...................................................................................................................................... 95 U.S. Pharmacopeia....................................................................................................................... 95 Commercial Databases ................................................................................................................. 96 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 99 Overview...................................................................................................................................... 99 NIH Guidelines............................................................................................................................ 99 NIH Databases........................................................................................................................... 101 Other Commercial Databases..................................................................................................... 103 APPENDIX B. PATIENT RESOURCES ............................................................................................... 105 Overview.................................................................................................................................... 105 Patient Guideline Sources.......................................................................................................... 105 Finding Associations.................................................................................................................. 107 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 109 Overview.................................................................................................................................... 109 Preparation................................................................................................................................. 109 Finding a Local Medical Library................................................................................................ 109 Medical Libraries in the U.S. and Canada ................................................................................. 109 ONLINE GLOSSARIES................................................................................................................ 115 Online Dictionary Directories ................................................................................................... 117

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DESIPRAMINE DICTIONARY .................................................................................................. 119 INDEX .............................................................................................................................................. 177

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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 desipramine 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 desipramine, 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 desipramine, 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 desipramine. 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 desipramine, 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 desipramine. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON DESIPRAMINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on desipramine.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and desipramine, 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 “desipramine” (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: •

Pharmacological Treatment of Painful Diabetic Neuropathy Source: Clinical Diabetes. 18(3): 116-118. 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reviews studies on the effectiveness of various drugs in managing diabetic neuropathy. Control of pain is a major goal for most patients and their physicians in managing diabetic neuropathy. Studies have demonstrated the effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and sulindac; tricyclic antidepressants such as amitriptyline, imipramine, nortriptyline, and desipramine; serotonin reuptake inhibitors such as paroxetine and fluoxetine; and anticonvulsants such as gabapentin and carbamazepine. Although NSAIDs can offer

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pain relief, especially in patients with musculoskeletal or joint abnormalities secondary to long term neuropathy, the tricyclic antidepressants remain the most commonly used drugs in the treatment of painful neuropathy. In addition, several other oral agents including the anti-arrythmic agent mexiletine, tramadol, and topical capsaicin cream have been found to be effective in relieving pain associated with diabetic neuropathy. Other nonsystemic pain control treatments that have been studied include transcutaneous electrical nerve stimulation units and acupuncture. 28 references.

Federally Funded Research on Desipramine The U.S. Government supports a variety of research studies relating to desipramine. 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 desipramine. 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 desipramine. The following is typical of the type of information found when searching the CRISP database for desipramine: •

Project Title: ADRENERGIC DEVELOPMENT

RECEPTORS

DURING

PERIADOLESCENT

Principal Investigator & Institution: Bylund, David B.; Professor and Chair; Pharmacology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): The up-regulation or down-regulation of neurotransmitter receptors has become one of the major, proposed mechanisms for a variety of therapeutic drugs. Drug-induced regulation of central catecholamine receptors has been extensively studied in adults, but little is known about their regulation in young animals. It is particularly important to understand the nature of drug-induced regulation of adrenergic receptors in young animals for two reasons. First, adrenergic agents are used clinically in children and adolescents. Our preliminary data show that the effects of adrenergic agents on the young adrenergic system are qualitatively different from their effects on the adult. Second, because the adrenergic system is late developing, and is still changing during periadolescent development, perturbations in this system are more likely to have greater, qualitatively different, and longer-lasting effects than on a mature system. The central hypothesis of the proposed studies is that CNS alpha-2 and beta adrenergic receptors are differentially regulated in periadolescent as compared to adult rats, as reflected by responses to two drugs that effect the noradrenergic and serotonin systems (the selective re-uptake inhibitors 2

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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desipramine and fluvoxamine). The first specific hypothesis, that central adrenergic receptors will be up-regulated in periadolescent animals rather than down-regulated as observed in adult animals, will be tested using quantitative autoradiography to determine alpha-2 and beta adrenergic receptor density. The second hypothesis, that the functional coupling between the adrenergic receptors and their G proteins will be increased in the young animals as compared to adults, will be tested using cyclic AMP accumulation and GTPyS binding assays. The third hypothesis, that the functional responses to agonist stimulation will be increased in periadolescent animals as consequences of these alterations in regulation and coupling, will be studied using regulation of immediate early gene expression and agonist induced-hypothermia. These studies in rats will help provide the necessary foundation for understanding the regulation of the adrenergic receptor systems in young animals leading to an eventual understanding of the effects of chronic drug treatment in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AIRWAY-CENTRAL NERVOUS SYSTEM CONTROL Principal Investigator & Institution: Haxhiu, Musa A.; Physiology and Biophysics; Howard University Washington, Dc 20059 Timing: Fiscal Year 2004; Project Start 01-JAN-1995; Project End 31-MAR-2009 Summary: (provided by applicant): Chronic airway diseases such as bronchial asthma and chronic obstructive bronchitis share the salient features of inflammation, hyperresponsiveness to various inhalants, and airway narrowing. Although these two conditions result in enormous morbidity and social cost, the central nervous system mechanisms involved in airway hyperreactivity remain poorly understood. In the prior funding cycle of this proposal we have characterized the primary neurochemical(s) and receptor subtypes involved in transmission of excitatory inputs from the respiratory tract to the nucleus tractus solitarius (NTS) neurons; from these second order sensory cells to airway-related vagal preganglionic motor neurons (AVPNs); and from AVPNs back down to the airways. As a natural continuation of this work, we now focus on inhibitory pathways that regulate cholinergic drive to the airways. Neuroanatomical studies will define the normal neural circuitry between inhibitory GABAergic, catecholaminergic, or serotonergic cell groups and AVPNs. In these studies, retrograde tracing will be used to define AVPNs projecting to the trachea. Dual or triple labeling immunocytochemistry will be used to simultaneously locate neurotransmitters, their receptors, and AVPNs. Tissues will be examined using light microscopy, confocal microscopy, and electron microscopy. Protein levels will be measured by Western blotting. In physiological studies, we will microinject uptake inhibitors, specific agonists, or antagonists into the rostral nucleus ambiguus (rNA, where AVPNs are abundant), to define the functional roles of specific inhibitory neurotransmitters and their receptors on basal and reflex-induced changes in tracheal tone and airway resistance. Subsequently, we will test the hypothesis that repeated exposure to allergens in sensitized animals induces morphological and physiological changes in central inhibitory influences, resulting in a shift from inhibitory to excitatory transmission. These changes lead to a hyperexcitable state of AVPNs and to airway hyperreactivity. The results of these studies will provide necessary knowledge in the neural control of the airways and will support the development of novel pharmaceutical strategies which target the central nervous system for the treatment of airway disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOLOGICAL ASPECTS OF DEPRESSION & ANTIDEPRESSANT DRUGS Principal Investigator & Institution: Frazer, Alan; Professor and Department Chairman; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002 Summary: This protocol seeks to determine whether there are specific behavioral changes or a clinically detectable specific pattern of behavioral improvement that occurs within the first week of treatment for major depression. It will also evaluate whether such improvement is due to the drug used in treatment (desipramine or fluoxetine), or rather to the process of recovery, regardless of the treatment modality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTRAL BETA ADRENERGIC RECEPTORS Principal Investigator & Institution: O'donnell, James M.; Professor; Pharmacology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2004; Project Start 01-AUG-1990; Project End 30-NOV-2008 Summary: (provided by applicant): The goals of this proposal are to determine: a) the role of beta adrenergic receptors in hippocampal subregions in mediating antidepressant activity and the behavioral effects of noradrenergic antidepressants; and b) the relationship between changes in noradrenergic neurotransmission and the persistent behavioral effects that result from repeated treatment with noradrenergic antidepressants. To address these goals, four lines of investigation are proposed. First, it will be determined whether stimulation of beta-adrenergic receptors in subregions of the hippocampus produces antidepressant-like effects on behavior. This will be accomplished by determining the effects on DRL and forced-swim behavior of infusion of beta-adrenergic agonists and antagonists into subregions of the hippocampus (CA 1, CA2/CA3, dentate gyrus). Second, it will be determined whether beta-adrenergic receptors in subregions of the hippocampus mediate the behavioral effects of noradrenergic antidepressants. This will be accomplished by determining the ability of site-specific infusion of beta-adrenergic antagonists to block the effects of desipramine and reboxetine on DRL and forced swim behavior. Third, it will be determined whether the persistent behavioral effect on forced-swim behavior that occurs with repeated antidepressant treatment results from regulation of the norepinephrine transporter. This will be accomplished by comparing the dose-response and time-course of the behavioral effects with those for the regulation of the norepinephrine transporter produced by repeated treatment with desipramine or reboxetine. Fourth, it will be determined whether regulation of the norepinephrine transporter by repeated antidepressant treatment results in enhanced noradrenergic neurotransmission. This will be accomplished by comparing the dose-response and time-course of antidepressantinduced regulation of the norepinephrine transporter with those for increases in extracellular norepinephrine concentrations, measured using in vivo microdialysis. Completion of the proposed experiments will demonstrate the role that hippocampal beta-adrenergic receptors play in the mediation of antidepressant activity, particularly for those drugs thought to act via interactions with noradrenergic neurons. In addition, the manner by which adaptive changes in noradrenergic neurotransmission contribute to the development of persistent antidepressant effects will be elucidated. Overall, this work will provide new information relevant to the understanding of the pathophysiology and pharmacotherapy of depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COCAINE MECHANISMS

&

MATERNAL

AGGRESSION--OXYTOCINERGIC

Principal Investigator & Institution: Johns, Josephine M.; Associate Professor; Psychiatry; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (applicant's abstract): Cocaine abuse by human mothers is correlated with a high incidence of child neglect and abuse. Gestational cocaine (COC) treatment has been shown to increase aggression towards an intruder (maternal aggression) and reduce the levels of oxytocin (OXY) in the amygdala of rats on postpartum days (PPD) 6-10. Blocking OXY receptors in the central amygdala results in an increase in aggression

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parallel to that seen following COC treatment. COC likely decreases OXY in the amygdala and increases maternal aggression through its reuptake inhibition of dopamine (DA), serotonin (5-HT) and norepinephrine (NE). These studies are designed to elucidate the specific mechanisms through which COC may work to alter OXY and maternal aggression in rats. Specific Aim 1 will determine if gestational treatment with a combination treatment of selective DA and 5-HT uptake inhibitor will increase maternal aggression as does COC. To test this hypothesis, groups of rat dams will be treated gestationally (days 1-20) with COC, control vehicle buffer (VCB), selective DA, 5-HT, or NE reuptake inhibitors or combinations of selective inhibitors. Dams will be tested for maternal aggression on PPD 6. Specific Aim 2 will determine if gestational treatment with a combination of a selective DA and 5-HT uptake inhibitor will alter OXY dynamics as does COC. To test this hypothesis, groups of rat dams will be treated gestationally (days 1-20) with vehicle buffer (VCB), COC, selective DA, 5-HT, or NE reuptake inhibitors or combinations of the selective inhibitors and sacrificed on PPD 6. OXY levels and receptor binding will be measured by radioimmunoassay, in situ hybridization and autoradiography in the amygdala, medial preoptic area and paraventricular nucleus of the hypothalamus, all of which have been implicated in OXY regulation of maternal aggression. Specific Aim 3 will determine if gestational COC treatment reduces OXY synthesis in the medial preoptic area and paraventricular nucleus and oxytocin receptor (OTR) synthesis in the amygdala, medial preoptic area and paraventricular nucleus. To test this hypothesis, rat dams will be treated gestationally with VCB or COC, and these brain regions removed for in situ hybridization and autoradiography for assessment of OXY and OTR messenger ribonucleic acid on PPD 6. Specific Aim 4 will determine if prenatal exposure to COC and being raised by a COC treated mother as compared to being raised by mothers treated with control vehicle increases maternal aggression displayed by female offspring and decreases OXY in the amygdala of the offspring as adults. To test this hypothesis, female offspring of dams gestationally treated with COC or control vehicle buffer (2 groups, buffer with no pair feeding and buffer with pair feeding), will be raised by their natural dams or foster dams that are vehicle-treated (pair-fed and non-pair-fed) or COC and then bred and tested for maternal aggression in the presence of their own litters on PPD 6. OXY levels in the amygdala will be assessed following the behavioral testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMORBID DEPENDENCE

DISORDERS

IN

TREATMENT

OF

OPIATE

Principal Investigator & Institution: Gonzalez-Haddad, Gerardo; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Provided by Applicant) This application is to study comorbid disorders that affect the treatment of opiate dependence. The specific aims of the proposed program of research are as follows: Study 1 will examine comorbid depression as a predictive factor in treatment with desipramine and contingency management of cocaine abusing opiate dependent subjects maintained on buprenorphine by secondary data analysis of a completed randomized clinical trial. Study 2 will evaluate the efficacy of sertraline in the treatment of cocaine dependent patients with comorbid depression in a recently started double-blind randomized clinical trial. Study 3 will determine changes of health care cost after treatment of opiate dependence in the Veterans Affairs health delivery system using existing administrative databases. It will determine whether confounding factors, especially comorbid depression and cocaine dependence, may affect changes in costs.

Studies

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The overall aim of the proposal is to provide me with a supervised patient oriented research and educational experience that will enable me to become an independent investigator in substance abuse. My specific career development goals are to: (1) Acquire in-depth knowledge of the neuropharmacology of cocaine and opiate dependence, and of substance induced mood disorders. (2) Develop expertise in clinical research and management of cocaine and opiate dependence, and current pharmacotherapies. (3) Develop skills in Mental Health Service research related to substance abuse. The proposed career development plan utilizes the collaboration of Thomas Kosten, MD in developing expertise executing randomized clinical trials, Robert Rosenheck, MD in developing skills in mental health services research and Kevin Sevarino, MD, PhD in clinical management of opiate dependence. The educational experience includes a four year period of formal coursework at the Interdepartmental Neuroscience Program at the Yale School of Medicine and at the Yale School of Epidemiology and Public Health. This K23 research career award will enable me to start an academic career focusing on research in cocaine and opiate dependence and to develop a bridge between clinical trials and services research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMORBIDITY IN COCAINE AND OPIOID PHARMACOTHERAPY Principal Investigator & Institution: Kosten, Thomas R.; Professor of Psychiatry; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract) This application requests a Research Scientist Award to enable the candidate to pursue full time research and research training aimed at improving the pharmacotherapy of cocaine and opioid dependence. During the award period, the applicant will conduct pharmacotherapy trials of two types: a) combinations of novel pharmacotherapies with behavioral interventions targeted at cocaine dependent patients with comorbidities such as depression and opioid dependence, b) treatments for cocaine associated cerebral perfusion defects assessed using SPECT neuroimaging. The Research Plan uses behavioral contingencies to move forward our 10 years of work showing the efficacy of desipramine (DMI) and its combination with buprenorphine (BUP) for reducing cocaine abuse. The plan provides a detailed description of our 24 week, randomized placebo-controlled, double blind clinical trial using DMI in combination with contingency management for 160 patients who are maintained on buprenorphine for comorbid opioid and cocaine dependence. The contingency group will get a voucher worth a set monetary value that increases for consecutively drug-free urines (weeks 1-19) or a voucher with a fixed value under an increasing ratio of number of consecutive drug free urines per voucher (weeks 13-24). Subjects not in the contingency group get monetary vouchers independent of their illicit cocaine use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEPRESSION AND IMMUNITY: BEHAVIORAL AND CNS MECHANISMS Principal Investigator & Institution: Friedman, Elliot M.; Psychology; Williams College Williamstown, Ma 01267 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): Most investigators hypothesize that immunological abnormalities that have been identified in depressed individuals are secondary to

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alterations in brain function, particularly in regions and systems that are implicated in the regulation of immune function. Nonetheless, this hypothesis has not been broadly tested despite evidence that immune function is normalized by antidepressant treatment in clinical populations. The proposed research will use the Flinders Sensitive Line (FSL) genetic rat model of depression to test the hypothesis that alterations in brain monoaminergic systems contribute to depression-related abnormalities of immune function. This project builds on exciting recent data showing markedly reduced in vivo type 1 immune responses in FSL rats. Two specific aims comprise the proposed research. The first stems from previous work showing that chronic antidepressant treatment with tricyclic or serotonin-specific antidepressants normalizes behavioral and neurochemical abnormalities in the FSL rats. In the proposed studies, FSL and control rats will receive chronic treatment with the antidepressants desipramine and sertraline. These treatments are expected to normalize behavioral and immunological abnormalities in the FSL animals. The second aim will test the hypothesis that chronic intracerebroventricular infusion of norepinephrine or serotonin, the pharmacological targets of desipramine and sertraline, respectively, will normalize behavioral and immunological differences between the FSL and FRL strains. These experiments will simultaneously evaluate (a) the site of action for antidepressant effects on behavior and hypothesized effects on immune function (i.e. central or peripheral), (b) the extent to which a specific monoaminergic system may play a greater role in regulating type 1 immune responses, and (c) the immunomodulatory effects of chronic elevations in brain monoamines. Collectively, these studies build on exciting new data, and they are designed as initial steps in the process of describing a seamless chain of influence originating in the brain and culminating in altered function of specific immunological cells. Because the FSL rat has already been established as a valid model for depression, the data generated from these studies promise to illuminate the integrated biological processes that produce increased vulnerability to physical illness in the clinically depressed Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION

DEPRESSION,

EPINEPHRINE,

SEROTONIN,

&

PLATELET

Principal Investigator & Institution: Musselman, Dominique L.; Assistant Professor; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 04-FEB-2002; Project End 31-JAN-2006 Summary: Several studies have shown that major depression and associated symptoms, such as hopelessness, are a major independent risk factor in development of ischemic heart disease (IHD), and for death after an index myocardial infarction. Not only do platelets play a central role in hemostasis, atherosclerosis, and acute coronary syndromes, but patients with major depression exhibit increased numbers of the functional platelet GPIIb/IIIa receptor, the receptor for fibrinogen and other ligands, and the final common pathway by which platelet aggregation and adhesion occurs. The overall goal is to determine in patients with major depression, the specific molecular pathways, and relative contributions of these pathways, whereby the platelet GPIIb/IIIa receptor is converted from a low- affinity to high-affinity conformation. To accomplish this goal, we will scrutinize in men with unipolar, recurrent, major depression, not only depression severity and platelet GPIIb/IIIa receptors, but characterize platelet autocrine "feed forward" pathways via: platelet serotonin (5HT) and 5HT2 receptors, platelet adenosine triphosphate (ATP) release, and urinary excretion of 11-dehydrothromboxane

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beta2: (1) under controlled basal conditions, (2) after the Trier Social Stress Test (a sustained mental stressor which will stimulate platelet function via peripheral release of the platelet agonist epinephrine). Moreover we will determine the molecular mechanisms whereby antidepressant treatment reduces numbers of high-affinity GPIIb/IIIa receptors, using randomized, double-blind, treatment with paroxetine (a selective 5HT reuptake inhibitor) in comparison to desipramine (a noradrenergic tricyclic). State-of- the-art techniques will be used, including fluorescence activated flow cytometry (FAFC), platelet calcium mobilization, and evaluation of in vitro antidepressant direct "drug effects" of upon platelet function. Novel information will be gleaned regarding not only the biological basis for the increased vulnerability of depressed patients to IHD, but also potential thrombovascular targets whereby psychopharmacologic interventions might reduce the future risk of heart attack and sudden death in patients with major depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEPRESSION/METABOLIC SYNDROME IN MEXICAN-AMERICAN WOMEN. Principal Investigator & Institution: Licinio, Julio; Professor of Psychiatry and Medicine/En; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This grant application has been developed to test the hypothesis that insulin resistance and hyperglycemic trends parallel plasma cortisol levels in major depressive disorder (MDD). We will also test the more focused hypothesis that treatment of depressive symptoms ameliorates state of insulin resistance. We will approach these hypotheses by studying depressed MexicanAmerican women from a rigorously characterized cohort of patients who have been recruited into our NIGMS-funded project in pharmacogenomics of antidepressant treatment response (GM61394). This application builds on the enormous resource provided by that prospective study, which provides the opportunity to recruit and treat these individuals. That project is a carefully designed, prospective clinical phase IIA randomized longitudinal study, using two pharmacological agents (desipramine and fluoxetine) with demonstrated efficacy in the treatment of MDD in the MexicanAmerican population. Clinical status is assessed with clinical interview and ratings such as the Hamilton Ratings Scale for Depression, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. These instruments have been extensively validated in Spanish. That project is a treatment study with single- and double-masking, with random assignment of treatment, and with outcomes assessed with clinical measures. All subjects will undergo comprehensive intake assessments, and will then have follow-up assessments. Treatment will be provided according to our approved protocol. We propose to conduct detailed endocrine, nutritional, and metabolic studies in normalweight Mexican-American women, who are otherwise medically healthy and who will be extensively characterized for our pharmacogenomic study. This proposal will permit the ascertainment of degree of insulin resistance in MDD through the assessment of endocrine (HPA axis and leptin measurements), nutritional, body composition, and metabolic function (insulin sensitivity will be assessed by oral glucose tolerance test, glucose clamp and arginine stimulation test) before and after treatment. Treatment outcome data will be correlated with endocrine and metabolic endpoints. Several lines of evidence suggest diabetes mellitus is often associated with depression and that depression increases the risk of developing diabetes. This work will address this

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important area by the study of an population group who is markedly under represented in patient-oriented investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DO CONSISTENTLY?

ANTIDEPRESSANTS

AFFECT

LOCUS

COERULEUS

Principal Investigator & Institution: Weiss, Jay M.; Professor; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant): The research proposed here will assess how electrophysiological activity of neurons of the major noradrenergic cell-body group of the brain, the locus coeruleus (LC), is altered by effective antidepressant (AD) treatment. The primary impetus for this research is evidence from both preclinical and clinical research that raises the possibility that all presently-known effective AID treatments reduce activity of LC neurons. Recently, we reported that, in experimental animals (rats), both spontaneous firing rate and sensory-evoked "burst" firing of LC neurons were decreased following all AD treatments examined, including several types of drug therapy and also electroeonvulsive shock (ECS). This change resulted from chronic drug admires" tration (i.e., for 14 and 30 days by subcutaneous minipump) of five AD drugs (two tricyclics, two SSRIs, and an MAO inhibitor) and a series of 5 ECSs. These findings, together with previously accumulated results, form a sizable body of data indicating that AD treatments decrease LC activity. The present study will continue to measure both spontaneous and sensory-evoked LC electrophysiological activity, extending the number of AD treatments surveyed and addressing important remaining issues. First, effects produced by chronic administration of several AD and non-AD drugs that we have not examined previously as well as by promising new therapies (i.e., a CRH antagonist, NK-1 receptor blocker, and rTMS) will be determined. Particular attention is directed to two AD drugs (mianserin and mirtazapine) that block a2pha adrenergic receptors and thus acutely increase (rather than decrease) LC activity; however, data from chronic administration of these drugs are contradictory. By the conclusion of this experiment, our fmdmgs plus those of others will have determined effects on LC activity of a relatively comprehensive list of known effective AD treatments and also will have begun to assess whether reduced LC activity is specific to ADs (by testing nonAD drugs). Second, because mount of drug (i.e. blood level of drug) may be quite important in determining response, changes in LC activity resulting from different doses of desipramme (a tricyclic), sertraline (an SSRI), and the two drugs that block a2 receptors (mirtazapine and mianserin) will be assessed, with blood levels also measured. Finally, effects on LC activity will be determined for these four drugs when the rats take drug orally in a manner analogous to taking a pill. While minipumps provide reliable and consistent drug delivery for the rat, humans usually take drug in pill form, which introduces drug orally in a bolus. Effects might differ if drug is given in this way and blood levels vary somewhat across the day. Consequently, a method has been developed to induce rats to voluntarily take drug orally in a manner similar to a pill, and effects of this will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAERGIC & GLUTAMATERGIC AGENTS--COCAINE USE IN METHADONE MAINTENANCE Principal Investigator & Institution: George, Tony P.; Associate Professor of Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047

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Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2003 Summary: This section of this Medications Development Unit (MDU) outlines phase ll screening studies for armacotherapy of cocaine use in methadone- maintained subjects with agents that act through GABAergic or lutamatergic mechanisms. These studies would be carried out in two parts, with GABAergic agents being tested in Years l-2, and glutamatergic agents in Years 3-5. Our group has a long history of completing pharmacotherapy trials in cocaine-using methadone subjects, and examples have included desipramine, mazindol, amantadine, bromocriptine and bupropion. Preclinical evidence indicates that GABA and glutamate systems can modulate dopamine reward pathways which are thought to underlie the addictive properties of cocaine, and agents which modulate GABA and glutamate systems can reduce the reinforcing properties of cocaine in animal models. The GABAergic agents chosen for these pilot studies are: l) the GABAB agonist baclofen; and 2) the selective GABA reuptake inhibitor tiagabine. The glutamatergic agents chosen for phase I studies are: l) the NMDA receptor antagonist acamprosate and 2) the pre~synaptic glutamate release inhibitor lamotrigine. A total of 60 subjects will be recruited into each study for a total of 120 subjects over the entire five year period. Subjects will be randomized to one of five cells: placebo or two different doses of either baclofen or tiagabine (Study 1) or acamprosate or lamotrigine (Study 2) for a total of 8 or 12 weeks of active treatment for GABAergic and glutamatergic agents respectively. At the end of the active trials, medications would be tapered over a two week period. Primary outcomes will be selfreported cocaine use, three times weekly urine toxicology for the cocaine metabolite benzoylecgonine and treatment retention. It is hoped that we will demonstrate the efficacy and safety one or more of these agents for cocaine use in opiate-maintained subjects, and if encouraging results are obtained, phase ll controlled studies would be planned with promising candidates identified from these phase ll screening trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION PROFILE OF ANTIDEPRESSANTS Principal Investigator & Institution: Duman, Ronald S.; Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Depression is characterize behaviorally by depressed mood, inability to experience pleasure, withdrawal of interest, and feelings of worthlessness which can often result in a debilitating quality of life, as well as suicide in many cases. Despite the significant advances that have been made in neurobiology and neuropharmacology of antidepressants, the molecular mechanisms underlying the actions antidepressant treatment have not been identified. Although the acute action of most antidepressants occurs via inhibition of the reuptake or breakdown 5-HT and NE, increased synaptic levels of these monoamines alone cannot account for the therapeutic action of antidepressants. Recent studies have shown that chronic antidepressant treatment (ADT) alters gene expression, especially components of cAMP signal transduction cascade. The delay in the therapeutic effects of ADT coincides with changes in gene expression in intracellular pathways, and it is thought that these changes mediate the therapeutic effects of antidepressants. It is known that stress and antidepressants have opposing actions on neuronal growth and vulnerability, in part due to the opposing effects on expression of neurotrophic factors. We hypothesize that stress and antidepressant administration have reciprocal changes in gene expression profiles. The aim of this R21 Exploratory Grant is to characterize the gene expression profiles to different classes of ADT, including 5-HT and norepinephrine selective

14

Desipramine

reuptake inhibitors and ECS, and compare these profiles with changes observed with stress. It is however necessary to distinguish between acute and chronic alterations in response to ADT as only chronic ADT has been shown to possess therapeutic effects. This can be accomplished by comparing expression profiles by microarray analysis at various time points after and ADT. Gene expression changes will be characterized in the hippocampus and dentate gyrus of rat brain. This will increase our understanding of the mechanisms underlying the actions of antidepressant treatment and could lead to novel therapeutic targets. The results from these studies should lead to an ROl proposal aimed at extending these findings. Briefly, further studies would involve modulating the expression of genes identified by viral-mediated expression of genes in discrete brain regions and generation of transgenic mice, for study in behavioral models of stress and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISOTOPE DILUTION GAS CHROMAT MASS SPECT MEASURE OF TRICYCLIC ANTIDEPRESSANT Principal Investigator & Institution: Way, Barbara; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002 Summary: Stable isotope dilution gas chromatographic-mass spectrometric (GC-MS) measurement of tricyclic antidepressants (TCA) is a useful alternative to high performance liquid chromatographic (HPLC) methods when interfering substances prevent accurate quantitation by HPLC. For satisfactory GC-MS analysis, secondary amine TCA must be derivatized. Commonly employed trifluoroacetyl and heptafluorobutyryl derivatives are relatively unstable and cause rapid deterioration of capillary gas chromatography (GC) columns. We have therefore examined 4carbethoxyhexafluorobutyryl chloride (CHFB-Cl) as an alternate derivatizing agent and have developed a stable isotope dilution GC-MS method employing ring-labeled [2H4]desipramine and [2H4]-imipramine internal standards which permits measurement of desipramine, nortriptyline, imipramine, and amitriptyline in plasma samples containing one or all of these analytes. The GC-MS assay is linear for each analyte from the lower limit of quantit ation (25 ng/mL) up to 1500 ng/mL and correlates well with HPLC measurements. The GC-MS analytic coefficient of variation was 9.7 1 1.3% for all analytes considered together. Although interferences are observed in the HPLC assay, thioridazine, perphenazine, cyclobenzaprine, or norcyclobenzaprine do not interfere with GC-MS measurements of the TCA examined here. The stability of the CHFB derivative of secondary amine TCA was found to be superior to that of the trifluoroacetyl derivatives of these compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MECHANISM OF DEPRESSIVE BEHAVIOR IN WISTAR-KYOTO RATS Principal Investigator & Institution: Tejani-Butt, Shanaz M.; Pharmaceutical Sciences; University of the Sciences Philadelphia in Philadelphia Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-JUN-2001; Project End 31-MAY-2005 Summary: (provided by applicant): The Wistar-Kyoto (WKY) rat has been proposed as a useful animal model in which to study the connection between stress responsiveness and vulnerability to depressive behavior. Physiologically, the WKY rat shows greater susceptibility to stress-induced gastric ulcers than other strains. Endocrine studies

Studies

15

report that WKY rats have high levels of stress-induced adrenocorticotropin and low levels of corticotropin releasing hormone, suggesting a defective feedback in the hypothalamic-pituitary-adrenal (HPA) axis. Our research has revealed significant differences in central norepinephrine (NE) and serotonin (5-HT) sites in WKY rats when compared to Sprague-Dawley rats. Treatment with desipramine (a NE uptake blocker), but not paroxetine (a 5-HT uptake blocker), decreased immobility time in the Porsolt forced swim test, and reduced ulcer incidence, implicating the NE system in the mediation of depressive behavior in WKY rats. This grant is aimed at further substantiating the value of the WKY model, and is designed to determine the mechanisms that mediate the disease condition. Differential sensitivity to antidepressants with distinct pharmacological actions may provide useful information regarding the underlying substrates that contribute to a selective response in the WKY rat. Thus the central objective is to ascertain whether antidepressants that target specific neurotransmitter sites in the brain, will alleviate depressive behavior and attenuate the animal's responsiveness to stress. This behavioral response is expected to decrease ulcer susceptibility, modify feedback in the HPA axis, and reverse the characteristic NE and 5HT receptor alterations in the WKY rat. A positive answer to this objective will provide significant information regarding the mechanisms that underlie depressive behavior and ulcer susceptibility in this vulnerable rat strain. The information gained from this study could provide a better understanding of why a clinical response is observed in some populations of depressed patients, while a resistance in treatment response is seen in others. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF SYMPATHETIC NEURON SPECIFICATION Principal Investigator & Institution: Sieber-Blum, Maya F.; Professor; Cell Biol, Neurobiol/Anatomy; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Adapted from applicant's abstract): The long-term goal of the proposed work is to elucidate the mechanisms that underlie cornmitment of the pluripotent neural crest stem cell to the sympathetic neuron cell lineage. Whereas stem cells express the nonselective neurotrophin receptor, p75NTR and the neurotrophin-3 (NT-3)-selective receptor, TrkC, sympathetic neurons express the norepinephrine transporter (NET), tyrosine hydroxylase (TH), dopamine-~-hydroxylase (DBH), the nerve growth factorselective receptor, TrkA, and p75NTR. The overall hypothesis states that neurotrophin-3 (NT-3) action and norepinephrine transport are critically involved in these developmental changes. The in vitro colony assay that has been developed in this laboratory will be used to assess and quantify the influences of NT-3, norepinephrine (NE) and NE uptake inhibitors on sympathetic neurogenesis. There are 3 specific aims. In Aim 1 it will be determined by multiplex RT-PCR, fluorescent in situ hybridization, confocal microscopy, immuno-electron microscopy, nuclear runoff assay and a TrkC knock-down strategy whether the basicfibroblast/NT-3 growth factor combination induces transcription of the NET by activating TrkC. In Aim 2 it will be determined by ratio imaging whether norepinephrine transport causes calcium influx by activating voltage-gated calcium channels. Aim 3 will start to identify, by use of antibodies against activated signaling mediators and of dominant negative and constitutively active forms of signaling mediators, the signaling pathways by which NE-mediated calcium transients regulate expression of TrkA, TH and DBH. The proposed work will fill in some of the gaps of knowledge of the causal relationship between extracellular signaling

16

Desipramine

and gene expression. A better understanding of the molecular mechanisms that control the early phases of sympathetic neurogenesis is also pertinent to function and disorders of the autonomic nervous system. Moreover, characterization of the properties of the neural crest stem cell may become a useful aid in nervous system regeneration and reconstitution of function. Finally, the fact that the tricyclic antidepressant, desipramine, and the drug of abuse, cocaine, block noradrenergic differentiation in vitro and in the embryo has important implications for mental health. Both types of drug easily cross the placenta and can cause autonomic disturbances in infants born to mothers who have been treated with the antidepressant, or who have used cocaine during pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NET - SELECTIVE LIGANDS FOR THE TREATMENT OF DEPRESSION Principal Investigator & Institution: Johnson, Kenneth M.; Professor; Acenta Discovery, Inc. Suite 300 Tucson, Az 85747 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): World-wide public health surveys point to an increased global health burden for serious psychiatric disorders, particularly depression. Indeed, by 2020 it is expected that depression may be the second most serious medical condition with respect to global disease burden. It is clear that more effective pharmacotherapies are needed in treating depressive illness. Selective ligands for the norepinephrine transporter (NET) such as desipramine are quite effective in some patient populations, but their use is often limited by side effects, particularly those thought to be mediated by their anticholinergic properties. More selective NET ligands may have considerable application in the treatment of depression. However, currently there are very few NET-selective ligands available. The studies described in this research proposal involve the synthesis and pharmacological evaluation of novel conformationally constrained tricyclic tropane analogues that are designed to be potent NET-selective inhibitors. For the best NET inhibitors identified, we will then screen them in animal models of depression. Additionally, it is reasonable that such ligands could be utilized with positron emission tomography (PET) imaging to assess changes in noradrenergic terminal fields in a variety of human conditions including depression. Thus, these ligands could be a significant addition to the clinical armamentarium available to treat and diagnose psychiatric disease. Within the context of this grant, it is our intention to follow up on our exciting preliminary findings of potent NET-selective compounds by conducting the following studies: 1. Further elaborate the biaryl and thienyl series of conformationally constrained tricyclic tropane analogues based on the SAR information already in hand; 2. Investigate certain phenylacetylene analogues that are derived from our biaryl analogues by the replacement of Ar1 with a triple bond as an aromatic ring bioisostere.; 3. Assay the inhibitory activity of all new ligands at the NET, SERT, DAT and the muscarinic receptor; 4. Scale up the synthesis of the most drug-like NET-inhibitors and study these in animal models of depression. Key words: depression, norepinephrine transporter (NET) inhibitors, conformationally constrained tricyclic tropanes, pharmacotherapy, PET imaging, chemical synthesis, behavioral testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW APPROACHES TO COCAINE ABUSE MEDICATIONS Principal Investigator & Institution: Nunes, Edward; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098

Studies

17

Timing: Fiscal Year 2002 Summary: The overall aims of this Project are to test new medications for cocaine abuse and to improve the methodology of clinical trials for evaluating candidate medications. in the current funding period a modified placebo- controlled crossover trial was designed to pilot test the efficacy of the dopamine antagonist risperidone. Currently underway is the first controlled trial of an antidepressant medication, desipramine, to focus on the subgroup of cocaine-dependent patients with depression. The specific aim of the coming funding period is to evaluate the efficacy of a promising new antidepressant agent, venlafaxine. Numerous clinical trials of antidepressant medications have been conducted, producing little evidence of efficacy in the treatment of cocaine dependence. in these trials cocaine dependence was conceptualized as a unitary syndrome, and medications were tested in unselected samples. This Project pursues an alternative model--that cocaine dependence is heterogenous with subtypes which respond to different treatment approaches. Depression is considered a promising target because it is the most common comorbid psychiatric disorder in cocainedependent samples, where it is more prevalent than in the general population and has been associated with poor outcome. Depression and cocaine dependence manifest similar neurochemical derangements. Subgroup analyses of prior antidepressant trials suggest efficacy against cocaine abuse in the depressed subgroups, and an interim analysis of our desipramine data appears promising. Venlafaxine is considered promising because it has a favorable side-effect profile, a broad spectrum of action, and rapid onset of effect. A pilot trial suggests it was rapidly effective in a series of treatment- refractory cocaine abusers. A 12-week randomized, controlled trial is proposed to test whether venlafaxine is superior to placebo in reducing depressive symptoms and cocaine use in cocaine dependent patients with current depressive disorders. Methodologic features intended to improve the efficiency of randomized controlled pharrnacotherapy trials for cocaine abuse include a placebo lead-in, concurrent manual-guided psychotherapy, and a double blind continuation phase for responders in the acute trial. This trial will yield clinically useful information on the efficacy of a promising new agent for cocaine dependence, and further inform the field on the strategy of targeting subgroups as a model for drug abuse medication development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOREPINEPHRINE TRANSPORTERS: TARGETS FOR ADHD Principal Investigator & Institution: Tarazi, Frank I.; Molecular Insight Pharmaceuticals, Inc. 160 2Nd St Cambridge, Ma 02142 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2005 Summary: (provided by applicant): Attention-deficit hyperactivity disorder (ADHD) is a complex developmental behavioral and cognitive disorder characterized by hyperactivity, inattention and impulsivity. The most widely prescribed pharmacological treatment for ADHD patients has been psychostimulants, including methylphenidate and amphetamines. Though effective in alleviating symptoms of ADHD, these medications are commonly associated with undesirable side effects, prompting the search for novel non-psychostimulant treatments for ADHD. In addition to their potent effects on the dopamine (DA) system, psychostimulants increase the release of norepinephrine (NE) more profoundly than that of DA and serotonin (5-HT), indicating that enhancing NE neurotransmission contributes to the beneficial therapeutic effects of psychostimulants. Features of clinical ADHD are commonly modeled in juvenile rats following neonatal lesioning with 6-hydroxydopamine (6-OHDA). Such rats exhibit

18

Desipramine

several characteristics resembling symptoms of ADHD including motor hyperactivity and learning deficits that can be dose-dependently antagonized by psychostimulants. A recent discovery from our laboratory is that highly selective NE transporter inhibitors (desipramine and nisoxetine) reversed the locomotor hyperactivity associated with neonatal DA lesioning in juvenile rats, suggesting that NE transporters may constitute novel targets for ADHD pharmacotherapy. This project includes further chemical, pharmacological and behavioral characterization of the role of NE transporters in the pathophysiology and treatment of ADHD. Several novel NE transporter inhibitors will be chemically synthesized using our proprietary 4-arylpiperidine pharmacophore to optimize their activity at NE transporters. This will be accomplished by modifying the 3substitutent to exploit the rich structure-activity relationships available for increased potency and/or selectivity for NE transporters. The pharmacological profile of these compounds will be characterized by determining their affinity to NE, DA, 5-HT transporters and representative NE receptors, as well as their molecular functionality at NE transporters. The behavioral effects of novel selected compounds that exhibit high affinity and selectivity at NE transporters, and block functional reuptake of synaptosomal NE will be assessed in juvenile hyperactive rats to determine their efficacy in reversing locomotor hyperactivity. Expected findings should lead to novel compounds that can be developed as much needed innovative non-stimulant treatments for ADHD and other major neuropsychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PET IMAGING--COMORBID COCAINE DEPENDENCE AND DEPRESSION Principal Investigator & Institution: Rubin, Eric; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Applicant's Abstract) Comorbidity of cocaine dependence and major depressive disorder (MDD) poses an important clinical challenge. The relatively high incidence of such comorbidity and a variety of previous investigations raise intriguing questions about neurobiological connections between these disorders. We will use positron emission tomography (PET) of human brain metabolism, before and after treatment of the comorbid disorders, as a window into such neurobiological relationships. Our team combines expertise in advanced functional brain imaging with experience in the diagnosis and treatment of comorbid MDD and cocaine dependence. Subjects for this study will be carefully screened volunteers in four samples: cocainedependent (CD) only, MDD alone, CD comorbid with MDD, and normal controls. Equal numbers of males and females will be recruited to assess gender differences. The MDD and CD+MDD groups will be treated for 12 weeks with venlafaxine, an antidepressant which our pilot data indicates is effective in the comorbid population. Specific hypotheses about the profile of cerebral metabolism in these groups will be examined as follows: 1) at baseline in all groups, 2) following treatment, when baseline and posttreatment scans will be compared to identify brain sites potentially involved in treatment effects, and 3) following treatment, when baseline scans for responders and non-responders in each treatment group will be correlated with treatment outcome to identify pre-treatment metabolic features which predict responsiveness. We will apply advanced quantitative procedures for examining global, regional, and "network" brain metabolism, and will correlate these measures with standardized measures of treatment success. This methodologic rigor will contribute to understanding the pathophysiology and treatment of patients with comorbid depression and cocaine dependence.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOGENETICS OF ANTIDEPRESSANT DRUGS Principal Investigator & Institution: Wong, Ma-Li; Professor; Psychiatry & Biobehav Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This is a revised grant application that describes a meticulous program of patient-oriented research and mentoring. The P.I. is a physicianscientist with an outstanding track record in data based, hypothesis-driven patientoriented and laboratory based investigation, and mentoring. As the Director of the UCLA GCRC Core Lab, Associate Editor of Molecular Psychiatry (Nature Publishing), and as member of the: 1) UCLA Graduate Training Program in Translational Investigation (K30); 2) UCLA Neuroscience Interdepartmental Program; 3) Neuropsychiatric Institute Research Council Group); 4) UCLA GCRC Advisory Board; 5) UCLA Mentored Clinical Pharmacology Research Scholar Program (K12) Advisory Committee the P.I. is uniquely prepared to provide clinical research training and to mentor junior clinical investigators. This award would support the PI's efforts to develop a new mentoring program both in her own area of research and in the core components of clinical research. This includes mentoring in the fundamental skills, methodology, theories, and conceptualizations necessary for the formation of wellrounded, independent, clinical researchers. The P.I. will mentor young investigators in the design of clinical research projects, hypothesis development, clinical pharmacology and pharmacogenomics, scientific writing, and the legal, ethical and regulatory issues related to clinical research. One of the unique aspects of this application is a research and mentoring plan that will address the training of minority clinical researchers and the conduction of research in ethnically identified minority populations. To address these topics, we have developed an outreach effort that consists of a process of community consultation that includes an educational series to understudied ethnic groups. The research proposal tests the hypothesis that genetic polymorphisms might determine a patient's response to antidepressants. This hypothesis will be tested by a prospective clinical phase IIA randomized longitudinal study, using two pharmacological agents (namely Desipramine and Fluoxetine) with demonstrated efficacy in the treatment of depression, in the Mexican-American ethnic population. Clinical status will be assessed with clinical interviews and ratings such as the Hamilton Ratings Scale for Depression, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. These instruments have been extensively validated in Spanish. This is a prospective outpatient treatment study with single- and double-masking, with random assignment of treatment, and with outcomes assessed with clinical measures. All subjects will undergo a comprehensive intake assessment, and will then have follow-up assessments and treatments according to our protocol. This K-24 award will make possible for the P.I. to significantly increase her time allocation for patient-oriented research and for mentoring of junior trainees and fellows in clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOLOGIC PROBES IN NEURALLY-MEDIATED SYNCOPE Principal Investigator & Institution: Biaggioni, Italo; Professor of Medicine and Pharmacology; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004

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Summary: The overall goal of these studies is to define the critical pathophysiological features of subtypes of neurally-mediated syncope, a disorder that cause substantial morbidity in young and middle-aged patients. Syncope is a common problem, accounting for as many as 3% of all emergency department visits. While attention has appropriately focused on life-threatening causes, the 30-65% of patients who are categorized as having either "reflex" or "unknown" causes suffer significant capacity as well. The underlying hypothesis of these studies, supported by recent preliminary data, is that patients with neurally- mediated syncope may be categorized by differential abnormalities of autonomic cardiovascular regulation that will predict therapeutic responses. We will address both central and peripheral autonomic mechanisms in hypothesis-driven clinical studies, and follow with a 2- year clinical trial, based on the results of these investigations. We will study patients and matched normal control subjects, assessing autonomic responses directly using recordings of muscle sympathetic nerve activity and determination of norepinephrine spillover and clearance, as well as plasma levels of circulating catecholamines and their metabolites, both at yeast and in response to sympathetic stimulation with well-characterized cortical stressors (modified Stroop and mental arithmetic with interpersonal provocation), physiological stressors (isometric handgrip and cold) and graded head-up tilt. We will also define whether peripheral vascular responses are altered. In patients with reduced sympathetic responses, we will assess alternative approaches to enhancing such responses, using alpha2 receptor antagonism with yohimbine or inhibition of the norepinephrine transporter with desimipramine. We will define the effect of sub-acute (5d) treatment with these agents on central and peripheral alpha-adrenergic responses, and determine whether a withdrawal phenomenon exists. Finally, depending on the results of these studies, we will conduct a 24 month, placebo-controlled, randomized clinical trial of these agents, assessing their efficacy in preventing syncopal episodes, their effect on cardiac rhythm, their possible central side effects, and the potential adverse effects of increased sympathetic tone on cardiac mass and chamber size with echocardiography. These studies will be directly applicable to the evaluation and treatment of patients with these incapacitating disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOLOGIC REHABILITATION OF ATTENTION DEFICITS Principal Investigator & Institution: Whyte, John; Director; Moss Rehabilitation Hospital 1200 W Tabor Rd Philadelphia, Pa 19141 Timing: Fiscal Year 2002; Project Start 10-MAY-1999; Project End 30-APR-2004 Summary: (Adapted from the Applicant's Abstract): Attention deficits are frequently reported after traumatic brain injury (TBI) and have significant consequence for the rehabilitation process as well as for subsequent education or vocational pursuits. However, controversy exists regarding the precise components of the distributed arousal and attentional system that are impaired by TBI, and the most effective treatment. Multiple neurotransmitter systems, including norepinephrine, dopamine, serotonin, and acetylcholine, are known to be affected by TBI, and uncontrolled trials of drugs which manipulate these systems are thought to be potentially beneficial. The proposed research makes use of drugs which manipulate the dopaminergic (bromocriptine) and noradrenergic (desipramine) systems, as well as those which affect both of these systems (methylphenidate), to clarify theoretical questions about the nature of attentional systems and their impairment, as well as to derive practically useful therapeutic efficacy data. Subjects with subacute or chronic TBI will be administered one of the above medications in a double-blind, placebo-controlled, cross-

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over design. Dependent variables will include a wide range of measures ranging from laboratory tasks focusing on single facets of the arousal and attention system, to ecologically valid complex measures of attention-related performance. A pilot group of 10 subjects will be tested initially to identify dependent variables likely to be sensitive to drug effects. A larger follow-up study will confirm the drug benefits in multivariate analysis. Additional analyses will assess the factor structure of the arousal and attention system and individual subject variables that predict impairment and response to treatment. The factor structure will also be compared to that obtained from a control sample. 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 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

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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: REAL-TIME NOREPINEPHRINE TRANSPORTER KINETICS Principal Investigator & Institution: Schwartz, Joel W.; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 13-MAR-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Central nervous system noradrenergic signaling modulates attention, mood, arousal, learning and memory. Specifically, norepinephrine reuptake is implicated in the pathology of major depression, posttraumatic stress disorder and attention deficit disorder. Therapeutic agents for the treatment of depression inhibit norepinephrine transporter (NET) and serotonin transporter (SERT) activities, elevating the concentration of these transmitters in the synaptic cleft. Antidepressants that inhibit NET, such as desipramine, are effective for the treatment of depression. Biogenic amine transporters are also biological targets for drugs of abuse, such as cocaine and amphetamine. The work described in this research proposal investigates substrate translocation, in which we develop novel methodology for measuring NET, SERT and dopamine transporter (DAT) activity. The fluorescent-based uptake assay described in Specific Aim I can be used as a nonisotopic method for highthroughput drug screening probing for compounds that interact with NET, SERT or DAT. The studies outlined in Specific Aim II examine the correlation between substrate and charge movement. Information garnered from these studies, can help assess the contribution of neurotransmitter transporters to synaptic transmission. The advancement in methodology enables the analysis NET activity in individual neurons, thus providing insight into endogenous NET function. These data may also provide a better understanding of therapeutic agents and drugs of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION TRANSPORTER

OF

THE

HUMAN

NOREPINEPHRINE

Principal Investigator & Institution: Ordway, Gregory A.; Associate Professor; Psychiatry and Human Behavior; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 31-AUG-2004 Summary: (from applicant's abstract): The human norepinephrine transporter (hNET) is a high affinity binding site for many psychotherapeutic compounds, including those with antidepressant efficacy (e.g. tricyclic antidepressants). The uptake of norepinephrine (NE) by the NET is the principal mechanism by which the action of NE is terminated at the noradrenergic synapse. Regulation of NET activity in the plasma membrane, therefore, represents an important candidate mechanism through which modulation of noradrenergic ransmission can occur. Despite the fact that many psychoactive compounds bind to the NET, the regulation of NET function induced by these ligands is poorly understood. Our preliminary data demonstrate that certain inhibitors (those which are antidepressants) of NET down-regulate NET function. In fact, exposure to certain NET inhibitors reduces NET function in he absence of the inhibitor for a period of time greater than the initial exposure period. The implication of this data is that occupation-induced down-regulation of NET function may contribute to the therapeutic/ pharmacological action of drugs that bind to the NET. The goals of this

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proposal are to examine the ability of NET ligands to induce NET down-regulation in in vitro and in vivo preparations, and to elucidate the molecular mechanisms responsible for ligand-induced NET down-regulation. Following continuous exposure of intact NET-expressing cells to NET ligands, studies will examine: (1) NET uptake capacity (function) in in vitro uptake assays, (2) the possibility that there is a rapid redistribution of NET from the plasma membrane surface,(3) the role of protein kinases in ligandinduced NET regulation, and (4) the turnover of NET protein and levels of NET messenger RNA. The biological relevance of NET ligand-induced regulation of NET in vitro will be established by studying NET function in brain slices following treatment of rats with NET ligands. Emphasis in in vitro and in vivo studies will be placed on the temporal aspects of regulation and recovery, because slow recovery from inhibitorinduced down-regulation may imply that antidepressant compounds do not need to be present at the NET in order to inhibit uptake. This information may have a significant impact on treatment regimens of NET inhibitors in the management of psychiatric diseases. Overall, the proposed studies will reveal the basic principles of the relationship between drug exposure and NET regulation and will provide important clues relevant to the pharmacological actions of psychoactive agents that bind to the net. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF NUCLEUS ACCUMBENS CREB IN DEPRESSION Principal Investigator & Institution: Carlezon, William A.; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: From applicant's abstract): The proposed studies are designed to examine if the transcription factor CREB (cAMP response element binding protein) in the nucleus accumbens shell (NASh) plays a role in depression. Although the NASh is involved in the hedonic (pleasurable) effects of food, sex, and addictive drugs, little is known about its involvement in mood disorders. We found previously that blockade of CREB function in the NASh increases cocaine reward in rats, whereas elevated CREB function in this region eliminates cocaine reward. Because anhedonia (a diminished ability to experience pleasure) is a hallmark symptom of depression, these data suggest that CREB (and genes regulated by CREB) in the NASh may be involved in depressive syndromes. To address this question, we have examined relationships between CREB function in the NASh and behavior in the Porsolt forced swim test (FST), a model of depression. In preliminary studies, we find that exposure to the FST causes immediate increases in phospho-CREB (P-CREB, an activated form of CREB) in the NASh. To examine the significance of this effect, we elevated CREB expression in the NASh by viral-mediated gene transfer. This treatment increases immobility in the FST (suggesting increased depression), whereas blockade of CREB function in the NASh (by overexpression of a dominant negative CREB) decreases immobility (suggesting an antidepressant effect). Together, our work suggests that CREB in the NASh is a molecular regulator of at least some symptoms of depression (anhedonia, despair). We propose to further examine the interaction of CREB (and CREB-regulated genes) in the NASh with two antidepressants (desipramine, fluoxetine) in the FST. First, we will determine if antidepressants block CREB-induced increases in immobility. Second, we will examine the time course of FSTinduced P-CREB elevations in the NASh, and determine if they are blocked by antidepressants. Third, we will determine if the FST increases expression of dynorphin, a target gene of CREB. Fourth, we will determine if blockade of the brain receptors for dynorphin (k opioid receptors) has antidepressant actions. Finally, we will use intracranial self-stimulation (ICSS) to examine if elevated CREB expression in the NASh

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produces symptoms of depression in a second behavioral assay. These studies may establish that elevated CREB expression in the NASh is a "molecular trigger" for depression, and identify novel targets for pharmacotherapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VULVAR VESTIBULITIS TRIAL: DESIPRAMINE-LIDOCAINE Principal Investigator & Institution: Foster, David; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Studies are proposed for the subtype of vulvodynia known as vulvar vestibulitis. The first major aim of this application is to conduct a randomized, placebo-controlled, double-blinded clinical trial to study the clinical efficacy of four medical regimens: topical lidocaine, oral desipramine, topical lidocaine combined with oral desipramine and placebo. The efficacy of standard treatments for vulvar vestibulitis proven by randomized, placebo-controlled, blinded clinical trials has not been assessed. The tricyclic class of antidepressants, represented by desipramine, have gained empiric acceptance for the treatment of vulvar vestibulitis, although favorable therapeutic results have been reported by only a few retrospective studies or uncontrolled clinical trials. Although the precise mechanism of action remains undefined for tricyclic antidepressants, a "central" action through the dorsal horn and brain stem has been suggested. In contrast to oral desipramine, the long-term, topical application of lidocaine may act through a "local" mechanism. This randomized, placebo-controlled, double-blinded clinical trial is designed to determine whether "local" or "centrally-acting" treatments alone, or in combination are efficacious in treating vulvar vestibulitis. Outcome measures of success will include reduced overall pain, reduced pain to touch, reduced pain to standardized mechanical stimuli, increased painfree intercourse, improved sexual function, improved quality-of-life as measured by psychometric tests, and adherence to active drug regimens. The second major aim of this application is to study the relationship among genetic polymorphisms of the IL-1 Receptor Antagonist locus, tissue levels of pro-inflammatory cytokines, and response to treatment of vulvar vestibulitis. Pro-inflammatory cytokines, such as interleukin-I beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), are secreted from a local cellular source and accumulate above normal levels in the region of the hymeneal ring. Recent genetic analysis finds a 53% homozygosity for allele 2 IL-1 Receptor Antagonist (IL-1 RA*2) in cases of vulvar vestibulitis, in contrast to 8.5% homozygosity in asymptomatic women. Furthermore, the IL-1 RA*2 allele has been linked to increased production of IL-1 beta in vitro. In our second aim, we will determine whether these in vitro results can be extrapolated to clinical cases of vulvar vestibulitis. Using samples from our clinical trial, we will assess the relationship between homozygosity for IL-1 RA*2, tissue levels of IL-1 beta, and TNF-alpha, and response to treatment. In summary, this project will allow us to answer several important questions about vulvar vestibulitis. Is medical treatment effective? Is centrally-acting or locally-acting treatment equally effective or is one superior to the other? Is there any benefit from combined local and systemic treatments? And finally, do genetic characteristics and tissue cytokine concentrations influence treatment response? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 “desipramine” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for desipramine in the PubMed Central database: •

Effect of Citalopram on Blood Desipramine Levels. by Gupta S, Masand PS.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181108

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 desipramine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “desipramine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for desipramine (hyperlinks lead to article summaries): •

A 13 year old with desipramine ingestion. Author(s): Woolf PK. Source: Pediatric Emergency Care. 1993 August; 9(4): 239-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8367364

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A comparison of weight changes with fluoxetine, desipramine, and amitriptyline: a retrospective study of psychiatric inpatients. Author(s): Szarek BL, Brandt DM. Source: The Journal of Nervous and Mental Disease. 1993 November; 181(11): 702-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8228953

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 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 controlled trial of fluoxetine and desipramine in depressed women with advanced cancer. Author(s): Holland JC, Romano SJ, Heiligenstein JH, Tepner RG, Wilson MG. Source: Psycho-Oncology. 1998 July-August; 7(4): 291-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741068

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A double-blind comparison of clomipramine and desipramine in the treatment of developmental stuttering. Author(s): Gordon CT, Cotelingam GM, Stager S, Ludlow CL, Hamburger SD, Rapoport JL. Source: The Journal of Clinical Psychiatry. 1995 June; 56(6): 238-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7775365

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A double-blind comparison of clomipramine and desipramine treatment of severe onychophagia (nail biting). Author(s): Leonard HL, Lenane MC, Swedo SE, Rettew DC, Rapoport JL. Source: Archives of General Psychiatry. 1991 September; 48(9): 821-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1929772

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A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Author(s): Gordon CT, State RC, Nelson JE, Hamburger SD, Rapoport JL. Source: Archives of General Psychiatry. 1993 June; 50(6): 441-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8498878

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A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Author(s): Spencer T, Biederman J, Coffey B, Geller D, Crawford M, Bearman SK, Tarazi R, Faraone SV. Source: Archives of General Psychiatry. 2002 July; 59(7): 649-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12090818

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A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression. Author(s): Roth D, Mattes J, Sheehan KH, Sheehan DV. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1990; 14(6): 929-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2126144

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A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder. Author(s): Sasson Y, Iancu I, Fux M, Taub M, Dannon PN, Zohar J. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1999 March; 9(3): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10208287

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A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder. Author(s): Leonard HL, Swedo SE, Lenane MC, Rettew DC, Cheslow DL, Hamburger SD, Rapoport JL. Source: Archives of General Psychiatry. 1991 October; 48(10): 922-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1929762

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A double-blind placebo controlled study of desipramine in the treatment ADD: II. Serum drug levels and cardiovascular findings. Author(s): Biederman J, Baldessarini RJ, Wright V, Knee D, Harmatz JS, Goldblatt A. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1989 November; 28(6): 903-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2808261

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A double-blind placebo controlled study of desipramine in the treatment of ADD: I. Efficacy. Author(s): Biederman J, Baldessarini RJ, Wright V, Knee D, Harmatz JS. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1989 September; 28(5): 777-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2676967

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A double-blind placebo controlled study of desipramine in the treatment of ADD: III. Lack of impact of comorbidity and family history factors on clinical response. Author(s): Biederman J, Baldessarini RJ, Wright V, Keenan K, Faraone S. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 January; 32(1): 199-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8428872

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A double-blind trial of bupropion versus desipramine for bipolar depression. Author(s): Sachs GS, Lafer B, Stoll AL, Banov M, Thibault AB, Tohen M, Rosenbaum JF. Source: The Journal of Clinical Psychiatry. 1994 September; 55(9): 391-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7929019

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A double-blind, placebo-controlled trial of desipramine for primary alcohol dependence stratified on the presence or absence of major depression. Author(s): Mason BJ, Kocsis JH, Ritvo EC, Cutler RB. Source: Jama : the Journal of the American Medical Association. 1996 March 13; 275(10): 761-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8598592

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A naturalistic study of 24-hour electrocardiographic recordings and echocardiographic findings in children and adolescents treated with desipramine. Author(s): Biederman J, Baldessarini RJ, Goldblatt A, Lapey KA, Doyle A, Hesslein PS. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 July; 32(4): 805-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8340302

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A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Author(s): Nelson JC, Mazure CM, Bowers MB Jr, Jatlow PI. Source: Archives of General Psychiatry. 1991 April; 48(4): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2009031

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A study of the effects of desipramine treatment alone and in combination with Ltriiodothyronine on 6-sulphatoxymelatonin excretion in depressed patients. Author(s): Bearn J, Franey C, Arendt J, Checkley SA. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1989 September; 155: 341-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2611544

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Absence of effect of stimulants on the phamacokinetics of desipramine in children. Author(s): Cohen LG, Prince J, Biederman J, Wilens T, Faraone SV, Whitt S, Mick E, Spencer T, Meyer MC, Polisner D, Flood JG. Source: Pharmacotherapy. 1999 June; 19(6): 746-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10391421

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Acute noradrenergic effects of desipramine in depression. Author(s): Rudorfer MV, Sherer MA, Lane EA, Golden RN, Linnoila M, Potter WZ. Source: Journal of Clinical Psychopharmacology. 1991 February; 11(1): 22-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2040714

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Acute response of social functioning in dysthymic patients with desipramine. Author(s): Friedman RA, Markowitz JC, Parides M, Kocsis JH. Source: Journal of Affective Disorders. 1995 May 17; 34(2): 85-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7665809

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Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder. Author(s): Barr LC, Goodman WK, Anand A, McDougle CJ, Price LH. Source: The American Journal of Psychiatry. 1997 September; 154(9): 1293-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9286191

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Adjunctive desipramine in the treatment of cocaine abusing schizophrenics. Author(s): Ziedonis D, Richardson T, Lee E, Petrakis I, Kosten T. Source: Psychopharmacology Bulletin. 1992; 28(3): 309-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1480735

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Adolescent depression: controlled desipramine treatment and atypical features. Author(s): Klein RG, Mannuzza S, Koplewicz HS, Tancer NK, Shah M, Liang V, Davies M. Source: Depression and Anxiety. 1998; 7(1): 15-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9592629

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Adult attention deficit hyperactivity disorder and desipramine. Author(s): Magee R, Maier D, Reesal RT. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1992 March; 37(2): 148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1562962

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Adverse effects of switching from fluoxetine to desipramine. Author(s): Van Ameringen M, Mancini C. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1992 May; 37(4): 278. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611591

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An interaction of sertraline and desipramine. Author(s): Barros J, Asnis G. Source: The American Journal of Psychiatry. 1993 November; 150(11): 1751. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8214190

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Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population. Author(s): Dahl ML, Johansson I, Palmertz MP, Ingelman-Sundberg M, Sjoqvist F. Source: Clinical Pharmacology and Therapeutics. 1992 January; 51(1): 12-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1346258

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Another sudden death in a child treated with desipramine. Author(s): Riddle MA, Geller B, Ryan N. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 July; 32(4): 792-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8340300

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Anticholinergic toxic syndrome with venlafaxine-desipramine combination. Author(s): Benazzi F. Source: Pharmacopsychiatry. 1998 January; 31(1): 36-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9524985

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Behavioural evidence for supersensitivity of postsynaptic dopamine receptors in the mesolimbic system after chronic administration of desipramine. Author(s): Spyraki C, Fibiger HC. Source: European Journal of Pharmacology. 1981 September 11; 74(2-3): 195-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7198991

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Beta-receptor responsiveness after desipramine treatment. Author(s): Pohl R, Pandey GN, Yeragani VK, Balon R, Davis JM, Berchou R. Source: Psychopharmacology. 1993; 110(1-2): 37-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7870896

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Biological markers of affective disorders and posttraumatic stress disorder: a pilot study with desipramine. Author(s): Kauffman CD, Reist C, Djenderedjian A, Nelson JN, Haier RJ. Source: The Journal of Clinical Psychiatry. 1987 September; 48(9): 366-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3114242

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Blockade by imipramine or desipramine of panic induced by sodium lactate. Author(s): Rifkin A, Klein DF, Dillon D, Levitt M. Source: The American Journal of Psychiatry. 1981 May; 138(5): 676-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7235068

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Bromocriptine-desipramine protocol in treatment of cocaine addiction. Author(s): Giannini AJ, Billett W. Source: Journal of Clinical Pharmacology. 1987 August; 27(8): 549-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3308977

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Bulimia: independence of antibulimic and antidepressant properties of desipramine. Author(s): Blouin J, Blouin A, Perez E, Barlow J. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1989 February; 34(1): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2647270

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Cardiac beta-adrenergic sensitivity in depression: relation with endogenous subtype and desipramine response. Author(s): Bertschy G, Vandel S, Puech A, Vandel B, Sandoz M, Allers G. Source: Neuropsychobiology. 1989; 21(4): 177-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2561009

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Cardiac effects of desipramine. Author(s): Waslick B. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1995 February; 34(2): 125-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7534755

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Cardiovascular effects of desipramine in children and adults during exercise testing. Author(s): Waslick BD, Walsh BT, Greenhill LL, Giardina EG, Sloan RP, Bigger JT, Bilich K. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1999 February; 38(2): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9951217

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Cardiovascular effects of desipramine in children. Author(s): Schroeder JS, Mullin AV, Elliott GR, Steiner H, Nichols M, Gordon A, Paulos M. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1989 May; 28(3): 376-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2661525

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Central analgesic effects of desipramine, fluvoxamine, and moclobemide after single oral dosing: a study in healthy volunteers. Author(s): Coquoz D, Porchet HC, Dayer P. Source: Clinical Pharmacology and Therapeutics. 1993 September; 54(3): 339-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8375130

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Cerebral blood flow in obsessive-compulsive patients with major depression: effect of treatment with sertraline or desipramine on treatment responders and nonresponders. Author(s): Hoehn-Saric R, Schlaepfer TE, Greenberg BD, McLeod DR, Pearlson GD, Wong SH. Source: Psychiatry Research. 2001 November 30; 108(2): 89-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11738543

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Changes in thyroid hormone levels associated with desipramine response in adolescent depression. Author(s): Sokolov ST, Kutcher SP, Joffe RT. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1996 August; 20(6): 1053-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8888110

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Characteristics of desipramine-refractory depression. Author(s): Nelson JC, Mazure CM, Jatlow PI. Source: The Journal of Clinical Psychiatry. 1994 January; 55(1): 12-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8294386

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chi-Conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter. Author(s): Bryan-Lluka LJ, Bonisch H, Lewis RJ. Source: The Journal of Biological Chemistry. 2003 October 10; 278(41): 40324-9. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837768

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Clinical and neuropsychological effects of desipramine in children with attention deficit hyperactivity disorder. Author(s): Gualtieri CT, Keenan PA, Chandler M. Source: Journal of Clinical Psychopharmacology. 1991 June; 11(3): 155-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2066453

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Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. Author(s): Ciraulo DA, Barnhill JG, Jaffe JH. Source: Clinical Pharmacology and Therapeutics. 1988 May; 43(5): 509-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3365915

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Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness. Author(s): Hollander E, Allen A, Kwon J, Aronowitz B, Schmeidler J, Wong C, Simeon D. Source: Archives of General Psychiatry. 1999 November; 56(11): 1033-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565503

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Clonazepam-induced reduction in serum desipramine concentration. Author(s): Deicken RF. Source: Journal of Clinical Psychopharmacology. 1988 February; 8(1): 71-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3351006

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Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Author(s): Drossman DA, Toner BB, Whitehead WE, Diamant NE, Dalton CB, Duncan S, Emmott S, Proffitt V, Akman D, Frusciante K, Le T, Meyer K, Bradshaw B, Mikula K, Morris CB, Blackman CJ, Hu Y, Jia H, Li JZ, Koch GG, Bangdiwala SI. Source: Gastroenterology. 2003 July; 125(1): 19-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851867

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Combined fluoxetine and desipramine in resistant depression. Author(s): Horgan D. Source: The Australian and New Zealand Journal of Psychiatry. 1993 March; 27(1): 166, 168. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8481163

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Combining fluoxetine with desipramine. Author(s): DeMaso DR, Hunter TA. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1990 January; 29(1): 151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2295572

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Comorbid major depressive disorder as a prognostic factor in cocaine-abusing buprenorphine-maintained patients treated with desipramine and contingency management. Author(s): Gonzalez G, Feingold A, Oliveto A, Gonsai K, Kosten TR. Source: The American Journal of Drug and Alcohol Abuse. 2003 August; 29(3): 497-514. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510037

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Comparative plasma levels of doxepin and desipramine in the elderly. Author(s): Gosselin C, Ancill RJ. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1989 December; 34(9): 921, 923-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2611758

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Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. Author(s): Weddington WW Jr, Brown BS, Haertzen CA, Hess JM, Mahaffey JR, Kolar AF, Jaffe JH. Source: The American Journal of Drug and Alcohol Abuse. 1991 June; 17(2): 137-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1862788

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Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. Author(s): Weddington WW, Brown BS, Haertzen CA, Hess JM, Kolar AF, Mahaffey JR. Source: Nida Res Monogr. 1989; 95: 483-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2701321

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Comparison of cognitive-behavior therapy and desipramine in the treatment of bulimia nervosa. Author(s): Leitenberg H, Rosen JC, Wolf J, Vara LS, Detzer MJ, Srebnik D. Source: Behaviour Research and Therapy. 1994 January; 32(1): 37-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8135721

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Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mild-to-moderate depression. Author(s): Thompson LW, Coon DW, Gallagher-Thompson D, Sommer BR, Koin D. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2001 Summer; 9(3): 225-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11481130

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Comparison of desipramine or carbamazepine to placebo for crack cocaine-dependent patients. Author(s): Campbell J, Nickel EJ, Penick EC, Wallace D, Gabrielli WF, Rowe C, Liskow B, Powell BJ, Thomas HM. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2003 March-April; 12(2): 122-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746087

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Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans. Author(s): Skene DJ, Bojkowski CJ, Arendt J. Source: British Journal of Clinical Pharmacology. 1994 February; 37(2): 181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8186063

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Comparison of the effects of desipramine on noradrenaline- and methoxamineevoked venoconstriction in man. Author(s): Abdelmawla AH, Langley RW, Szabadi E, Bradshaw CM. Source: British Journal of Clinical Pharmacology. 1995 November; 40(5): 445-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8703648

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Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein. Author(s): Abdelmawla AH, Langley RW, Szabadi E, Bradshaw CM. Source: British Journal of Clinical Pharmacology. 1999 September; 48(3): 345-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10510145

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Comparison of the effects of venlafaxine, paroxetine and desipramine on the pupillary light reflex in man. Author(s): Bitsios P, Szabadi E, Bradshaw CM. Source: Psychopharmacology. 1999 April; 143(3): 286-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10353432

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Concurrent liquid chromatographic measurement of fluoxetine, amitriptyline, imipramine, and their active metabolites norfluoxetine, nortriptyline, and desipramine in plasma. Author(s): el-Yazigi A, Raines DA. Source: Therapeutic Drug Monitoring. 1993 August; 15(4): 305-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8236366

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Concurrent treatment of nonresistant major depression with desipramine and lithium: a double-blind, placebo-controlled study. Author(s): Bloch M, Schwartzman Y, Bonne O, Lerer B. Source: Journal of Clinical Psychopharmacology. 1997 February; 17(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9004056

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Continuity of care and desipramine in primary cocaine abusers. Author(s): Hall SM, Tunis S, Triffleman E, Banys P, Clark HW, Tusel D, Stewart P, Presti D. Source: The Journal of Nervous and Mental Disease. 1994 October; 182(10): 570-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7931205

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Dangerous interaction with nefazodone added to fluoxetine, desipramine, venlafaxine, valproate and clonazepam combination therapy. Author(s): Benazzi F. Source: Journal of Psychopharmacology (Oxford, England). 1997; 11(2): 190-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9208383

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Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms. Author(s): Swanson JR, Jones GR, Krasselt W, Denmark LN, Ratti F. Source: J Forensic Sci. 1997 March; 42(2): 335-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9068197

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Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone. Author(s): Yatham LN, Liddle PF, Dennie J, Shiah IS, Adam MJ, Lane CJ, Lam RW, Ruth TJ. Source: Archives of General Psychiatry. 1999 August; 56(8): 705-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435604

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Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients. Author(s): Kosten T, Oliveto A, Feingold A, Poling J, Sevarino K, McCance-Katz E, Stine S, Gonzalez G, Gonsai K. Source: Drug and Alcohol Dependence. 2003 June 5; 70(3): 315-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757969

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Desipramine and ibuprofen. Author(s): Gillette DW. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1998 November; 37(11): 1129. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9808920

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Desipramine and the EKG. Author(s): Smith RH. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1992 May; 31(3): 564-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1592794

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Desipramine binding to noradrenaline reuptake sites in cardiac sympathetic neurons in man in vivo. Author(s): Malizia AL, Melichar JK, Rhodes CG, Haida A, Reynolds AH, Jones T, Nutt DJ. Source: European Journal of Pharmacology. 2000 March 17; 391(3): 263-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10729367

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Desipramine clearance in children and adolescents: absence of effect of development and gender. Author(s): Cohen LG, Biederman J, Wilens TE, Spencer TJ, Mick E, Faraone SV, Prince J, Flood JG. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1999 January; 38(1): 79-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9893420

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Desipramine facilitation of cocaine abstinence in an adolescent. Author(s): Kaminer Y. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1992 March; 31(2): 312-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1314257

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Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. Author(s): Oliveto AH, Feingold A, Schottenfeld R, Jatlow P, Kosten TR. Source: Archives of General Psychiatry. 1999 September; 56(9): 812-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884887

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Desipramine lowers tritiated para-aminoclonidine binding in platelets of depressed patients. Author(s): Piletz JE, Halaris A, Saran A, Marler MR. Source: Archives of General Psychiatry. 1991 September; 48(9): 813-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1681792

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Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers. Author(s): Alderman J, Preskorn SH, Greenblatt DJ, Harrison W, Penenberg D, Allison J, Chung M. Source: Journal of Clinical Psychopharmacology. 1997 August; 17(4): 284-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9241008

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Desipramine side-effect. Author(s): Mosholder A, Bates C. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1991 November; 30(6): 1026. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1757433

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Desipramine toxicity with terbinafine. Author(s): O'Reardon JP, Hetznecker JM, Rynn MA, Baldassano CF, Szuba MP. Source: The American Journal of Psychiatry. 2002 March; 159(3): 492. Erratum In: Am J Psychiatry 2002 June; 159(6): 1076. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870022

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Desipramine treatment decreases 3H-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells. Author(s): Zavosh A, Schaefer J, Ferrel A, Figlewicz DP. Source: Brain Research Bulletin. 1999 July 1; 49(4): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10424850

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Desipramine treatment in panic disorder. Author(s): Kalus O, Asnis GM, Rubinson E, Kahn R, Friedman JM, Iqbal N, Grosz D, van Praag H, Cahn W. Source: Journal of Affective Disorders. 1991 April; 21(4): 239-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1829745

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Desipramine versus phenelzine in recurrent unipolar depression: clinical characteristics and treatment response. Author(s): Swann AC, Bowden CL, Rush AJ, Rhoades H, Rose R, Kobes R. Source: Journal of Clinical Psychopharmacology. 1997 April; 17(2): 78-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950467

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Desipramine, amantadine, or fluoxetine in buprenorphine-maintained cocaine users. Author(s): Oliveto A, Kosten TR, Schottenfeld R, Falcioni J, Ziedonis D. Source: Journal of Substance Abuse Treatment. 1995 November-December; 12(6): 423-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749726

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Desipramine-induced urticaria: a clinical problem. Author(s): Bajwa WK, Asnis GM. Source: The Journal of Nervous and Mental Disease. 1991 February; 179(2): 108-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1824949

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Determination of imipramine, desipramine and their hydroxy metabolites by reversed-phase chromatography with ultraviolet and coulometric detection. Author(s): Foglia JP, Sorisio D, Perel JM. Source: Journal of Chromatography. 1991 December 6; 572(1-2): 247-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1818058

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Developmental changes in serum concentrations of desipramine and 2hydroxydesipramine during treatment with desipramine. Author(s): Wilens TE, Biederman J, Baldessarini RJ, Puopolo PR, Flood JG. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1992 July; 31(4): 691-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1644733

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Different effect of desipramine on protein kinase C in platelets between bipolar and major depressive disorders. Author(s): Morishita S, Aoki S, Watanabe S. Source: Psychiatry and Clinical Neurosciences. 1999 February; 53(1): 11-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10201278

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Differential response of seven subjects with autistic disorder to clomipramine and desipramine. Author(s): Gordon CT, Rapoport JL, Hamburger SD, State RC, Mannheim GB. Source: The American Journal of Psychiatry. 1992 March; 149(3): 363-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1536276

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Dosage optimization methods applied to imipramine and desipramine in enuresis treatment. Author(s): Tamayo M, Fernandez de Gatta MM, Garcia MJ, Dominguez-Gil A. Source: Journal of Clinical Pharmacy and Therapeutics. 1992 February; 17(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1548314

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Double-blind comparison of fluoxetine and desipramine in the treatment of depressed women with advanced HIV disease: a pilot study. Author(s): Schwartz JA, McDaniel JS. Source: Depression and Anxiety. 1999; 9(2): 70-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10207661

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Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. Author(s): Fava M, Alpert J, Nierenberg A, Lagomasino I, Sonawalla S, Tedlow J, Worthington J, Baer L, Rosenbaum JF. Source: Journal of Clinical Psychopharmacology. 2002 August; 22(4): 379-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172337

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Down-regulation of the human norepinephrine transporter in intact 293-hNET cells exposed to desipramine. Author(s): Zhu MY, Blakely RD, Apparsundaram S, Ordway GA. Source: Journal of Neurochemistry. 1998 April; 70(4): 1547-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9523572

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Duplication of CYP2D6 predicts high clearance of desipramine but high clearance does not predict duplication of CYP2D6. Author(s): Bergmann TK, Bathum L, Brosen K. Source: European Journal of Clinical Pharmacology. 2001 May; 57(2): 123-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11417443

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ECG changes in pediatric patients on tricyclic antidepressants, desipramine, and imipramine. Author(s): Johnson A, Giuffre RM, O'Malley K. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1996 March; 41(2): 102-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8705955

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Effect of desipramine on norepinephrine metabolism in humans: interaction with aging. Author(s): Stromberg JS, Linares OA, Supiano MA, Smith MJ, Foster AH, Halter JB. Source: The American Journal of Physiology. 1991 December; 261(6 Pt 2): R1484-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1750571

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Effect of fluoxetine on plasma desipramine and 2-hydroxydesipramine. Author(s): Suckow RF, Roose SP, Cooper TB. Source: Biological Psychiatry. 1992 January 15; 31(2): 200-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1737080

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Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects. Author(s): Spina E, Avenoso A, Campo GM, Scordo MG, Caputi AP, Perucca E. Source: British Journal of Clinical Pharmacology. 1997 March; 43(3): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9088587

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Effect of polypropylene centrifuge tubes on extraction of desipramine from blood. Author(s): Argenti D, D'mello A. Source: Clinical Chemistry. 1991 August; 37(8): 1468. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1868619

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Effect of terbinafine on the pharmacokinetics and pharmacodynamics of desipramine in healthy volunteers identified as cytochrome P450 2D6 (CYP2D6) extensive metabolizers. Author(s): Madani S, Barilla D, Cramer J, Wang Y, Paul C. Source: Journal of Clinical Pharmacology. 2002 November; 42(11): 1211-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412819

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Effect of the antidepressant desipramine on cytosolic Ca(2+) movement and proliferation in human osteosarcoma cells. Author(s): Jan CR, Lu YC, Tseng LL, Jiann BP, Chang HT, Wang JL, Chen WC, Huang JK. Source: Pharmacology. 2003 December; 69(4): 190-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624059

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Effect of the novel anxiolytic drug deramciclane on cytochrome P(450) 2D6 activity as measured by desipramine pharmacokinetics. Author(s): Laine K, De Bruyn S, Bjorklund H, Rouru J, Hanninen J, Scheinin H, Anttila M. Source: European Journal of Clinical Pharmacology. 2004 February; 59(12): 893-8. Epub 2004 January 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730412

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Effect of tolcapone on the haemodynamic effects and tolerability of desipramine. Author(s): Jorga KM, Fotteler B, Modi M, Rabbia M. Source: European Neurology. 2000; 44(2): 94-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10965161

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Effects of desipramine on autonomic input to the heart. Author(s): Walsh BT, Greenhill LL, Giardina EG, Bigger JT, Waslick BD, Sloan RP, Bilich K, Wolk S, Bagiella E. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1999 September; 38(9): 1186-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10504819

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Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans. Author(s): Esler MD, Wallin G, Dorward PK, Eisenhofer G, Westerman R, Meredith I, Lambert G, Cox HS, Jennings G. Source: The American Journal of Physiology. 1991 April; 260(4 Pt 2): R817-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2012253

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Effects of desipramine treatment on norepinephrine transporter gene expression in the cultured SK-N-BE(2)M17 cells and rat brain tissue. Author(s): Zhu MY, Kim CH, Hwang DY, Baldessarini RJ, Kim KS. Source: Journal of Neurochemistry. 2002 July; 82(1): 146-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091475

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Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. Author(s): Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner R. Source: The New England Journal of Medicine. 1992 May 7; 326(19): 1250-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1560801

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Effects of electroconvulsive therapy and desipramine on neuroendocrine responses to the clonidine challenge test. Author(s): Coote M, Wilkins A, Werstiuk ES, Steiner M. Source: Journal of Psychiatry & Neuroscience : Jpn. 1998 May; 23(3): 172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9595891

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Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder. Author(s): Overtoom CC, Verbaten MN, Kemner C, Kenemans JL, van Engeland H, Buitelaar JK, van der Molen MW, van der Gugten J, Westenberg H, Maes RA, Koelega HS. Source: Behavioural Brain Research. 2003 October 17; 145(1-2): 7-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529800

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Effects of reducing contingency management values on heroin and cocaine use for buprenorphine- and desipramine-treated patients. Author(s): Kosten T, Poling J, Oliveto A. Source: Addiction (Abingdon, England). 2003 May; 98(5): 665-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751984

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Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Author(s): Max MB, Kishore-Kumar R, Schafer SC, Meister B, Gracely RH, Smoller B, Dubner R. Source: Pain. 1991 April; 45(1): 3-9; Discussion 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1861872

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Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents. Author(s): Leonard HL, Meyer MC, Swedo SE, Richter D, Hamburger SD, Allen AJ, Rapoport JL, Tucker E. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1995 November; 34(11): 1460-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8543513

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Estimation of the association between desipramine and the risk for sudden death in 5- to 14-year-old children. Author(s): Biederman J, Thisted RA, Greenhill LL, Ryan ND. Source: The Journal of Clinical Psychiatry. 1995 March; 56(3): 87-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7883735

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Extremely slow metabolism of amitriptyline but normal metabolism of imipramine and desipramine in an extensive metabolizer of sparteine, debrisoquine, and mephenytoin. Author(s): Brosen K, Gram LF, Kragh-Sorensen P. Source: Therapeutic Drug Monitoring. 1991 March; 13(2): 177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2053127

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First-pass metabolism of imipramine and desipramine: impact of the sparteine oxidation phenotype. Author(s): Brosen K, Gram LF. Source: Clinical Pharmacology and Therapeutics. 1988 April; 43(4): 400-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3356084

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Fluency changes in persons who stutter following a double blind trial of clomipramine and desipramine. Author(s): Stager SV, Ludlow CL, Gordon CT, Cotelingam M, Rapoport JL. Source: Journal of Speech and Hearing Research. 1995 June; 38(3): 516-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7674643

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Fluoxetine and desipramine in major depressive disorder. Author(s): Bowden CL, Schatzberg AF, Rosenbaum A, Contreras SA, Samson JA, Dessain E, Sayler M. Source: Journal of Clinical Psychopharmacology. 1993 October; 13(5): 305-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8227488

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Fluoxetine and desipramine: a strategy for augmenting anti-depressant response. Author(s): Eisen A. Source: Pharmacopsychiatry. 1989 November; 22(6): 272-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2616636

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Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression. Author(s): Bell IR, Cole JO. Source: Journal of Clinical Psychopharmacology. 1988 December; 8(6): 447-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3266222

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Fluoxetine inhibits desipramine metabolism. Author(s): Wilens TE, Biederman J, Baldessarini RJ, McDermott SP, Puopolo PR, Flood JG. Source: Archives of General Psychiatry. 1992 September; 49(9): 752. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1514882

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Fluvoxamine versus desipramine: comparative polysomnographic effects. Author(s): Kupfer DJ, Perel JM, Pollock BG, Nathan RS, Grochocinski VJ, Wilson MJ, McEachran AB. Source: Biological Psychiatry. 1991 January 1; 29(1): 23-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1900443

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Fluvoxamine-induced alterations in plasma concentrations of imipramine and desipramine in depressed patients. Author(s): Spina E, Pollicino AM, Avenoso A, Campo GM, Caputi AP. Source: Int J Clin Pharmacol Res. 1993; 13(3): 167-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8225700

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Formation of cytotoxic metabolites from phenytoin, imipramine, desipramine, amitriptyline and mianserin by mouse and human hepatic microsomes. Author(s): Riley RJ, Roberts P, Kitteringham NR, Park BK. Source: Biochemical Pharmacology. 1990 June 15; 39(12): 1951-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2353936

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Gas chromatographic-mass fragmentographic determation of "steady-state" plasma levels of imipramine and desipramine in chronically treated patients. Author(s): Belvedere G, Burti L, Frigerio A, Pantarotto C. Source: Journal of Chromatography. 1975 September 3; 111(2): 313-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1159010

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Genetically determined drug-metabolizing activity and desipramine-associated cardiotoxicity: a case report. Author(s): Bluhm RE, Wilkinson GR, Shelton R, Branch RA. Source: Clinical Pharmacology and Therapeutics. 1993 January; 53(1): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8422746

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Growth deficits and desipramine. Author(s): Holt KG. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1992 November; 31(6): 1167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1429424

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Growth deficits in children treated with desipramine: a controlled study. Author(s): Spencer T, Biederman J, Wright V, Danon M. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1992 March; 31(2): 235-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1564024

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Growth hormone release after desipramine in depressive illness. Author(s): Meesters P, Kerkhofs M, Charles G, Decoster C, Vanderelst M, Mendlewicz J. Source: Eur Arch Psychiatry Neurol Sci. 1985; 235(3): 140-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4092710

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Growth of hyperkinetic children taking methylphenidate, dextroamphetamine, or imipramine/desipramine. Author(s): Millichap JG. Source: Pediatrics. 1978 January; 61(1): 146-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=263851

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Growth of hyperkinetic children taking methylphenidate, dextroamphetamine, or imipramine/desipramine. Author(s): Gross MD. Source: Pediatrics. 1976 September; 58(3): 423-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=958770

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Haloperidol-desipramine interaction in mice, rats and man. Author(s): Morselli PL, Rizzo M, Zaccala M, Garattini S. Source: Chemico-Biological Interactions. 1970 August; 2(2): 160-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5526730

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High dose desipramine, plasma drug levels and clinical response. Author(s): Amsterdam J, Brunswick DJ, Mendels J. Source: The Journal of Clinical Psychiatry. 1979 March; 40(3): 141-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=33968

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High-performance liquid chromatographic assay for imipramine, desipramine, and their 2-hydroxylated metabolites. Author(s): Sutfin TA, Jusko WJ. Source: Journal of Pharmaceutical Sciences. 1979 June; 68(6): 703-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=458567

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High-performance liquid chromatographic determination of imipramine and desipramine in human serum. Author(s): Kobayashi A, Sugita S, Nakazawa K. Source: Journal of Chromatography. 1984 December 12; 336(2): 410-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6530474

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Hormonal responses to zimelidine and desipramine in depressed patients. Author(s): Calil HM, Lesieur P, Gold PW, Brown GM, Zavadil AP 3rd, Potter WZ. Source: Psychiatry Research. 1984 November; 13(3): 231-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6098913

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Hyperactive phosphoinositide signaling pathway in platelets of depressed patients: effect of desipramine treatment. Author(s): Pandey GN, Ren X, Pandey SC, Dwivedi Y, Sharma R, Janicak PG. Source: Psychiatry Research. 2001 December 15; 105(1-2): 23-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740972

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Hyperpyrexia in an adolescent on desipramine treatment. Author(s): Squires LA, Neumeyer AM, Bloomberg J, Krishnamoorthy KS. Source: Clinical Pediatrics. 1992 October; 31(10): 635-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1395373

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Hypersensitivity myocarditis and hepatitis associated with imipramine and its metabolite, desipramine. Author(s): Morrow PL, Hardin NJ, Bonadies J. Source: J Forensic Sci. 1989 July; 34(4): 1016-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2760582

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Hypersensitivity reaction to desipramine. Author(s): Panuska JR, King TR, Korenblat PE, Wedner HJ. Source: The Journal of Allergy and Clinical Immunology. 1987 July; 80(1): 18-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3598027

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Hypomania after desipramine withdrawal. Author(s): Nelson JC, Schottenfeld RS, Conrad CD. Source: The American Journal of Psychiatry. 1983 May; 140(5): 624-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6846597

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Imipramine hydrochloride and desipramine hydrochloride as new reagents for detection of microamounts of blood in urine. Author(s): Syed AA, Silwadi MF, Khatoon BA. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 May 15; 28(3-4): 501-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008129

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Immunoassay reagents for psychoactive drugs. Part 5. Quantitative determination of imipramine and desipramine by fluorescence polarization immunoassay. Author(s): Adamczyk M, Fishpaugh JR, Harrington CA, Orsulak P, Akers L. Source: Therapeutic Drug Monitoring. 1994 December; 16(6): 577-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7878697

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Impact of desipramine or carbamazepine on patient retention in outpatient cocaine treatment: preliminary findings. Author(s): Campbell JL, Thomas HM, Gabrielli W, Liskow BI, Powell BJ. Source: Journal of Addictive Diseases : the Official Journal of the Asam, American Society of Addiction Medicine. 1994; 13(4): 191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7734469

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Increase in desipramine serum levels associated with methadone treatment. Author(s): Maany I, Dhopesh V, Arndt IO, Burke W, Woody G, O'Brien CP. Source: The American Journal of Psychiatry. 1989 December; 146(12): 1611-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2486749

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Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa. Author(s): Walsh BT, Hadigan CM, Wong LM. Source: Journal of Clinical Psychopharmacology. 1992 June; 12(3): 163-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1629381

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Influence of clenbuterol, a beta-adrenergic agonist, on desipramine induced growth hormone, prolactin and cortisol stimulation. Author(s): Laakmann G, Munz T, Hinz A, Voderholzer U. Source: Psychoneuroendocrinology. 1990; 15(5-6): 391-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2101962

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Influence of fluoxetine on plasma levels of desipramine. Author(s): Goodnick PJ. Source: The American Journal of Psychiatry. 1989 April; 146(4): 552. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2784633

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Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Author(s): Brosen K, Hansen JG, Nielsen KK, Sindrup SH, Gram LF. Source: European Journal of Clinical Pharmacology. 1993; 44(4): 349-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8513845

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Inhibition by vitamin E of drug accumulation and of phospholipidosis induced by desipramine and other cationic amphiphilic drugs in human cultured cells. Author(s): Scuntaro I, Kientsch U, Wiesmann UN, Honegger UE. Source: British Journal of Pharmacology. 1996 November; 119(5): 829-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8922728

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Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. Author(s): von Moltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI. Source: Journal of Clinical Psychopharmacology. 1995 April; 15(2): 125-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7782485

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Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. Author(s): von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI. Source: Journal of Pharmaceutical Sciences. 1998 October; 87(10): 1184-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9758674

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Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. Author(s): von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, Shader RI. Source: The Journal of Pharmacology and Experimental Therapeutics. 1994 March; 268(3): 1278-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8138941

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Inhibition of neuronal nicotinic acetylcholine receptors by imipramine and desipramine. Author(s): Rana B, McMorn SO, Reeve HL, Wyatt CN, Vaughan PF, Peers C. Source: European Journal of Pharmacology. 1993 December 7; 250(2): 247-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7509283

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Inhibition of SK3 channels in the TE671 human medulloblastoma cell line by desipramine and imipramine. Author(s): Carignani C, Corsi M. Source: European Journal of Pharmacology. 2002 July 19; 448(2-3): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12144933

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Inhibition of transport function and desipramine binding at the human noradrenaline transporter by N-ethylmaleimide and protection by substrate analogs. Author(s): Foley KF, Cozzi NV. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2002 June; 365(6): 457-61. Epub 2002 April 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12070759

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Interaction between fluvoxamine and imipramine/desipramine in four patients. Author(s): Spina E, Campo GM, Avenoso A, Pollicino MA, Caputi AP. Source: Therapeutic Drug Monitoring. 1992 June; 14(3): 194-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1412604

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Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine. Author(s): Kolzer M, Werth N, Sandhoff K. Source: Febs Letters. 2004 February 13; 559(1-3): 96-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960314

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Interindividual variability in the N-sulphation of desipramine in human liver and platelets. Author(s): Romiti P, Giuliani L, Pacifici GM. Source: British Journal of Clinical Pharmacology. 1992 January; 33(1): 17-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1540485

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Interpersonal improvement in chronically depressed patients treated with desipramine. Author(s): Markowitz JC, Friedman RA, Miller N, Spielman LA, Moran ME, Kocsis JH. Source: Journal of Affective Disorders. 1996 November 4; 41(1): 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938206

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Isolation of partially purified P450 2D18 and characterization of activity toward the tricyclic antidepressants imipramine and desipramine. Author(s): Thompson CM, Kawashima H, Strobel HW. Source: Archives of Biochemistry and Biophysics. 1998 November 1; 359(1): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9799568

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Lack of desipramine toxicity with citalopram. Author(s): Ashton AK. Source: The Journal of Clinical Psychiatry. 2000 February; 61(2): 144. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10732663

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Lack of effect of desipramine on the response to chloroquine of patients with chloroquine-resistant falciparum malaria. Author(s): Warsame M, Wernsdorfer WH, Bjorkman A. Source: Transactions of the Royal Society of Tropical Medicine and Hygiene. 1992 MayJune; 86(3): 235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1412641

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Lack of weight gain under desipramine. Author(s): Stern SL, Cooper TB, Johnson MH, Jones BA, Nelson LD, Smeltzer DJ. Source: Biological Psychiatry. 1987 June; 22(6): 796-7. Erratum In: Biol Psychiatry 1987 October; 22(10): 1299. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3593822

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Lethal hepatic necrosis after therapy with imipramine and desipramine. Author(s): Powell WJ Jr, Koch-Weser J, Williams RA. Source: Jama : the Journal of the American Medical Association. 1968 October 14; 206(3): 642-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4234079

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Lithium and desipramine versus desipramine alone in the treatment of severe major depression: a preliminary study. Author(s): Cappiello A, McDougle CJ, Delgado PL, Malison RT, Jatlow P, Charney DS, Heninger GR, Price LH. Source: International Clinical Psychopharmacology. 1998 September; 13(5): 191-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817623

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Lithium carbonate augmentation of desipramine and fluoxetine in refractory depression. Author(s): Fontaine R, Ontiveros A, Elie R, Vezina M. Source: Biological Psychiatry. 1991 May 1; 29(9): 946-8. Erratum In: Biol Psychiatry 1992 February 1; 31(3): 322. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1904782

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Lithium carbonate augmentation of desipramine in refractory depression. Author(s): Dallal A, Fontaine R, Ontiveros A, Elie R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1990 October; 35(7): 608-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2125237

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Lithium or desipramine augmentation of fluoxetine treatment. Author(s): Nelson JC, Price LH. Source: The American Journal of Psychiatry. 1995 October; 152(10): 1538-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7573606

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Liver function tests during treatment with desipramine in children and adolescents. Author(s): Hoge SK, Biederman J. Source: Journal of Clinical Psychopharmacology. 1987 April; 7(2): 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3584526

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Lofepramine, desipramine and abnormal tests of liver function: a case report. Author(s): Lack SJ, Baldwin DS, Montgomery SA. Source: International Clinical Psychopharmacology. 1990 July; 5(3): 185-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2230062

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Long-term downregulation of central adrenoceptor function by desipramine treatment: a clonidine study in normal subjects. Author(s): Schittecatte M, Charles G, Nefve C, Valentin JG, Machowski R, Wilmotte J. Source: Biological Psychiatry. 1992 April 15; 31(8): 856-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1322721

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Lorazepam and desipramine serum concentration. Author(s): Rosenblatt JE. Source: The American Journal of Psychiatry. 1982 April; 139(4): 536-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6121493

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Maintenance desipramine for dysthymia: a placebo-controlled study. Author(s): Miller NL, Kocsis JH, Leon AC, Portera L, Dauber S, Markowitz JC. Source: Journal of Affective Disorders. 2001 May; 64(2-3): 231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11313089

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Maintenance therapy for chronic depression. A controlled clinical trial of desipramine. Author(s): Kocsis JH, Friedman RA, Markowitz JC, Leon AC, Miller NL, Gniwesch L, Parides M. Source: Archives of General Psychiatry. 1996 September; 53(9): 769-74; Discussion 775-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792753

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Major adverse reactions during desipramine treatment: relationship to plasma drug concentrations, concomitant antipsychotic treatment, and patient characteristics. Author(s): Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowers MB Jr. Source: Archives of General Psychiatry. 1982 September; 39(9): 1055-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6126171

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MAO-A and MAO-B activities in rat striatum, frontal cortex and liver are unaltered after long-term treatment with fluvoxamine and desipramine. Author(s): Silver H, Youdim MB. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2000 March; 10(2): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10706994

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Massive eosinophilic reaction to desipramine in conjunction with pneumonia. Author(s): Kraus RP, Clarke RJ, Remick RA. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1984 March; 29(2): 142-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6722706

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Massive eosinophilic reaction to desipramine. Author(s): Jones DR, Maloney TR. Source: The American Journal of Psychiatry. 1980 January; 137(1): 115-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7352545

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Measurement of free desipramine in serum by ultrafiltration with immunoassay. Author(s): Hursting MJ, Clark GD, Raisys VA, Miller SJ, Opheim KE. Source: Clinical Chemistry. 1992 December; 38(12): 2468-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1458586

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Meta-analysis of desipramine as an adjunct in the treatment of cocaine addiction. Author(s): Levin FR, Lehman AF. Source: Journal of Clinical Psychopharmacology. 1991 December; 11(6): 374-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1837556

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Metabolism of desipramine in Japanese psychiatric patients: the impact of CYP2D6 genotype on the hydroxylation of desipramine. Author(s): Shimoda K, Morita S, Hirokane G, Yokono A, Someya T, Takahashi S. Source: Pharmacology & Toxicology. 2000 June; 86(6): 245-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895986

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Methylphenidate and desipramine in hospitalized children: I. Separate and combined effects on cognitive function. Author(s): Rapport MD, Carlson GA, Kelly KL, Pataki C. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 March; 32(2): 333-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8444762

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Moclobemide (Ro 11-1163) versus desipramine in the treatment of endogenous depression. Author(s): Gabelic I, Moll E. Source: Acta Psychiatrica Scandinavica. Supplementum. 1990; 360: 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2248068

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Monitoring of serum levels of imipramine and desipramine and individualization of dose in enuretic children. Author(s): de Gatta MF, Garcia MJ, Acosta A, Rey F, Gutierrez JR, Dominguez-Gil A. Source: Therapeutic Drug Monitoring. 1984; 6(4): 438-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6515703

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Multicenter double-blind comparison of sertraline and desipramine for concurrent obsessive-compulsive and major depressive disorders. Author(s): Hoehn-Saric R, Ninan P, Black DW, Stahl S, Greist JH, Lydiard B, McElroy S, Zajecka J, Chapman D, Clary C, Harrison W. Source: Archives of General Psychiatry. 2000 January; 57(1): 76-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10632236

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Myocardial toxicity produced by desipramine overdosage. Author(s): Chahine RA, Castellanos A Jr. Source: Chest. 1971 May; 59(5): 566-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4952559

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Neuroendocrine and other studies of the mechanism of antidepressant action of desipramine. Author(s): Checkley SA, Corn TH, Glass IB, Thompson C, Franey C, Arendt J. Source: Ciba Found Symp. 1986; 123: 126-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3028722

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Neuroendocrine response to clomipramine and desipramine--the evidence of partial determination by heredity and sex. Author(s): Filip V, Alda M, David I, Topinka J, Kristofikova Z, Dvorakova J, Sztaniszlav D, Olajos S, Albrecht V. Source: Neuropsychobiology. 1989; 21(3): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2615927

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Neuroleptic dose and desipramine concentrations during combined treatment of unipolar delusional depression. Author(s): Nelson JC, Price LH, Jatlow PI. Source: The American Journal of Psychiatry. 1986 September; 143(9): 1151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3752299

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Neuroloeptic effect on desipramine steady-state plasma concentratins. Author(s): Nelson JC, Jatlow PI. Source: The American Journal of Psychiatry. 1980 October; 137(10): 1232-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6106391

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No interaction between desipramine and bromperidol. Author(s): Suzuki A, Otani K, Ishida M, Yasui N, Kondo T, Mihara K, Kaneko S, Inoue Y. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1996 October; 20(7): 1265-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938825

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Nocturnal enuresis: remission in a patient treated with desipramine and protriptyline. Author(s): Ayres CM. Source: The American Journal of Psychiatry. 1966 February; 122(8): 947-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5902508

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Noninvasive measurement of cardiac ejection fraction during desipramine treatment. Author(s): Murburg M, Anton RF, Nelson JC, Jatlow PI. Source: Psychosomatics. 1982 July; 23(7): 759-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7122806

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Nonlinear desipramine kinetics: prevalence and importance. Author(s): Nelson JC, Jatlow PI. Source: Clinical Pharmacology and Therapeutics. 1987 June; 41(6): 666-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3581650

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Nonlinear desipramine pharmacokinetics: a case study. Author(s): Dugas JE, Bishop DS. Source: Journal of Clinical Psychopharmacology. 1985 February; 5(1): 43-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3973071

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Nontartrazine allergy with desipramine. Author(s): Hollander E. Source: The American Journal of Psychiatry. 1987 September; 144(9): 1247. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3631337

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Normal thyroid function in desipramine nonresponders converted to responders by the addition of L-triiodothyronine. Author(s): Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M. Source: The American Journal of Psychiatry. 1984 December; 141(12): 1614-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6439059

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On mixtures of three normal populations caused by monogenic inheritance: application to desipramine metabolism. Author(s): Miescke KJ, Musa MN. Source: Journal of Psychiatry & Neuroscience : Jpn. 1994 July; 19(4): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7918352

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Opioid peptides and receptors in relation to affective illness. Effects of desipramine and lithium on opioid receptors in rat brain. Author(s): Stengaard-Pedersen K, Schou M. Source: Acta Pharmacol Toxicol (Copenh). 1985; 56 Suppl 1: 170-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2984886

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Outcome with desipramine therapy in subtypes of nonpsychotic major depression. Author(s): Coryell W, Turner R. Source: Journal of Affective Disorders. 1985 September; 9(2): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2932488

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Overdosage of desipramine hydrochloride with marked electrocardiographic abnormalities. Author(s): Colvard C Jr. Source: Southern Medical Journal. 1968 November; 61(11): 1218 Passim. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5748406

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Paraphilias: a double-blind crossover comparison of clomipramine versus desipramine. Author(s): Kruesi MJ, Fine S, Valladares L, Phillips RA Jr, Rapoport JL. Source: Archives of Sexual Behavior. 1992 December; 21(6): 587-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1482282

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Patterns of plasma imipramine-desipramine concentrations in patients receiving concomitant fluphenazine decanoate. Author(s): Siris SG, Adan F, Lee A, Cooper TB, Mandeli J, Casey E. Source: The Journal of Clinical Psychiatry. 1988 February; 49(2): 64-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3338977

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Pediatric cardiovascular effects of imipramine and desipramine. Author(s): Bartels MG, Varley CK, Mitchell J, Stamm SJ. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1991 January; 30(1): 100-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2005043

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Personality traits and response to desipramine. Author(s): Peselow ED, Fieve RR, DiFiglia C. Source: Journal of Affective Disorders. 1992 April; 24(4): 209-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1578076

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Pharmacogenetics of desipramine metabolism. Author(s): Musa MN, Miescke KJ. Source: Int J Clin Pharmacol Ther. 1994 March; 32(3): 126-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8205373

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Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. Author(s): Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S. Source: Journal of Clinical Psychopharmacology. 1994 April; 14(2): 90-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8195463

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Pharmacokinetics of desipramine in Asian and Caucasian volunteers. Author(s): Pi EH, Tran-Johnson TK, Walker NR, Cooper TB, Suckow RF, Gray GE. Source: Psychopharmacology Bulletin. 1989; 25(3): 483-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2626521

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Phenobarbital induces the 2-hydroxylation of desipramine. Author(s): Spina E, Avenoso A, Campo GM, Caputi AP, Perucca E. Source: Therapeutic Drug Monitoring. 1996 February; 18(1): 60-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8848823

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Pilocarpine for anticholinergic adverse effects associated with desipramine treatment. Author(s): Salah RS, Cameron OG. Source: The American Journal of Psychiatry. 1996 April; 153(4): 579. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8599415

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Plasma desipramine levels and ECG changes in depressed young adults. Author(s): Barnhill JG. Source: Journal of Clinical Psychopharmacology. 1992 April; 12(2): 136-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1573037

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Platelet alpha 2-adrenergic receptors in depressed patients and healthy volunteers: the effects of desipramine. Author(s): Werstiuk ES, Auffarth SE, Coote M, Gupta RN, Steiner M. Source: Pharmacopsychiatry. 1992 July; 25(4): 199-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1326772

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Polymorphic 2-hydroxylation of desipramine. A population and family study. Author(s): Dahl ML, Iselius L, Alm C, Svensson JO, Lee D, Johansson I, IngelmanSundberg M, Sjoqvist F. Source: European Journal of Clinical Pharmacology. 1993; 44(5): 445-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8359181

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Post-stroke depression: combined treatment with imipramine or desipramine and mianserin. A controlled clinical study. Author(s): Lauritzen L, Bendsen BB, Vilmar T, Bendsen EB, Lunde M, Bech P. Source: Psychopharmacology. 1994 February; 114(1): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7846193

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Potential mechanism of desipramine-related sudden death in children. Author(s): Wagner KD, Fershtman M. Source: Psychosomatics. 1993 January-February; 34(1): 80-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8426895

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Potentially toxic serum concentrations of desipramine after discontinuation of valproic acid. Author(s): Joseph AB, Wroblewski BA. Source: Brain Injury : [bi]. 1993 September-October; 7(5): 463-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8401488

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Predicting desipramine levels in children and adolescents: a naturalistic clinical study. Author(s): Biederman J, Faraone SV, Baldessarini RJ, Flood J, Meyer M, Wilens T, Spencer T, Chen L, Weber W. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1997 March; 36(3): 384-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9055519

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Predictors of response to desipramine in dysthymia. Author(s): Friedman RA, Parides M, Baff R, Moran M, Kocsis JH. Source: Journal of Clinical Psychopharmacology. 1995 August; 15(4): 280-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7593711

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Preliminary report: placebo-controlled, double-blind study of the clinical and metabolic effects of desipramine in panic disorder. Author(s): Lydiard RB, Morton WA, Emmanuel NP, Zealberg JJ, Laraia MT, Stuart GW, O'Neil PM, Ballenger JC. Source: Psychopharmacology Bulletin. 1993; 29(2): 183-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8290663

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Premenstrual syndrome: a double-blind controlled trial of desipramine and methylscopolamine. Author(s): Taghavi E, Menkes DB, Howard RC, Mason PA, Shaw JP, Spears GF. Source: International Clinical Psychopharmacology. 1995 June; 10(2): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7673655

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Prior antidepressant treatment does not have an impact on response to desipramine treatment in major depression. Author(s): Young LT, Cooke RG, Levitt AJ, Joffe RT. Source: Biological Psychiatry. 1995 September 15; 38(6): 410-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8547462

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Quantification of imipramine and desipramine in plasma by high-performance liquid chromatography and fluorescence detection. Author(s): Reece PA, Zacest R, Barrow CG. Source: Journal of Chromatography. 1979 July 21; 163(3): 310-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=541386

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Quantitative determination of imipramine and desipramine in human blood plasma by direct densitometry of thin-layer chromatograms. Author(s): Nagy A, Treiber L. Source: The Journal of Pharmacy and Pharmacology. 1973 August; 25(8): 599-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4148426

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Quantitative gas chromatographic determination of nanogram levels of desipramine in serum. Author(s): Ervik M, Walle T, Ehrsson H. Source: Acta Pharm Suec. 1970 December; 7(6): 625-34. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5511714

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Quantitative homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine. Author(s): Pankey S, Collins C, Jaklitsch A, Izutsu A, Hu M, Pirio M, Singh P. Source: Clinical Chemistry. 1986 May; 32(5): 768-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3516450

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Quantitative mapping of metabolites of imipramine and desipramine in plasma samples by gas chromatographic-mass spectrometry. Author(s): Narasimhachari N, Saady J, Friedel RO. Source: Biological Psychiatry. 1981 October; 16(10): 937-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7306616

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Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine. Author(s): Brosen K, Gram LF. Source: European Journal of Clinical Pharmacology. 1989; 37(2): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2792169

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Raised serum levels of desipramine with the antiarrhythmic propafenone. Author(s): Katz MR. Source: The Journal of Clinical Psychiatry. 1991 October; 52(10): 432-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1938981

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Rapid cycling triggered by pindolol augmentation of paroxetine, but not with desipramine. Author(s): Kraus RP. Source: Depression. 1996; 4(2): 92-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9160648

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Rapid desipramine dose adjustment using 24-hour levels. Author(s): Nelson JC, Jatlow PI, Mazure C. Source: Journal of Clinical Psychopharmacology. 1987 April; 7(2): 72-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3584524

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Refractory depression: the addition of lithium to fluoxetine or desipramine. Author(s): Ontiveros A, Fontaine R, Elie R. Source: Acta Psychiatrica Scandinavica. 1991 March; 83(3): 188-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1903237

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Regulation of neurotransmitter receptors by desipramine and other antidepressant drugs: the neurotransmitter receptor hypothesis of antidepressant action. Author(s): Stahl SM. Source: The Journal of Clinical Psychiatry. 1984 October; 45(10 Pt 2): 37-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6090439

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Relapse to cocaine abuse after initiating desipramine treatment. Author(s): Weiss RD. Source: Jama : the Journal of the American Medical Association. 1988 November 4; 260(17): 2545-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3172429

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Relationship between desipramine plasma levels and the effect in Parkinson's syndrome. Author(s): Muscettola GB, Giovannucci M, Montanini R, Morselli PL, Garattini S. Source: Rev Eur Etud Clin Biol. 1972 April; 17(4): 375-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5079227

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Relationship between plasma desipramine levels and clinical outcome for RDC major depressive inpatients. Author(s): Simpson GM, Pi EH, Abdelmalek E, Boyd JL, Carroll RS, Cooper TB, Miller A. Source: Psychopharmacology. 1983; 80(3): 240-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6412268

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Relationship between plasma desipramine levels, CYP2D6 phenotype and clinical response to desipramine: a prospective study. Author(s): Spina E, Gitto C, Avenoso A, Campo GM, Caputi AP, Perucca E. Source: European Journal of Clinical Pharmacology. 1997; 51(5): 395-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9049581

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Relationship between tricyclic antidepressant plasma levels and clinical response in patients treated with desipramine or doxepin. Author(s): Brunswick DJ, Amsterdam JD, Potter L, Caroff S, Rickels K. Source: Acta Psychiatrica Scandinavica. 1983 June; 67(6): 371-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6880821

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Relationship of desipramine plasma levels to therapeutic response: a critical reappraisal of the data. Author(s): Friedel RO. Source: The Journal of Clinical Psychiatry. 1984 October; 45(10 Pt 2): 46-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6384208

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Research on desipramine in the treatment of cocaine abuse: a critique of Levin and Lehman's meta-analysis. Author(s): Delucchi KL. Source: Journal of Clinical Psychopharmacology. 1992 October; 12(5): 367-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1479061

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Reserpine augmentation of desipramine in refractory depression: clinical and neurobiological effects. Author(s): Price LH, Charney DS, Heninger GR. Source: Psychopharmacology. 1987; 92(4): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2442788

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Resolved: cardiac arrhythmias make desipramine an unacceptable choice in children. Author(s): Werry JS, Biederman J, Thisted R, Greenhill L, Ryan N. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1995 September; 34(9): 1239-45; Discussion 1245-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7559320

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Response of depression to very high plasma levels of imipramine plus desipramine. Author(s): Garvey M, DeRubeis RJ, Hollon SD, Evans MD, Tuason VB. Source: Biological Psychiatry. 1991 July 1; 30(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1892963

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Response to desipramine treatment in adolescent depression: a fixed-dose, placebocontrolled trial. Author(s): Kutcher S, Boulos C, Ward B, Marton P, Simeon J, Ferguson HB, Szalai J, Katic M, Roberts N, Dubois C, et al. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1994 June; 33(5): 686-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8056732

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Response to desipramine treatment in adolescent major depression. Author(s): Boulos C, Kutcher S, Marton P, Simeon J, Ferguson B, Roberts N. Source: Psychopharmacology Bulletin. 1991; 27(1): 59-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1862207

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Responses of growth hormone to desipramine in endogenous and non-endogenous depression. Author(s): Dinan TG, Barry S. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1990 May; 156: 680-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2095944

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Retreatment for relapse following desipramine discontinuation in dysthymia. Author(s): Friedman RA, Mitchell J, Kocsis JH. Source: The American Journal of Psychiatry. 1995 June; 152(6): 926-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7755126

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Role of imipramine & desipramine in counteracting diazepam induced changes of adenosinetriphosphatase & cholinesterase of human fetal brain. Author(s): Das S, Datta SC, Guin AK, Dey S, Sengupta D. Source: Indian J Exp Biol. 1981 August; 19(8): 738-43. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6458559

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Saliva and plasma desipramine levels in Asian and Caucasian volunteers. Author(s): Pi EH, Tran-Johnson TK, Gray GE, Walker NR, Suckow RF, Cooper TB. Source: Psychopharmacology Bulletin. 1991; 27(3): 281-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1775599

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Sertraline versus desipramine in the treatment of premenstrual syndrome: an openlabel trial. Author(s): Freeman EW, Rickels K, Sondheimer SJ, Wittmaack FM. Source: The Journal of Clinical Psychiatry. 1996 January; 57(1): 7-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8543554

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Serum haloperidol and desipramine concentrations and the treatment of psychotic depression: two case reports. Author(s): Lin KM, Poland RE, Fu P, Nuccio I, Lesser IM. Source: The Journal of Nervous and Mental Disease. 1989 July; 177(7): 431-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2746195

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Side effects of desipramine and age. Author(s): Galanter CA, Bilich C, Walsh BT. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Summer; 12(2): 13745. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12188982

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Side effects of methylphenidate and desipramine alone and in combination in children. Author(s): Pataki CS, Carlson GA, Kelly KL, Rapport MD, Biancaniello TM. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 September; 32(5): 1065-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8407753

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Simulation of acute myocardial infarction by desipramine hydrochloride. Author(s): Borganelli M, Forman MB. Source: American Heart Journal. 1990 June; 119(6): 1413-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2353627

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Simultaneous determination of imipramine and its metabolite desipramine in human plasma by capillary gas chromatography with mass-selective detection. Author(s): Pommier F, Sioufi A, Godbillon J. Source: J Chromatogr B Biomed Sci Appl. 1997 December 5; 703(1-2): 147-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9448071

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Simultaneous determination of imipramine, desipramine and their 2- and 10hydroxylated metabolites in human plasma and urine by high-performance liquid chromatography. Author(s): Chen AG, Wing YK, Chiu H, Lee S, Chen CN, Chan K. Source: J Chromatogr B Biomed Sci Appl. 1997 May 23; 693(1): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9200529

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Simultaneous determination of imipramine, desipramine and their deuteriumlabelled analogues in biological fluids by capillary gas chromatography-mass spectrometry. Author(s): Sasaki Y, Baba S. Source: Journal of Chromatography. 1988 April 8; 426(1): 93-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3384883

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Simultaneous determination of lofepramine and desipramine by a high-performance liquid chromatographic method used for therapeutic drug monitoring. Author(s): Elm T, Hansen EL. Source: Journal of Chromatography. B, Biomedical Applications. 1995 March 24; 665(2): 355-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7795815

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Simultaneous determination of viloxazine, venlafaxine, imipramine, desipramine, sertraline, and amoxapine in whole blood: comparison of two extraction/cleanup procedures for capillary gas chromatography with nitrogen-phosphorus detection. Author(s): Martinez MA, Sanchez de la Torre C, Almarza E. Source: Journal of Analytical Toxicology. 2002 July-August; 26(5): 296-302. Erratum In: J Anal Toxicol. 2003 March; 27(2): 8A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166817

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Simultaneous high-performance liquid chromatography-electrochemical detection determination of imipramine, desipramine, their 2-hydroxylated metabolites, and imipramine N-oxide in human plasma and urine: preliminary application to oxidation pharmacogenetics. Author(s): Koyama E, Kikuchi Y, Echizen H, Chiba K, Ishizaki T. Source: Therapeutic Drug Monitoring. 1993 June; 15(3): 224-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8333003

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Single and multiple desipramine exposures of cultured cells. Changes in cellular anisotropy and in lipid composition of whole cells and of plasma membranes. Author(s): Toplak H, Zuehlke R, Loidl S, Hermetter A, Honegger UE, Wiesmann UN. Source: Biochemical Pharmacology. 1990 May 1; 39(9): 1437-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2334444

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Six months of desipramine for dysthymia: can dysthymic patients achieve normal social functioning? Author(s): Friedman RA, Markowitz JC, Parides M, Gniwesch L, Kocsis JH. Source: Journal of Affective Disorders. 1999 August; 54(3): 283-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10467972

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Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Author(s): Wilens TE, Biederman J, Prince J, Spencer TJ, Faraone SV, Warburton R, Schleifer D, Harding M, Linehan C, Geller D. Source: The American Journal of Psychiatry. 1996 September; 153(9): 1147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8780417

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Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine. Author(s): Goodman WK, Price LH, Delgado PL, Palumbo J, Krystal JH, Nagy LM, Rasmussen SA, Heninger GR, Charney DS. Source: Archives of General Psychiatry. 1990 June; 47(6): 577-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2112374

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Steady-state plasma concentrations of imipramine and desipramine in relation to Smephenytoin 4'-hydroxylation status in Japanese depressive patients. Author(s): Koyama E, Tanaka T, Chiba K, Kawakatsu S, Morinobu S, Totsuka S, Ishizaki T. Source: Journal of Clinical Psychopharmacology. 1996 August; 16(4): 286-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835703

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Successful treatment of nonpurging bulimia nervosa with desipramine: a doubleblind, placebo-controlled study. Author(s): McCann UD, Agras WS. Source: The American Journal of Psychiatry. 1990 November; 147(11): 1509-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2221164

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Surface ionization organic mass spectrometry of imipramine, desipramine, clomipramine, and lidocaine. Author(s): Fujii T, Kurihara Y, Arimoto H, Mitsutsuka Y. Source: Analytical Chemistry. 1994 June 1; 66(11): 1884-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8030791

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Sympathetic nervous system activity in major depression. Basal and desipramineinduced alterations in plasma norepinephrine kinetics. Author(s): Veith RC, Lewis N, Linares OA, Barnes RF, Raskind MA, Villacres EC, Murburg MM, Ashleigh EA, Castillo S, Peskind ER, et al. Source: Archives of General Psychiatry. 1994 May; 51(5): 411-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8179465

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Temperament predicts clomipramine and desipramine response in major depression. Author(s): Joyce PR, Mulder RT, Cloninger CR. Source: Journal of Affective Disorders. 1994 January; 30(1): 35-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8151047

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Temporal factors in the enhancement of morphine analgesia by desipramine. Author(s): Gordon NC, Heller PH, Gear RW, Levine JD. Source: Pain. 1993 June; 53(3): 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8351157

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The effect of carbamazepine on the 2-hydroxylation of desipramine. Author(s): Spina E, Avenoso A, Campo GM, Caputi AP, Perucca E. Source: Psychopharmacology. 1995 February; 117(4): 413-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7604141

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The effect of chronic oral desipramine on capsaicin-induced allodynia and hyperalgesia: a double-blinded, placebo-controlled, crossover study. Author(s): Wallace MS, Barger D, Schulteis G. Source: Anesthesia and Analgesia. 2002 October; 95(4): 973-8, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12351279

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The effect of desipramine on basal and naloxone-stimulated cortisol secretion in humans: interaction of two drugs acting on noradrenergic control of adrenocorticotropin secretion. Author(s): Torpy DJ, Grice JE, Hockings GI, Crosbie GV, Walters MM, Jackson RV. Source: The Journal of Clinical Endocrinology and Metabolism. 1995 March; 80(3): 802-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7883833

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The effect of sertraline on the pharmacokinetics of desipramine and imipramine. Author(s): Kurtz DL, Bergstrom RF, Goldberg MJ, Cerimele BJ. Source: Clinical Pharmacology and Therapeutics. 1997 August; 62(2): 145-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9284850

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The human desipramine-sensitive noradrenaline transporter and the importance of defined amino acids for its function. Author(s): Bonisch H, Runkel F, Roubert C, Giros B, Bruss M. Source: Journal of Autonomic Pharmacology. 1999 December; 19(6): 327-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961738

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The influence of the route of administration of imipramine on imipramine and desipramine blood levels. Author(s): Rigal J, Albin H, Fanca X, Demotes-Mainard F, Vincon G. Source: Journal of Clinical Psychopharmacology. 1989 October; 9(5): 364-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2677063

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The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function. Author(s): Zhu MY, Kyle PB, Hume AS, Ordway GA. Source: Neurochemical Research. 2004 February; 29(2): 419-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15002740

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The safety of desipramine. Author(s): Werry JS. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1994 May; 33(4): 588-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8005913

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The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine, improves memory performance during acute major depression. Author(s): Levkovitz Y, Caftori R, Avital A, Richter-Levin G. Source: Brain Research Bulletin. 2002 August 15; 58(4): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12183009

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The thyroid axis and desipramine treatment in depression. Author(s): Brady KT, Anton RF. Source: Biological Psychiatry. 1989 March 15; 25(6): 703-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2493818

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The toxicity and dose of desipramine hydrochloride. Author(s): Amitai Y, Frischer H. Source: Jama : the Journal of the American Medical Association. 1994 December 14; 272(22): 1719-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7966907

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The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine. Author(s): Singer HS, Brown J, Quaskey S, Rosenberg LA, Mellits ED, Denckla MB. Source: Pediatrics. 1995 January; 95(1): 74-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7770313

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The tricyclic antidepressant desipramine causes proteolytic degradation of lysosomal sphingomyelinase in human fibroblasts. Author(s): Hurwitz R, Ferlinz K, Sandhoff K. Source: Biol Chem Hoppe Seyler. 1994 July; 375(7): 447-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7945993

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Therapeutic effects of imipramine are counteracted by its metabolite, desipramine, in patients with generalized anxiety disorder. Author(s): McLeod DR, Hoehn-Saric R, Porges SW, Kowalski PA, Clark CM. Source: Journal of Clinical Psychopharmacology. 2000 December; 20(6): 615-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106132

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Treatment of cocaine dependence in methadone maintenance clients: a pilot study comparing the efficacy of desipramine and amantadine. Author(s): Kolar AF, Brown BS, Weddington WW, Haertzen CC, Michaelson BS, Jaffe JH. Source: Int J Addict. 1992; 27(7): 849-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1319961

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Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison. Author(s): Leonard HL, Swedo SE, Rapoport JL, Koby EV, Lenane MC, Cheslow DL, Hamburger SD. Source: Archives of General Psychiatry. 1989 December; 46(12): 1088-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2686576

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Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine. Author(s): Babaliaros VC, Hurst JW. Source: Clin Cardiol. 2002 August; 25(8): 395-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173907

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Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Author(s): Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, Moreno FA, Heninger GR, Charney DS. Source: Biological Psychiatry. 1999 July 15; 46(2): 212-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10418696

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Urinary desipramine hydroxylation index and steady-state plasma concentrations of imipramine and desipramine. Author(s): Spina E, Arena A, Pisani F. Source: Therapeutic Drug Monitoring. 1987 June; 9(2): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3617150

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Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards. Author(s): Veith RC, Bielski RJ, Bloom V, Fawcett JA, Narasimhachari N, Friedel RO. Source: Journal of Clinical Psychopharmacology. 1983 February; 3(1): 18-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6833519

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Use of desipramine in depressed inpatients. Author(s): Nelson JC. Source: The Journal of Clinical Psychiatry. 1984 October; 45(10 Pt 2): 10-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6384205

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Use of desipramine in the medically ill. Author(s): Cavanaugh SV. Source: The Journal of Clinical Psychiatry. 1984 October; 45(10 Pt 2): 23-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6480574

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Usefulness of single plasma desipramine levels. Author(s): Brunswick DJ, Cooper TB. Source: Journal of Clinical Psychopharmacology. 1983 February; 3(1): 57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6833526

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Utility of crossover designs in clinical trials: efficacy of desipramine vs. placebo in opioid-dependent cocaine abusers. Author(s): Feingold A, Oliveto A, Schottenfeld R, Kosten TR. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Spring; 11(2): 111-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028741

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Value of the DST for predicting response of patients with major depression to hospitalization and desipramine. Author(s): Nelson JC, Mazure CM, Jatlow PI. Source: The American Journal of Psychiatry. 1990 November; 147(11): 1488-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2221161

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Variant ventricular tachycardia in desipramine toxicity. Author(s): Lee WR, Sheikh MU, Covarrubias EA, Slotkoff LM. Source: Southern Medical Journal. 1981 October; 74(10): 1268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7292072

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Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2. Author(s): Ball SE, Ahern D, Scatina J, Kao J. Source: British Journal of Clinical Pharmacology. 1997 June; 43(6): 619-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9205822

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Ventricular tachycardia associated with desipramine and thioridazine. Author(s): Wilens TE, Stern TA. Source: Psychosomatics. 1990 Winter; 31(1): 100-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2300645

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What desipramine plasma levels are therapeutic? Author(s): Boyer WF, Lake CR. Source: Journal of Clinical Psychopharmacology. 1984 April; 4(2): 118-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6707240

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Withdrawal from chronic phencyclidine (PCP) dependence with desipramine. Author(s): Tennant FS Jr, Rawson RA, McCann M. Source: The American Journal of Psychiatry. 1981 June; 138(6): 845-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7246821

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Withdrawal from long-term high-dose desipramine therapy. Clinical and biological changes. Author(s): Brown GM, Stancer HC, Moldofsky H, Harman J, Murphy JT, Gupta RN. Source: Archives of General Psychiatry. 1978 October; 35(10): 1261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=211986

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CHAPTER 2. NUTRITION AND DESIPRAMINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and desipramine.

Finding Nutrition Studies on Desipramine 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 “desipramine” (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 “desipramine” (or a synonym): •

Cyclic AMP and inositol phosphate accumulations in rat brain cortical slices following chronic citalopram or desipramine administration. Author(s): Department of Pharmacology, Faculty of Medicine of Paris XII, Creteil, France. Source: Sapena, R Morin, D Zini, R Tillement, J P Drugs-Exp-Clin-Res. 1994; 20(3): 93102 0378-6501

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Different effect of desipramine on locomotor activity in quinpirole-treated rats after repeated restraint and chronic mild stress. Author(s): Dipartimento di Scienze del Farmaco, Universita degli Studi di Sassari, Italy. [email protected] Source: D'Aquila, P S Peana, A T Carboni, V Serra, G J-Psychopharmacol. 2000; 14(4): 347-52 0269-8811

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Effects of yohimbine and desipramine on adrenal catecholamine release in response to splanchnic nerve stimulation in anesthetized dogs. Author(s): Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Sendai, Japan. Source: Koganei, H Takeuchi, A Kimura, T Satoh, S Biol-Pharm-Bull. 1995 September; 18(9): 1207-10 0918-6158

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Inhibition of desipramine 2-hydroxylation by quinidine and quinine in rapid and slow debrisoquine hydroxylators. Author(s): Institute of Pharmacology, University of Messina, Italy. Source: Spina, E Steiner, E Dumont, E Dahlqvist, R Psychopharmacol-Ser. 1989; 7201-5 0931-6795

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Long-term in vivo desipramine or estrogen treatment fails to affect serotonin-induced outward current in hippocampal pyramidal cells of the rat. Author(s): Department of Neuropharmacology, Organon International RE2140, Oss, The Netherlands. Source: Dijcks, F A Couvee, J H Ruigt, G S Neuroscience. 1994 May; 60(1): 213-25 03064522

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Olfactory bulbectomy provokes a suppression of interleukin-1beta and tumour necrosis factor-alpha production in response to an in vivo challenge with lipopolysaccharide: effect of chronic desipramine treatment. Author(s): Department of Pharmacology, National University of Ireland, Galway, Ireland. [email protected] Source: Connor, T J Harkin, A Kelly, J P Leonard, B E Neuroimmunomodulation. 2000; 7(1): 27-35 1021-7401

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Preclinical evaluation of the effects of buprenorphine, naltrexone and desipramine on cocaine self-administration. Author(s): McLean Hospital-Harvard Medical School, Alcohol and Drug Abuse Research Center, Belmont, MA 02178. Source: Mello, N K NIDA-Res-Monogr. 1991; 105189-95 1046-9516

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Rauwolscine potentiates the effect of desipramine on limbic noradrenaline efflux. Author(s): Anaesthetics Unit (Neurotransmission Laboratory), London Hospital Medical College, Whitechapel, UK. Source: Palij, P Stamford, J A Neuroreport. 1996 April 26; 7(6): 1121-4 0959-4965

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Repeated administration of fluoxetine, desipramine and tranylcypromine increases dopamine D2-like but not D1-like receptor function in the rat. Author(s): University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, UK. Source: Ainsworth, K Smith, S E Sharp, T J-Psychopharmacol. 1998; 12(3): 252-7 02698811

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The effect of cocaine and desipramine on neuronal uptake of [3H]-noradrenaline and sensitivity to noradrenaline of rat mesenteric resistance arteries. Author(s): Department of Medicine, University of Manchester, UK. Source: Byg, A M Bund, S Mulvany, M J Aalkjaer, C Clin-Exp-Pharmacol-Physiol. 1994 August; 21(8): 623-30 0305-1870

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Trypanocidal resistance in Trypanosoma evansi in vitro: effects of verapamil, cyproheptidine, desipramine and chlorpromazine alone and in combination with trypanocides. Author(s): Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Nigeria. Source: Anene, B M Ross, C A Anika, S M Chukwu, C C Vet-Parasitol. 1996 March; 62(12): 43-50 0304-4017

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

•

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/

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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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WebMDHealth: 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 desipramine; 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 Alternative names: Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com

•

Minerals Alpha-Tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Beta-Tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com D-Alpha-Tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Delta-Tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Gamma-Tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND DESIPRAMINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to desipramine. 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 desipramine 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 “desipramine” (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 desipramine: •

1-Methyl-4-phenylpyridinium accumulates in cerebellar granule neurons via organic cation transporter 3. Author(s): Shang T, Uihlein AV, Van Asten J, Kalyanaraman B, Hillard CJ. Source: Journal of Neurochemistry. 2003 April; 85(2): 358-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12675912

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A possible mechanism of antidepressant activity of beta-amyrin palmitate isolated from Lobelia inflata leaves in the forced swimming test. Author(s): Subarnas A, Tadano T, Nakahata N, Arai Y, Kinemuchi H, Oshima Y, Kisara K, Ohizumi Y. Source: Life Sciences. 1993; 52(3): 289-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8423710

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Adhesion of human blood platelets to glass and polymer surfaces. I. Studies with platelets in plasma. Author(s): Mohammad SF, Hardison MD, Glenn CH, Morton BD, Bolan JC, Mason RG. Source: Haemostasis. 1974; 3(5-6): 257-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4219776

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Affinity and specificity of N-methyl- D-aspartate channel blockers affect their ability to disrupt prepulse inhibition of acoustic startle in rats. Author(s): Wiley JL, Harvey SA, Balster RL, Nicholson KL. Source: Psychopharmacology. 2003 February; 165(4): 378-85. Epub 2002 November 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459931

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Agastache mexicana may produce anxiogenic-like actions in the male rat. Author(s): Molina-Hernandez M, Tellez-Alcantara P, Martinez E. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2000 June; 7(3): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185730

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Amine uptake inhibition by diosmin and diosmetin in human neuronal and neuroendocrine cell lines. Author(s): Sher E, Codignola A, Biancardi E, Cova D, Clementi F. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 1992 December; 26(4): 395-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1338224

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Anticonvulsant drugs and the genetically epilepsy-prone rat. Author(s): Dailey JW, Jobe PC. Source: Fed Proc. 1985 July; 44(10): 2640-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3924665

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Anxiolytic-like actions of leaves of Casimiroa edulis (Rutaceae) in male Wistar rats. Author(s): Molina-Hernandez M, Tellez-Alcantara NP, Perez Garcia J, Lopez JI, Jaramillo MT. Source: Journal of Ethnopharmacology. 2004 July; 93(1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15182911

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Behavioral evidence implicating dopamine in sensorimotor arousal and norepinephrine in the sedative effects of antidepressant drugs. Author(s): Kokkinidis L, McCarter BD. Source: Psychopharmacology. 1990; 100(4): 542-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2320716

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Bradykinin B2-receptor-mediated stimulation of exocytotic noradrenaline release from cardiac sympathetic neurons. Author(s): Kurz T, Tolg R, Richardt G. Source: Journal of Molecular and Cellular Cardiology. 1997 September; 29(9): 2561-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9299378

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Cardiovascular effects of cocaine in humans: laboratory studies. Author(s): Foltin RW, Fischman MW, Levin FR. Source: Drug and Alcohol Dependence. 1995 March; 37(3): 193-210. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7796714

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Complications of vesicoureteral operations from incoordination of micturition. Author(s): Hinman F Jr, Baumann FW. Source: The Journal of Urology. 1976 November; 116(5): 638-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=978818

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Contribution of flavin-containing monooxygenase and cytochrome P450 to imipramine N-oxidation in rat hepatic microsomes. Author(s): Narimatsu S, Yamamoto S, Kato R, Masubuchi Y, Horie T. Source: Biological & Pharmaceutical Bulletin. 1999 June; 22(6): 567-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408227

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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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Demographics, assessment and management of pain in the elderly. Author(s): Davis MP, Srivastava M. Source: Drugs & Aging. 2003; 20(1): 23-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12513114

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Diabetic neuropathy: an intensive review. Author(s): Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2004 January 15; 61(2): 160-73; Quiz 175-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750401

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Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity? Author(s): Ouagazzal AM, Jenck F, Moreau JL.

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Source: Psychopharmacology. 2001 July; 156(2-3): 273-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549229 •

Early postnatal deprivation of active sleep with desipramine or zimeldine impairs later behavioural reactivity to auditory stimuli in rats. Author(s): Hilakivi LA, Taira T, Hilakivi I. Source: Acta Physiologica Scandinavica. 1988 February; 132(2): 191-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2976228

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Effect of desmethylimipramine on norepinephrine content and plasticity of kitten visual cortex. Author(s): Allen EE, Blakemore LJ, Trombley PQ, Gordon B. Source: Brain Research. 1987 January 20; 401(2): 397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3101982

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Effect of Ocimum sanctum roots extract on swimming performance in mice. Author(s): Maity TK, Mandal SC, Saha BP, Pal M. Source: Phytotherapy Research : Ptr. 2000 March; 14(2): 120-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10685110

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Effectiveness of adjunct therapies in crack cocaine treatment. Author(s): Richard AJ, Montoya ID, Nelson R, Spence RT. Source: Journal of Substance Abuse Treatment. 1995 November-December; 12(6): 401-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749724

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Effects of an extract of Ginkgo biloba on rabbit isolated aorta. Author(s): Auguet M, DeFeudis FV, Clostre F, Deghenghi R. Source: General Pharmacology. 1982; 13(3): 225-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7095401

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Effects of dietary gamma-linolenic acid and prenatal ethanol on mouse brain and behavior. Author(s): Wainwright PE, Huang YS, Levesque S, Mutsaers L, McCutcheon D, Balcaen P, Hammond J. Source: Pharmacology, Biochemistry, and Behavior. 1996 April; 53(4): 843-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8801587

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Effects of Hypericum perforatum (St. John's wort) on passive avoidance in the rat: evaluation of potential neurochemical mechanisms underlying its antidepressant activity. Author(s): Misane I, Ogren SO.

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Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S89-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518084 •

Effects of pharmacological agents on the physiological responses of hair discs. Author(s): Smith KR Jr, Creech BJ. Source: Experimental Neurology. 1967 December; 19(4): 477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4294914

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Effects of tricyclic antidepressant drugs on the electrophysiological properties of drug Purkinje fibers. Author(s): Muir WW, Strauch SM, Schaal SF. Source: Journal of Cardiovascular Pharmacology. 1982 January-February; 4(1): 82-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6176805

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Effects of vinblastine on catecholamine-biosynthetic enzymes in heart, sympathetic ganglion and adrenal glands of rats. Author(s): Hanbauer I, Kopin IJ, Maengwyn-Davies GD, Thoa NB, Weise VK. Source: British Journal of Pharmacology. 1973 May; 48(1): 106-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4146761

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Electrocortical changes in the encephale isole cat following chronic treatment with antidepressant drugs. Author(s): Neal H, Bradley PB. Source: Neuropharmacology. 1979 July; 18(7): 611-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=492483

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Enzymatic and chemical demethylenation of (methylenedioxy)amphetamine and (methylenedioxy)methamphetamine by rat brain microsomes. Author(s): Lin LY, Kumagai Y, Cho AK. Source: Chemical Research in Toxicology. 1992 May-June; 5(3): 401-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1354504

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Evaluation and clinical management of cocaine abusers. Author(s): Millman RB. Source: The Journal of Clinical Psychiatry. 1988 February; 49 Suppl: 27-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3276671

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Fear-enhanced acoustic startle is not attenuated by acute or chronic imipramine treatment in rats. Author(s): Cassella JV, Davis M.

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Source: Psychopharmacology. 1985; 87(3): 278-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3936082 •

Imipramine poisoning in a child: lack of efficacy of resin hemoperfusion. Author(s): Ryan R 3rd, Wians FH Jr, Stigelman WH Jr, Clark H, McCurdy F. Source: Pediatric Emergency Care. 1985 December; 1(4): 201-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3842167

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In vitro activity of mitochondrial ATP synthetase inhibitors against Plasmodium falciparum. Author(s): Basco LK, Le Bras J. Source: The Journal of Eukaryotic Microbiology. 1994 May-June; 41(3): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8049680

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Influence of some drugs on chlorpromazine-induced adrenaline release. Author(s): Vapaatalo HI. Source: Ann Med Exp Biol Fenn. 1968; 46(2): 226-32. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4389982

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Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug resistance. Author(s): Jaffrezou JP, Chen G, Duran GE, Muller C, Bordier C, Laurent G, Sikic BI, Levade T. Source: Biochimica Et Biophysica Acta. 1995 April 6; 1266(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7718613

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Inhibition of the oligosaccharides extracted from Morinda officinalis, a Chinese traditional herbal medicine, on the corticosterone induced apoptosis in PC12 cells. Author(s): Li YF, Gong ZH, Yang M, Zhao YM, Luo ZP. Source: Life Sciences. 2003 January 10; 72(8): 933-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493574

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Inhibition of vesicular uptake of monoamines by hyperforin. Author(s): Roz N, Mazur Y, Hirshfeld A, Rehavi M. Source: Life Sciences. 2002 September 27; 71(19): 2227-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12215370

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Interaction of triazolam with desipramine. Effects of single and repeated treatment on certain pharmacologic responses and brain catecholamine levels. Author(s): Kusaka M, Horikawa A, Meshi T, Maruyama Y.

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Source: Psychopharmacology. 1980; 70(3): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6108590 •

Interactions of tricyclic antidepressants and barbiturates in barbiturate-tolerant and nontolerant rats. Author(s): Liu SJ, Huang CL, Waters IW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1975 August; 194(2): 285-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1151759

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Intraventricular insulin suppresses the acoustic startle response in rats. Author(s): Thompson SC, Woods SC, Hendricks S, Bell SM, Figlewicz DP. Source: Physiology & Behavior. 2000 June 1-15; 69(4-5): 433-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10913781

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Involvement of GABAergic systems in manifestation of pharmacological activity of desipramine. Author(s): Asahi Y, Yonehara N. Source: Japanese Journal of Pharmacology. 2001 July; 86(3): 316-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488432

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Lack of association between thyroid and pineal responses to antidepressant treatment. Author(s): Brown GM, Singer W, Joffe R. Source: Depression. 1996; 4(2): 73-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9160644

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Low dose desipramine treatment of cocaine-related panic attacks. Author(s): Bystritsky A, Ackerman DL, Pasnau RO. Source: The Journal of Nervous and Mental Disease. 1991 December; 179(12): 755-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1744635

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Lysosomal physiology in Tetrahymena. 3. Pharmacological studies on acid hydrolase release and the ingestion and egestion of dimethylbenzanthracene particles. Author(s): Rothstein TL, Blum JJ. Source: The Journal of Cell Biology. 1974 September; 62(3): 844-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4152946

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Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission. Author(s): L'Heureux R, Dennis T, Curet O, Scatton B.

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Source: Journal of Neurochemistry. 1986 June; 46(6): 1794-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2871129 •

Mesolimbic noradrenaline but not dopamine is responsible for organization of rat behavior in the forced swim test and an anti-immobilizing effect of desipramine. Author(s): Plaznik A, Danysz W, Kostowski W. Source: Pol J Pharmacol Pharm. 1985 May-June; 37(3): 347-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3934653

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Psychogenic aspects of dermatology: a clinical trial of Norpramin. Author(s): Ede M. Source: Psychosomatics. 1965 September-October; 6(5): 376-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5319253

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/

•

HealthGate: http://www.tnp.com/

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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The following is a specific Web list relating to desipramine; 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 Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Integrative Medicine Communications; www.drkoop.com Eating Disorders Source: Healthnotes, Inc.; www.healthnotes.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Tricyclic Antidepressants (TCAs) Source: Integrative Medicine Communications; www.drkoop.com Yohimbe Source: Prima Communications, Inc.www.personalhealthzone.com

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.

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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. PATENTS ON DESIPRAMINE 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 “desipramine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on desipramine, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Desipramine By performing a patent search focusing on desipramine, 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 desipramine: •

Despiramine in the treatment of drug-resistant malarial infections Inventor(s): Bitonti; Alan J. (Maineville, OH), McCann; Peter P. (Lenexa, KS), Sjoerdsma; Albert (Cincinnati, OH) Assignee(s): Merrell Dow Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 5,373,005 Date filed: March 5, 1993 Abstract: Drug-resistant malarial infection in humans can be effectively treated with standard antimalarial agents if administered in conjunction with desipramine. Excerpt(s): This invention relates to the use of desipramine in the treatment of drugresistant Plasmodium infections. Malaria remains a significant health threat to humans despite massive international attempts to eradicate the disease. Over 200 million people are said to have malaria and over one million deaths per year are associated with malaria in Africa alone. In many of the endemic areas, local supply of food is quite limited, a problem which is greatly aggravated by the presence of protozoal infections in cattle and other farm animals. Malaria is a disease of warm blooded animals caused by infection with a parasite of the genus Plasmodium. Four species, P. vivax, P. falciparum, P. malariae, and P. ovale, are known to infect humans. The parasite is transmitted to humans by the bite of Anopheles mosquitoes. Subsequent to mosquito bite, the parasite rapidly invades the blood cells of the victim and after a incubation period, generally lasting about 10 to 14 days, symptoms, consisting of chills, fever, headache, muscle pains, splenomegaly, and anemia, appear. This incubation period may be prolonged for many weeks and onset can be quite insidious. Red blood cells are at first altered and later destroyed by the infection. Drug therapy utilizing quinine, chloroquine, amodiaquine, primaquine, and other agents has been the mainstay of therapy against malaria. However, drug-resistant strains of plasmodia have developed and in some cases strains are resistant to many or all of the current therapeutic agents. In particular, P. falciparum malaria is quite prone to exhibit single and even multiple drug-resistance. While new agents are continually developed and introduced, resistance to such new agents also quickly develops. For example mefloquine-resistant malaria was reported even before mefloquine licensure was completed. There is, thus, an urgent need for antimalarial agents which can be used in the treatment of drug-resistant malarial diseases. Web site: http://www.delphion.com/details?pn=US05373005__

•

Methods and compositions for treating attention-deficit/hyperactivity disorder Inventor(s): Paul; Julie Chasen (2010 Centennial Ct., Ballwin, MO 63011), Tenenbaum; Steven Joseph (384 Littany La., Chesterfield, MO 63017) Assignee(s): none reported Patent Number: 5,719,178 Date filed: November 20, 1995

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Abstract: A regimen and composition for treating Attention Deficit/Hperactivity Disorder (ADHD) by the use of proanthocyanidin both with and without a heterocyclic anti-depresssant, preferably desipramine and a citrus bioflavinoid. Excerpt(s): The invention relates to the treatment of Attention Deficit/Hyperactivity Disorder ("ADHD") generally and specifically methods and compositions for treating ADHD by use of proanthocyanidin in a controlled regimen both with and without a heterocyclic antidepressant, preferably desipramine and a citrus bioflavinoid. The predominantly Hyperactive-impulsive subtype is characterized by fidgetiness, excessive unproductive movement when inappropriate such as fidgeting with objects, tapping hands, shaking legs or feet, excessive talking or making noise. Symptoms in adults or adolescents frequently take the form of feelings of restlessness and difficulty in engaging in quiet sedentary activities. On the other hand, impulsivity manifests itself as impatience, difficulty in delaying responses, blurting out answers before questions have been completed, difficulty awaiting one's turn, frequently interrupting or intruding on others, making comments out of turn, failing to listen to directions, initiating conversations at inappropriate times, grabbing objects form others, touching things they are not supposed to touch and clowning around. Web site: http://www.delphion.com/details?pn=US05719178__

Patent Applications on Desipramine 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 desipramine: •

Method for treating tension-type headache Inventor(s): Bendtsen, Lars; (Slagelse, DK), Jensen, Rigmor; (Virum, DK), Madsen, Ulf; (Horsholm, DK), Olesen, Jes; (Hellerup, DK) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, N.W.; Washington; DC; 20001; US Patent Application Number: 20020072543 Date filed: August 30, 2001 Abstract: Tension-type headache is treated by interacting smith neuronal transmission in relation to pain in connection with headache in a way which prevents or decreases sensitization of second order nociceptive neurons. In particular, treatment is performed by administration of an effective amount of a substance which prevents or decreases central sensitization. Important examples of such substances are substances which interact with glutamate neurotransmission, such as glutamate receptor antagonists, such as NMDA receptor antagonists, such as MK-801 or Amitriptylline or Imipramine or Desipramine or Mirtazaprine or Venlafaxine. Other examples are substances which interact with nitric oxide, such as nitric oxide synthase (NOS) inhibitors, such as LNMMA or L-NAME or L-NIO or L-NNA. According to a broader aspect of the invention tension-type headache is treated by administration of substances which are effective in preventing or decreasing pain in connection with tension-type headache,

9

This has been a common practice outside the United States prior to December 2000.

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such as the substances mentioned above. An additional aspect of the invention relates to treatment of tension-type headache by administration of substances which substantially inhibit the activity of nitric oxide synthase (NOS), such as NOS inhibitors, such as LNMMA or L-NAME or L-NIO or L-NNA. Excerpt(s): This application is a nonprovisional claiming the benefit under 35 USC.sctn.119(e) of provisional Serial No. 06/085,413, filed May 14, 1998. This application is also a continuation-in-part of PCT/DK97/00502, filed Nov. 4, 1997, a PCT application designating the United States, which is a nonprovisional claiming the benefit under 35 USC.sctn.19(e) of provisional Serial No. 06/030,292, filed Nov. 5, 1996. All of the above applications are hereby incorporated by reference in their entirety. Previously, headache disorders were not clearly distinguished and it was widely believed that they formed part of a continuum and were strongly related. In 1988, The International Headache Society, (IHS) via its ad hoc committee on classification published a document entitled Classification and Diagnostic Criteria for Headache Disorders, Cranial Neuralgias and Facial Pain (Classification and Diagnostic Criteria for Headache Disorders, 1988). A new entity was here defined by name of tension-type headache. This entity was practically the same as conditions previously called tension headache, muscle contraction headache, psycho-myogenic headache and idiopathic headache. The IHS classification also defined a number of other specific headache diseases. Today it therefore gives no meaning to talk about headache in general. It would be the same as to discuss bellyache and chest pain without specifying its type and etiology. Due to the development in diagnostic accuracy research results obtained before 1988 have uncertain validity. Tension-type headache was subdivided by the IHS Classification Committee into an episodic form occurring less than half of all days and a chronic form occurring half of all days or more. Furthermore, both of these divisions were further subdivided into a form with disorder of pericranial muscle and a form without such disorder. It is thus crucial that research and patents specify which of the subforms are included. 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 desipramine, 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 “desipramine” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on desipramine. You can also use this procedure to view pending patent applications concerning desipramine. 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 5. BOOKS ON DESIPRAMINE Overview This chapter provides bibliographic book references relating to desipramine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on desipramine 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 Desipramine In order to find chapters that specifically relate to desipramine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and desipramine 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 “desipramine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on desipramine: •

Other Medicines for ADHD Source: in Barkley, R.A. Taking Charge of ADHD: The Complete, Authoritative Guide for Parents. New York, NY: Guilford Press. 2000. p. 288-293. Contact: Available from Guilford Publications. 72 Spring Street, New York, NY 10012. (800) 365-7006. Fax (212) 966-6708. E-mail: [email protected]. Website: www.guilford.com. PRICE: $18.95 plus shipping and handling. ISBN: 1572305606. Summary: Children whose problems with attention, overactivity, and lack of inhibition reach a certain level have a developmental disability known as attention deficit hyperactivity disorder (ADHD). This chapter on medications (drug therapy) is from a book intended to help parents who are raising a child with ADHD and for others who wish to know more about the disorder and its management. The author's main goal is to empower parents to take charge of the care of these often demanding children in a way that ensures the health of the entire family, collectively and individually. In this chapter, the author focuses on drugs other than stimulants, the drugs most commonly used.

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Although they are not as effective as the stimulants, several drugs called antidepressants and a drug called clonidine, used to treat high blood pressure, can be of some benefit to those with ADHD. The author reviews the tricyclic antidepressants, including Norpramin or Pertofrane (desipramine), Tofranil (imipramine), and Elavil (amitriptyline), covering side effects, drug interactions, and how these drugs are used with children. The author then discusses Wellbutrin (buproprion hydrochloride), and clonidine (usually marketed under its generic name), including side effects and how these drugs are used with children. •

Effective Therapies Source: in Manu, P. Pharmacotherapy of Common Functional Syndromes: EvidenceBased Guidelines for Primary Care Practice. Binghamton, NY: Haworth Medical Press. 2000. p. 125-130. Contact: Available from Haworth Medical Press, an imprint of Haworth Press, Inc. 10 Alice Street, Binghamton, New York 13904-1580. (800) HAWORTH or (800) 429-6784. Outside United States and Canada (607) 722-5857. Fax (800) 895-0582. E-mail: [email protected]. Website: www.haworthpressinc.com. PRICE: $69.95 plus shipping and handling. ISBN: 0789005883. Summary: This chapter is from a book that evaluates drug therapies for each of the four major functional disorders: chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome (IBS), and premenstrual syndrome. In this chapter, the second of six short chapters that focus on IBS, the author introduces and reviews the effective therapies for the condition. The author focuses on the tricyclic antidepressants, notably amitriptyline, trimipramine, and desipramine. The author discusses some of the basic research on each drug's use in patients with IBS. Amitriptyline improved the symptoms of 79 percent of the patients studied. The improvement reached a highly significant level when baseline symptoms were compared to the status immediately following the administration of the tricyclic drug. Amitriptyline induced improvement was more frequently observed among patients whose IBS was of moderate severity and among those whose baseline evaluation indicated high depression and anxiety scores. Compared with placebo, treatment with trimipramine significantly reduced the severity of vomiting, sleeplessness, and depression, as well as the presence of mucus in stool. However, for the other six target symptoms, including the main complaint of abdominal pain, the frequency and severity was reduced to a similar degree in both the placebo and trimipramine groups. Closely related to trimipramine, desipramine resulted in improvement in 54 percent of the patients in one study reported. The diarrhea predominant cases were more likely to respond to desipramine (68 percent) than the constipation predominant subgroup (22 percent).

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CHAPTER 6. PERIODICALS AND NEWS ON DESIPRAMINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover desipramine.

News Services and Press Releases One of the simplest ways of tracking press releases on desipramine 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 “desipramine” (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 desipramine. 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 “desipramine” (or synonyms). The following was recently listed in this archive for desipramine: •

Sertraline superior to desipramine for treatment of depression plus OCD Source: Reuters Medical News Date: January 21, 2000

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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 “desipramine” (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 “desipramine” (or synonyms). If you know the name of a company that is relevant to desipramine, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “desipramine” (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

Periodicals and News

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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 “desipramine” (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 desipramine: •

Antidepressants and Functional Gastrointestinal Disorders Source: Participate. 9(4): 1-3. Winter 2000. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. Summary: Antidepressants are commonly prescribed for the treatment of functional gastrointestinal (GI) disorders; they are unique drugs that have a number of properties that make them particularly useful. This article reviews three factors regarding antidepressants and functional GI disorders. The first is the mechanism of action of antidepressants, or how they exert their effect. The second is the relationship between the brain and the gut, also known as the 'brain gut axis.' Finally is the role of antidepressants in treating the various symptoms of functional GI disorders. The author first offers a history of the development of antidepressant drugs and their use for GI disorders, notably irritable bowel syndrome (IBS) and noncardiac chest pain (NCCP). Patients with IBS treated with the tricyclic desipramine (Norpramin) demonstrated improvement in their GI symptoms as well as a better sense of overall well being. Patients with NCCP on imipramine (Tofranil) reported a significant improvement in their gastrointestinal symptoms as well as improvement in their overall sense of well being. The author concludes with a brief discussion of the biopsychosocial model, where multiple dimensions of the patient's life, including gut function, overall well being, overall quality of life, and emotional status, are considered in patient treatment strategies. The use of dietary modification, antispasmodics, antidiarrheals, antidepressants, and behavioral interventions such as biofeedback, psychotherapy, and relaxation therapy all play a synergistic and important role in improving outcomes in functional gastrointestinal disorders. The author also stresses the importance of adequate patient education and patients participating as active members of their own health care team. One sidebar discusses the use of drugs based on serotonin for treating IBS.

Academic Periodicals covering Desipramine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to desipramine. In addition to these sources, you can search for articles covering desipramine 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

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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 7. 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 desipramine. 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 desipramine. 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 desipramine: Antidepressants, Tricyclic •

Systemic - U.S. Brands: Anafranil; Asendin; Aventyl; Elavil; Endep; Norfranil; Norpramin; Pamelor; Sinequan; Surmontil; Tipramine; Tofranil; Tofranil-PM; Vivactil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202055.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 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

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

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 “desipramine” (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 6822 26 999 6 30 7883

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 “desipramine” (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 desipramine 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 desipramine. 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 desipramine. 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 “desipramine”:

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Attention Deficit Disorder with Hyperactivity http://www.nlm.nih.gov/medlineplus/attentiondeficitdisorderwithhyperactivity.t ml Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on desipramine. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Antidepressants for Cyclic Vomiting Syndrome Source: Canal Winchester, OH: Cyclic Vomiting Syndrome Association, USA/Canada. 2002. [3 p]. Contact: Available from Cyclic Vomiting Syndrome Association, USA/Canada. 3585 Cedar Hill Road, NW, Canal Winchester, OH 43110. (614) 837-2586. Fax (614) 837-2586. E-mail: [email protected]. Website: www.cvsaonline.org. PRICE: Single copy free. Summary: This newsletter article discusses the use of antidepressants in the treatment of cyclic vomiting in mitochondrial disease. Cyclic vomiting refers to discrete and severe episodes of vomiting, nausea, and lethargy (severe tiredness). Episodes are discrete in that the sufferer is free of nausea and vomiting between episodes. Episodes can occur on a routine schedule, be triggered by physical or psychological stress, or appear to come at random. Cyclic vomiting has many known causes, including intestinal blockage, brain disorders, kidney disease, and several different metabolic disorders. Many of these causes are treatable, so a careful diagnostic work up is important. However, in the vast majority of cases, none of the above causes can be found, and these individuals are given the diagnosis of cyclic vomiting syndrome (CVS). Antidepressants are particularly useful in controlling functional symptoms in conditions including irritable bowel syndrome, functional dyspepsia, and fibromyalgia. Benefits on the physical symptoms can be independent of the drugs' psychiatric effects. The tricyclic antidepressants (TCAs), such as amitriptyline, nortriptyline, or desipramine, appear particularly useful, even in low daily dosages that would be considered subtherapeutic from the psychiatric standpoint. No single TCA has surfaced as superior to the other for CVS, although

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amitriptyline is most often utilized. The author offers guidelines for administration and dosage, patient selection, and coping with side effects of these drugs. 1 figure. 9 references. 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 desipramine. 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/

•

WebMDHealth: 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 desipramine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with desipramine. 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 desipramine. 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.

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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 “desipramine” (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 “desipramine”. 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 “desipramine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “desipramine” (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

•

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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on desipramine: •

Basic Guidelines for Desipramine Desipramine hydrochloride overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002626.htm Norpramin overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002512.htm

•

Signs & Symptoms for Desipramine Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Blurred vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Breathing slowed and labored Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm

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Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Comatose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Incoordination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Irregular heartbeat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Muscle rigidity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Restlessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Stupor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Urinary hesitancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003143.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Desipramine Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm

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Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm •

Background Topics for Desipramine Low body temperature Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000038.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Shock Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000039.htm Vital signs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002341.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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DESIPRAMINE 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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [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] 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] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [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] 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] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenosinetriphosphatase: A group of enzymes which catalyze the hydrolysis of ATP coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA. EC 3.6.1.3. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of

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each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]

Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] 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] 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] Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [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]

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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] 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] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-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] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It

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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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amodiaquine: A 4-aminoquinoquinoline compound with anti-inflammatory properties. [NIH]

Amoxapine: The N-demethylated derivative of the antipsychotic agent loxapine that works by blocking the reuptake of norepinephrine, serotonin, or both. It also blocks dopamine receptors. [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] 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]

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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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]

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Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [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] 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiarrheals: Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the

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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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodics: Medicines that help reduce or stop muscle spasms in the intestines. Examples are dicyclomine (dy-SY-klo-meen) (Bentyl) and atropine (AH-tro-peen) (Donnatal). [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [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] Asymptomatic: Having no signs or symptoms of disease. [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

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entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron 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] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [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] 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] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of

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fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [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] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] 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] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [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]

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Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It 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] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] 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 Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]

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Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [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 for the respiration cycle of plants and animals. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] 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] 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] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [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,

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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] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] 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] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] 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] 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] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing

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acetylcholine or a related compound. [EU] 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] 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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [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] 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]

Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clenbuterol: A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. [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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU]

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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] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement

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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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished.

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[NIH]

Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] 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] 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]

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] 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] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Crack Cocaine: The purified, alkaloidal, extra-potent form of cocaine. It is smoked (freebased), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term "crack" was derived from the crackling sound made upon igniting of this form of cocaine for smoking. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH]

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Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclic Vomiting Syndrome: Sudden, repeated attacks of severe vomiting (especially in children), nausea, and physical exhaustion with no apparent cause. Can last from a few hours to 10 days. The episodes begin and end suddenly. Loss of fluids in the body and changes in chemicals in the body can require immediate medical attention. Also called abdominal migraine. [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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Debrisoquin: An adrenergic neuron-blocking drug similar in effects to guanethidine. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4hydroxylase polymorphism. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU]

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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] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] 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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating

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release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diosmin: A bioflavonoid that strengthens vascular walls. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [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 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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy;

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superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [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] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug 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] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [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] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] 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

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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] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] 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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] 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] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [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] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health.

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[NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [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] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] 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] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]

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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 Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] 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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH]

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Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescence Polarization Immunoassay: Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluphenazine: A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and

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diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] 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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] 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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [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] 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]

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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] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Guanethidine: An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g.,

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vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoperfusion: Removal of toxins or metabolites from the circulation by the passing of blood, within a suitable extracorporeal circuit, over semipermeable microcapsules containing adsorbents (e.g., activated charcoal) or enzymes, other enzyme preparations (e.g., gel-entrapped microsomes, membrane-free enzymes bound to artificial carriers), or other adsorbents (e.g., various resins, albumin-conjugated agarose). [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] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU]

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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]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] 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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [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] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH]

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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] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Idiopathic: Describes a disease of unknown cause. [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 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] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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] Immunogenic: Producing immunity; evoking an immune response. [EU] 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] 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] Incubation: The development of an infectious disease from the entrance of the pathogen to

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the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [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] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] 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] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune,

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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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [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] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] 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

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action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] 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] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] 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] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [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] Lipid: Fat. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH]

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Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [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] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Lofepramine: A psychotropic imipramine derivative that acts as a tricyclic antidepressant and possesses few anticholinergic properties. It is metabolized to desipramine. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] 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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] 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

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radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [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] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Mefloquine: A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against Plasmodium falciparum with very few side effects. [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]

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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] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental 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 Health Services: Organized services to provide mental health care. [NIH] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methoxamine: An alpha-adrenergic agonist that causes prolonged peripheral vasoconstriction. It has little if any direct effect on the central nervous system. [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] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some

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anticonvulsant properties. [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] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible. [NIH] Micturition: The passage of urine; urination. [EU] 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] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Moclobemide: A reversible inhibitor of monoamine oxidase type A (RIMA) that has antidepressive properties. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration,

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pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] 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] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Neurons: Neurons which activate muscle cells. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] 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]

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Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] 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] Nail Biting: Common form of habitual body manipulation which is an expression of tension. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] 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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to

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stimulation of the nervous system. [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] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

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] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a

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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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [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] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Orthostatic: Pertaining to or caused by standing erect. [EU] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] 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] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH]

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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]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]

Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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 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] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU]

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Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [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] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] 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] Perphenazine: An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [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] 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] 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,

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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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] 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] 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] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH]

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Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [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] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU]

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Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]

Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [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]

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Prone: Having the front portion of the body downwards. [NIH] Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH]

Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] 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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Protriptyline: Tricyclic antidepressant similar in action and side effects to imipramine. It may produce excitation. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as

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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] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

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] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] 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]

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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] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and 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] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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]

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Rectum: The last 8 to 10 inches of the large intestine. [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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [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] 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] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Rheumatoid: Resembling rheumatism. [EU] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] 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] Rod: A reception for vision, located in the retina. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed

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pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [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] 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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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] 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.

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[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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] Sodium Lactate: The sodium salt of racemic or inactive lactic acid. It is a hygroscopic agent used intravenously as a systemic and urinary alkalizer. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] 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]

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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] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Sparteine: An alkaloid isolated from lupin beans, Lupinus luteus and Lupinus niger. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest because of genetic variation in its metabolism. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] 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] 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] 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] Splenomegaly: Enlargement of the spleen. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this

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group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH]

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Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] 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] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH]

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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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] 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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU]

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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] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transcutaneous: Transdermal. [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] 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] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [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

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or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trimipramine: Tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties. [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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] 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

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channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] 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] 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] 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 Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [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] Viloxazine: A morpholine derivative used as an antidepressant. It is similar in action to imipramine. [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] 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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH]

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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]

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] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]

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INDEX A Abdominal, 90, 119, 134, 148, 152, 158, 162, 166 Abdominal Pain, 90, 119, 148 Ablation, 6, 119 Acceptor, 119, 158 Acetylcholine, 20, 49, 119, 129, 156 Acoustic, 76, 77, 79, 81, 119 Actin, 119, 154, 155 Adaptation, 119, 129, 154, 160 Adenine, 119 Adenosine, 10, 119, 160 Adenosine Triphosphate, 10, 119, 160 Adenosinetriphosphatase, 62, 119 Adipocytes, 119, 149 Adjustment, 59, 119 Adrenal Cortex, 119, 133, 162 Adrenal Glands, 79, 119 Adrenal Medulla, 120, 128, 138, 139, 156 Adrenaline, 80, 120 Adrenergic, 4, 7, 12, 20, 31, 47, 57, 120, 122, 124, 134, 136, 137, 139, 143, 152, 153, 164, 171, 176 Adrenergic Agents, 4, 120 Adrenergic Agonists, 7, 120 Adrenergic Antagonists, 7, 120 Adverse Effect, 20, 57, 120, 160, 168 Aerobic, 120, 139 Afferent, 120, 149, 162 Affinity, 10, 18, 22, 76, 120, 168 Agarose, 120, 144 Agonist, 5, 11, 13, 47, 120, 125, 127, 136, 152, 155, 165 Agoraphobia, 120, 146, 158 Airway, 5, 120, 127 Airway Resistance, 5, 120 Akathisia, 120, 124 Albumin, 121, 144 Algorithms, 121, 126 Alkaline, 121, 122, 127 Alkaloid, 121, 125, 127, 128, 131, 154, 164, 169, 176 Allergen, 121, 167 Allylamine, 121 Alpha-1, 121, 122 Alternative medicine, 92, 121 Amantadine, 13, 34, 38, 67, 121 Amenorrhea, 121, 127

Amine, 14, 22, 76, 121, 145 Amino Acid Sequence, 121, 123 Amino Acids, 66, 121, 159, 161, 163 Amitriptyline, 3, 14, 25, 35, 42, 43, 44, 59, 68, 90, 106, 121 Ammonia, 121, 122 Amnestic, 122, 141 Amodiaquine, 86, 122 Amoxapine, 64, 122 Amphetamine, 22, 79, 122, 135, 151 Amygdala, 7, 122, 149 Anaesthesia, 122, 147 Anal, 14, 64, 122, 140, 150, 154 Analgesic, 31, 122, 127, 146, 149, 154, 157, 164, 170, 173 Analogous, 12, 21, 122, 173 Analytes, 14, 122 Anatomical, 122, 124, 129, 146 Anemia, 86, 122, 151 Anesthesia, 66, 120, 122, 148, 162 Anesthetics, 122, 125, 139 Animal model, 13, 14, 16, 122 Anions, 119, 121, 122, 148, 167 Anisotropy, 64, 123, 141 Antagonism, 20, 123, 137 Antiarrhythmic, 59, 123, 152 Antibacterial, 123, 169 Antibiotic, 123, 159, 169 Antibodies, 15, 21, 123, 143, 146, 160 Antibody, 21, 120, 123, 131, 141, 143, 145, 146, 147, 148, 151, 154, 165, 167, 169, 176 Anticholinergic, 16, 30, 57, 121, 123, 137, 150 Anticonvulsant, 76, 123, 128, 130, 152, 153, 159, 174 Antidiarrheals, 93, 123 Antiemetic, 123, 124, 129 Antifungal, 123, 149 Antigen, 120, 123, 131, 141, 145, 146, 147, 151, 165, 167 Anti-inflammatory, 3, 122, 123, 146, 170 Antipsychotic, 21, 52, 77, 122, 123, 129, 150, 156, 159, 166 Antipyretic, 124, 164 Antispasmodics, 93, 124 Antiviral, 121, 124 Anus, 122, 124, 127, 131

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Desipramine

Anxiety, 6, 11, 19, 29, 39, 67, 90, 120, 124, 141, 157, 158 Anxiety Disorders, 124, 158 Anxiolytic, 41, 76, 124 Aorta, 78, 124, 175 Aponeurosis, 124, 142 Apoptosis, 80, 124 Arginine, 11, 124, 156 Arterial, 121, 124, 133, 145, 163 Arteries, 73, 124, 126, 133, 154, 164 Arterioles, 124, 126, 127 Artery, 124, 133, 164 Aspartate, 76, 124, 149, 159 Assay, 14, 15, 16, 22, 24, 46, 124, 141, 146, 165 Asymptomatic, 24, 124 Atrial, 124, 133, 173 Atrioventricular, 124, 133 Atrium, 124, 133, 173, 175 Atropine, 124, 125 Attenuated, 79, 125, 136 Atypical, 29, 125, 156, 166 Auditory, 78, 125, 162, 174 Autonomic Nervous System, 16, 125, 133, 159, 168, 171 Autoradiography, 5, 8, 125 Axons, 125, 135, 162, 164 B Babesiosis, 125, 164 Baclofen, 13, 125 Bacteria, 123, 125, 135, 138, 140, 153, 163, 169, 173, 174 Bactericidal, 125, 139 Barbiturate, 81, 125 Basal Ganglia, 124, 125, 130, 142, 149, 157 Base, 119, 125, 134, 148, 164, 172 Behavior Therapy, 34, 125 Benign, 125, 142, 143, 155, 165 Bile, 125, 138, 142, 150, 170 Binding Sites, 32, 126 Biochemical, 21, 44, 64, 126, 139, 141, 159, 167 Biosynthesis, 126, 163 Biotechnology, 25, 92, 101, 126 Biotransformation, 126, 159 Bladder, 126, 174 Blastocyst, 126, 160 Bloating, 126, 148 Blood Coagulation, 126, 127 Blood Platelets, 76, 126, 167 Blood pressure, 47, 90, 116, 126, 129, 145, 154, 164, 168

Blood vessel, 126, 128, 129, 133, 138, 150, 152, 159, 168, 170, 172, 175 Body Composition, 11, 126 Body Fluids, 126, 168 Bolus, 12, 126 Bolus infusion, 126 Bone scan, 126, 166 Bowel, 33, 122, 126, 127, 148, 170 Bowel Movement, 127, 170 Brachytherapy, 127, 148, 165, 176 Bradykinin, 77, 127, 156 Brain Stem, 24, 127, 129 Bromocriptine, 13, 20, 30, 127 Bronchi, 127, 139, 173 Bronchial, 5, 127, 145 Bronchitis, 5, 127 Bronchodilator, 127, 130 Bulimia, 31, 34, 47, 65, 127 Bupivacaine, 127, 149 Buprenorphine, 8, 9, 33, 36, 37, 38, 42, 72, 127 Bupropion, 13, 27, 127 C Calcium, 11, 15, 127, 131, 168, 175 Calcium Channels, 15, 127 Capillary, 14, 63, 64, 127, 175 Capsaicin, 4, 66, 128 Carbamazepine, 3, 34, 47, 65, 128 Carbohydrate, 128, 143 Carbon Dioxide, 128, 135, 140, 160 Cardiac, 20, 31, 37, 54, 61, 77, 121, 123, 128, 130, 133, 139, 144, 149, 155, 164, 170 Cardiotoxicity, 44, 128 Cardiovascular, 20, 27, 31, 56, 77, 79, 122, 127, 128, 133, 136, 139, 167, 168 Cardiovascular System, 128, 133, 136 Carrier Proteins, 128, 165 Case report, 44, 51, 62, 128, 130 Case series, 128, 130 Catecholamine, 4, 72, 79, 80, 128, 136, 159 Caudal, 128, 146, 157, 161 Caudate Nucleus, 128, 157 Causal, 15, 128, 166 Cell Death, 124, 128, 155 Cell Differentiation, 128, 168 Cell Lineage, 15, 128 Cell membrane, 127, 128, 135, 142, 160, 168, 176 Cell proliferation, 129, 168 Cell Size, 129, 141 Central Nervous System Infections, 129, 143

179

Cerebellar, 75, 129 Cerebellum, 129, 141, 161 Cerebral, 9, 18, 32, 81, 125, 127, 129, 133, 134, 139, 140, 141, 151, 157, 164, 169, 171, 172 Cerebral Cortex, 81, 129, 140, 164 Cerebral hemispheres, 125, 127, 129, 172 Cerebrum, 129, 172 Chemoreceptor, 124, 129 Chest Pain, 88, 93, 129 Chin, 129, 152 Chloroquine, 50, 86, 129 Chlorpromazine, 73, 80, 129, 141, 159 Cholinergic, 5, 122, 124, 129 Chorea, 124, 130 Chromatin, 124, 130, 150 Chronic, 5, 6, 10, 12, 13, 20, 26, 30, 36, 52, 66, 70, 72, 79, 88, 90, 127, 130, 147, 149, 170, 171 Chronic Fatigue Syndrome, 90, 130 Cinchona, 130, 164 Citalopram, 25, 50, 72, 130 Clamp, 11, 130 Clenbuterol, 47, 130 Clinical study, 57, 58, 130, 133 Clinical trial, 4, 8, 9, 17, 20, 24, 69, 82, 101, 130, 133, 137, 159, 163, 165 Clomipramine, 26, 27, 33, 39, 43, 54, 56, 65, 68, 130 Clonazepam, 33, 36, 130 Clonic, 130, 152 Cloning, 126, 130 Coagulation, 126, 130, 144 Coca, 131 Coenzyme, 131, 141 Colitis, 131, 148 Collagen, 131, 140, 160 Colon, 131, 148 Combination Therapy, 36, 131 Comorbidity, 18, 27, 131 Complement, 131, 132, 167 Complementary and alternative medicine, 75, 83, 132 Complementary medicine, 75, 132 Complete remission, 132, 166 Compulsions, 132, 157 Computational Biology, 101, 132 Computed tomography, 132, 166 Computerized axial tomography, 132, 166 Concomitant, 52, 56, 132 Conduction, 19, 132 Confounding, 8, 132

Congenita, 132, 164 Congestion, 124, 132, 139 Conjugated, 132, 134, 144 Consciousness, 122, 132, 134, 135, 136, 163, 171 Constipation, 90, 124, 132, 141, 148 Constriction, 35, 132, 175 Consultation, 19, 132 Contamination, 132, 144 Continuum, 88, 132 Contractility, 133, 137 Contraindications, ii, 133 Controlled clinical trial, 52, 133 Controlled study, 27, 35, 45, 51, 64, 65, 67, 133 Convulsions, 116, 123, 125, 133, 137 Cor, 15, 133 Coronary, 10, 133, 154 Coronary Thrombosis, 133, 154 Cortex, 52, 133, 138, 162 Cortical, 20, 21, 72, 133, 139, 162, 164, 167 Cortisol, 11, 35, 47, 66, 121, 133 Crack Cocaine, 34, 78, 133 Cranial, 88, 129, 133, 143, 155, 159, 174 Craniocerebral Trauma, 133, 143 Cultured cells, 48, 64, 134 Curative, 134, 172 Cyclic, 5, 72, 106, 134, 143, 156 Cyclic Vomiting Syndrome, 106, 134 Cytochrome, 41, 48, 77, 134 Cytokine, 24, 134 Cytoplasm, 124, 128, 134, 143, 150, 154 Cytotoxic, 44, 128, 134, 165, 168 D Debrisoquin, 29, 134 Decidua, 134, 160 Degenerative, 134, 144, 154 Deletion, 6, 124, 134 Delirium, 123, 134 Dementia, 123, 135 Demethylation, 59, 135 Dendrites, 135, 156, 164 Dental Caries, 135, 141 Dentate Gyrus, 6, 7, 14, 135, 145 Deoxyribonucleic, 135, 166 Deoxyribonucleic acid, 135, 166 Depersonalization, 135, 158, 167 Depolarization, 135, 168 Depressive Disorder, 11, 17, 18, 21, 33, 39, 43, 53, 135, 150 Deprivation, 78, 135 Derealization, 135, 158

180

Desipramine

Dermatology, 82, 135 Deuterium, 63, 135, 145 Dextroamphetamine, 45, 122, 135, 152 Diabetes Mellitus, 11, 136, 142, 144 Diagnostic procedure, 85, 92, 136 Diarrhea, 90, 123, 136, 142, 148 Dicyclomine, 124, 136 Diffusion, 136, 174 Digestion, 125, 126, 136, 137, 148, 150, 170 Dilution, 14, 136 Diosmin, 76, 136 Direct, iii, 11, 58, 95, 136, 152, 164, 166, 171 Discrete, 14, 106, 136, 172 Disinfectant, 136, 139 Dissociation, 120, 136, 148 Dizziness, 136, 158 Dopa, 42, 136, 149 Dorsal, 24, 35, 136, 155, 161 Dorsum, 136, 137, 142 Dose-dependent, 18, 137 Double-blind, 8, 11, 20, 24, 26, 27, 28, 35, 39, 53, 56, 58, 64, 65, 66, 67, 68, 137 Double-blinded, 24, 66, 137 Doxepin, 34, 60, 137 Drive, ii, vi, 5, 7, 71, 137 Drug Interactions, 48, 90, 96, 137 Drug Monitoring, 35, 43, 47, 49, 53, 56, 63, 64, 68, 137 Dyskinesia, 124, 130, 137 Dyspepsia, 106, 137 Dysphoric, 135, 137 Dyspnea, 137, 158 Dystonia, 124, 137 E Echocardiography, 20, 137 Ectoderm, 137, 155 Effector, 119, 131, 137 Efficacy, 8, 9, 11, 13, 17, 18, 19, 20, 22, 24, 27, 33, 42, 67, 69, 80, 137, 173 Ejection fraction, 54, 137 Electric Conductivity, 123, 137 Electroconvulsive Therapy, 42, 137 Electrolyte, 134, 137, 144, 161, 168 Electrons, 125, 137, 148, 158, 165 Embryo, 16, 126, 128, 137, 138, 147 Empiric, 24, 138 Emulsion, 125, 138, 140 Endemic, 86, 138, 151 Endocrine System, 138, 155 Endogenous, 22, 31, 53, 62, 81, 120, 136, 138 Endorphins, 138, 156

Endothelium, 138, 156 Endothelium-derived, 138, 156 Endotoxin, 138, 174 Energy balance, 138, 149 Enkephalins, 138, 156 Enterohepatic, 138, 170 Enterohepatic Circulation, 138, 170 Entorhinal Cortex, 138, 145 Enuresis, 39, 54, 138 Environmental Health, 100, 102, 138 Enzymatic, 79, 127, 131, 135, 139, 145 Enzyme, 59, 131, 134, 137, 139, 143, 144, 152, 154, 163, 168, 170, 172, 176 Eosinophilic, 52, 139 Epinephrine, 11, 120, 136, 139, 156, 174 Ergot, 127, 139 Erythema, 139, 174 Erythrocytes, 122, 125, 139, 167 Estrogen, 72, 139, 162 Ethanol, 78, 130, 139 Ethnic Groups, 19, 139 Ethylmaleimide, 49, 139 Eukaryotic Cells, 139, 146 Evacuation, 132, 139, 158 Excitability, 139, 164 Excitation, 129, 139, 141, 156, 163 Excitatory, 5, 125, 139, 143 Exercise Test, 31, 139 Exhaustion, 123, 134, 139, 151 Exogenous, 126, 138, 139 External-beam radiation, 140, 148, 165, 176 Extracellular, 7, 15, 140, 153, 168 Extracellular Matrix, 140 Extracellular Space, 140, 153 Extracorporeal, 140, 144 Extraction, 40, 64, 140 Extrapyramidal, 120, 121, 124, 136, 140 F Family Planning, 101, 140 Fat, 119, 126, 133, 140, 149 Fatigue, 130, 140 Feces, 132, 140, 170 Fetus, 140, 160, 162 Fibrinogen, 10, 140, 172 Fibroblasts, 67, 140 Fissure, 135, 140, 162 Fixation, 140, 167 Flatus, 140, 142 Flow Cytometry, 11, 141 Fluorescence, 11, 47, 58, 141, 153 Fluorescence Polarization, 47, 141

181

Fluorescence Polarization Immunoassay, 47, 141 Fluorescent Dyes, 141 Fluorine, 36, 141 Fluphenazine, 56, 141 Fluvoxamine, 5, 26, 31, 35, 44, 48, 49, 52, 64, 141 Fold, 140, 141, 152 Forearm, 126, 141 Fourth Ventricle, 141, 150, 172 Friction, 120, 141 Frontal Lobe, 141, 162 Functional Disorders, 90, 141 G GABA, 13, 125, 130, 142, 168, 174 Gallbladder, 119, 142 Ganglia, 119, 142, 155, 159, 171 Ganglion, 79, 142, 155 Gap Junctions, 142, 171 Gas, 14, 44, 59, 63, 64, 122, 128, 136, 140, 141, 142, 145, 148, 156 Gastric, 14, 116, 142, 145 Gastrin, 142, 145 Gastrointestinal, 93, 127, 130, 133, 136, 139, 142, 151, 167, 168, 170 Gastrointestinal tract, 130, 139, 142, 167 Gene, 5, 6, 13, 16, 23, 29, 42, 126, 142, 154, 160 Gene Expression, 5, 13, 16, 42, 142 Genetics, 142, 159 Genotype, 53, 142, 159 Geriatric, 34, 44, 142 Gestation, 142, 160 Gestational, 7, 142 Gland, 119, 120, 142, 158, 167, 170, 172 Glucose, 11, 136, 142, 143, 144, 147 Glucose Intolerance, 136, 142 Glucose tolerance, 11, 142, 143 Glucose Tolerance Test, 11, 142, 143 Glutamate, 13, 87, 143 Glutamic Acid, 143, 156 Glycine, 143, 156 Glycoprotein, 140, 143, 174 Glycosidic, 143, 157 Governing Board, 143, 161 Granule, 75, 135, 143 Granulocytes, 143, 168, 176 Guanethidine, 134, 143 Guanylate Cyclase, 143, 156 H Habitual, 143, 155 Hallucinogen, 143, 159

Haloperidol, 45, 62, 77, 143 Haptens, 120, 143, 165 Headache, 86, 87, 88, 143, 162 Headache Disorders, 88, 143 Heart attack, 11, 144 Heartbeat, 116, 144, 170 Hemicrania, 144 Hemodiafiltration, 144, 174 Hemodialysis, 144, 174 Hemofiltration, 144, 174 Hemoglobin, 122, 139, 144 Hemoperfusion, 80, 144 Hemorrhage, 133, 143, 144, 170 Hemostasis, 10, 144, 167 Hepatic, 44, 50, 69, 77, 121, 134, 143, 144 Hepatitis, 46, 144 Hepatitis A, 46, 144 Hepatocytes, 144 Hepatovirus, 144 Heredity, 54, 142, 144 Heterogeneity, 120, 145 Heterogenic, 145 Heterogenous, 17, 145 Hippocampus, 6, 7, 14, 135, 145, 149, 164, 170 Histamine, 124, 137, 145, 153 Homogeneous, 59, 132, 145 Homologous, 145, 167, 171 Hormone, 15, 32, 45, 47, 62, 120, 133, 139, 142, 145, 147, 149, 158, 162, 168, 172 Hybrid, 145 Hybridization, 8, 145 Hydrogen, 119, 121, 125, 128, 135, 145, 153, 156, 157, 158 Hydrolysis, 119, 126, 145, 160, 161, 163 Hydroxylation, 29, 48, 53, 56, 57, 59, 65, 68, 72, 145 Hyperalgesia, 66, 145 Hypersensitivity, 46, 121, 145, 167 Hypersensitivity, Immediate, 145 Hypertension, 143, 145 Hypertrophy, 133, 145, 173 Hypnotic, 125, 145 Hypotension, 124, 133, 145 Hypothalamic, 15, 146 Hypothalamus, 8, 125, 146, 149, 162, 172 Hypothermia, 5, 146 I Ibuprofen, 3, 36, 146 Idiopathic, 88, 146 Immune response, 10, 123, 143, 146, 167, 170, 175

182

Desipramine

Immune system, 146, 150, 174, 176 Immunization, 146, 167 Immunoassay, 47, 52, 146 Immunogenic, 146, 165 Immunohistochemistry, 21, 146 Immunologic, 146, 165 Immunology, 46, 120, 141, 146 Impairment, 20, 134, 137, 146, 152, 163 Implant radiation, 146, 148, 165, 176 Impotence, 146, 176 In situ, 8, 15, 146 In Situ Hybridization, 8, 15, 146 In vitro, 11, 15, 23, 24, 48, 69, 73, 80, 146 In vivo, 7, 10, 23, 37, 48, 72, 81, 146, 153, 170 Incubation, 86, 146, 147 Incubation period, 86, 147 Induction, 6, 123, 147, 148, 162 Infarction, 147 Infection, 86, 134, 147, 150, 156, 159, 170, 174, 175, 176 Infertility, 127, 147 Inflammation, 5, 121, 123, 127, 131, 144, 147, 155, 160, 171 Infusion, 7, 10, 147 Ingestion, 25, 81, 143, 147, 161 Inhalation, 147, 161 Innervation, 137, 147 Inorganic, 147, 154 Inositol, 72, 147 Inotropic, 136, 147 Inpatients, 25, 60, 68, 147 Insight, 17, 22, 147 Insomnia, 147, 162, 173 Insulin, 11, 81, 143, 147 Insulin-dependent diabetes mellitus, 147 Interleukin-1, 72, 148 Interleukin-2, 148 Internal radiation, 148, 165, 176 Interstitial, 106, 127, 140, 148, 176 Intestinal, 106, 143, 148 Intestine, 126, 138, 148, 166, 168 Intoxication, 134, 148, 176 Intracellular, 13, 147, 148, 156, 161, 165, 168 Intravenous, 147, 148 Intrinsic, 120, 148 Involuntary, 130, 138, 148, 155, 166, 172 Ion Channels, 148, 160, 171 Ionization, 65, 148 Ions, 125, 127, 136, 137, 145, 148, 153, 168 Irradiation, 6, 148, 176

Irritable Bowel Syndrome, 90, 93, 106, 141, 148 K Kb, 100, 148 Ketamine, 148, 159 Ketoconazole, 40, 48, 149 Kidney Disease, 100, 106, 149 Kinetic, 149 L Lactation, 149, 158, 162 Larynx, 149, 173, 174 Leptin, 11, 149 Lesion, 77, 149, 150, 172, 174 Lethargy, 106, 149 Levo, 136, 149 Levodopa, 136, 149 Lidocaine, 24, 65, 149, 152 Life cycle, 120, 149 Ligaments, 133, 149 Ligands, 10, 16, 22, 149 Limbic, 72, 122, 149, 162 Limbic System, 122, 149, 162 Lipid, 49, 64, 147, 149, 150 Lipid Bilayers, 49, 149 Lipopolysaccharide, 72, 150 Lithium, 35, 39, 50, 51, 55, 60, 123, 150 Liver, 49, 51, 52, 119, 121, 125, 129, 130, 135, 138, 140, 142, 143, 144, 150, 166 Liver scan, 150, 166 Localization, 146, 150 Localized, 135, 140, 147, 150, 160, 174 Locomotion, 150, 160 Locomotor, 18, 72, 150 Locus Coeruleus, 12, 150 Lofepramine, 51, 63, 150 Longitudinal study, 11, 19, 150 Loxapine, 122, 150 Lutein Cells, 150, 162 Lymphatic, 138, 147, 150, 169 Lymphocytes, 123, 146, 148, 150, 169, 176 Lymphoid, 123, 150 M Macrophage, 148, 150 Magnetic Resonance Imaging, 150, 166 Malaria, 50, 86, 130, 151 Malaria, Falciparum, 151 Malaria, Vivax, 151 Malignant, 151, 155, 157, 165 Manic, 123, 150, 151, 164 Manifest, 17, 151 Mazindol, 13, 151 Medial, 8, 77, 151, 157

183

Mediate, 7, 13, 15, 136, 151 Mediator, 136, 148, 151, 167 Medical Records, 151, 166 Medical Staff, 137, 151 MEDLINE, 101, 151 Medulloblastoma, 49, 151 Mefloquine, 86, 151 Meiosis, 151, 171 Melanin, 150, 151, 159, 174 Memory, 22, 67, 134, 135, 152 Meninges, 129, 133, 152 Menstrual Cycle, 152, 162 Mental Disorders, 21, 152, 163, 164 Mental Health, iv, 4, 9, 16, 100, 102, 152, 164 Mental Health Services, iv, 4, 9, 102, 152 Mephenytoin, 43, 65, 152 Mercury, 141, 152 Mesencephalic, 150, 152 Mesenteric, 73, 152 Mesentery, 152 Mesolimbic, 30, 82, 124, 152 Meta-Analysis, 61, 152 Metabolic disorder, 106, 152 Metabolite, 13, 36, 46, 63, 67, 126, 130, 152, 156 Methamphetamine, 79, 152 Methoxamine, 35, 152 Methylphenidate, 17, 20, 42, 45, 53, 63, 152 Mexiletine, 4, 152 Mianserin, 12, 44, 57, 153 Microbe, 153, 173 Microbiology, 80, 119, 125, 153 Microdialysis, 7, 153 Microorganism, 153, 158, 176 Microscopy, 5, 15, 153 Microscopy, Confocal, 5, 153 Micturition, 77, 153 Mitochondrial Swelling, 153, 155 Mitosis, 124, 153 Mitotic, 153, 175 Mobilization, 11, 153 Moclobemide, 31, 53, 153 Modification, 93, 153, 164 Molecular Structure, 153, 174 Molecule, 123, 125, 126, 131, 136, 137, 138, 139, 143, 145, 153, 157, 158, 165, 168 Monitor, 153, 157 Monoamine, 122, 136, 153, 154 Monoclonal, 148, 154, 165, 176 Monocytes, 148, 154 Monogenic, 55, 154

Mononuclear, 154, 174 Mood Disorders, 9, 23, 154 Morphine, 65, 127, 154, 155, 157 Morphological, 5, 138, 154 Motility, 142, 154, 167 Motion Sickness, 154, 155 Motor Neurons, 5, 154 Movement Disorders, 121, 124, 154 Mucinous, 142, 154 Mucosa, 154, 162 Mucus, 90, 154 Multidrug resistance, 80, 154 Multivariate Analysis, 21, 154 Muscle Contraction, 88, 154 Muscle relaxant, 154, 159 Muscle Spindles, 154, 160 Mydriatic, 154, 176 Myocardial infarction, 10, 63, 133, 154 Myocarditis, 46, 155 Myocardium, 154, 155 Myosin, 154, 155 Myotonia, 155, 164 N Nail Biting, 26, 155 Naloxone, 66, 155 Naltrexone, 72, 155 Narcolepsy, 135, 152, 155 Narcotic, 154, 155, 173 Nausea, 106, 123, 124, 134, 155, 158, 162 Necrosis, 50, 72, 124, 147, 154, 155 Neonatal, 17, 155 Neoplasm, 155, 174 Nephropathy, 149, 155 Nerve Growth Factor, 15, 155 Nervous System, 5, 16, 22, 65, 119, 120, 122, 125, 127, 129, 131, 133, 135, 142, 143, 149, 151, 152, 154, 155, 156, 159, 161, 167, 171 Neural, 5, 15, 120, 155, 168 Neural Crest, 15, 155 Neuroendocrine, 42, 53, 54, 76, 155 Neuroleptic, 54, 120, 123, 156 Neuromuscular, 119, 156 Neuromuscular Junction, 119, 156 Neuronal, 6, 13, 21, 49, 73, 76, 87, 127, 130, 156 Neurons, 5, 7, 12, 15, 21, 22, 37, 75, 77, 87, 131, 135, 139, 142, 149, 154, 155, 156, 164, 171 Neuropathy, 3, 42, 77, 156 Neuropharmacology, 9, 13, 72, 79, 156

184

Desipramine

Neurotransmitter, 4, 15, 20, 22, 60, 119, 127, 136, 142, 143, 145, 148, 156, 168, 170, 171 Neutrons, 148, 156, 165 Nitric Oxide, 87, 156 Nitrogen, 64, 120, 121, 140, 156, 174 Nonverbal Communication, 156, 164 Nortriptyline, 3, 14, 35, 59, 106, 156 Nuclear, 15, 125, 138, 139, 142, 149, 155, 156, 172 Nuclei, 122, 137, 149, 150, 153, 156, 157, 160 Nucleic acid, 145, 146, 156, 157, 166 Nucleic Acid Hybridization, 145, 157 Nucleus, 5, 8, 23, 124, 130, 134, 135, 139, 150, 151, 154, 156, 157, 162, 163, 168 Nucleus Accumbens, 23, 157 O Obsessive-Compulsive Disorder, 27, 29, 64, 68, 141, 157 Occipital Lobe, 157, 175 Oligosaccharides, 80, 157 Opiate, 8, 13, 36, 154, 155, 157 Opium, 154, 157 Optic Chiasm, 146, 157, 162 Orthostatic, 124, 157 Osteogenic sarcoma, 157 Osteosarcoma, 41, 157 Outpatient, 19, 47, 157 Overdosage, 53, 55, 157 Overdose, 115, 157 Ovum, 134, 142, 149, 158, 162 Oxidation, 43, 64, 77, 119, 126, 134, 158 Oxygen Consumption, 139, 158 Oxytocic, 158, 169 Oxytocin, 7, 158 P Palliative, 158, 172 Pancreas, 119, 147, 158 Panic, 27, 30, 38, 58, 81, 141, 146, 158 Panic Disorder, 27, 38, 58, 141, 146, 158 Parasite, 86, 158 Paresthesias, 158 Parkinsonism, 124, 149, 158 Paroxetine, 3, 11, 15, 35, 37, 48, 59, 158 Paroxysmal, 144, 158 Partial remission, 158, 166 Parturition, 158, 162 Pathogen, 146, 158 Pathologic, 124, 133, 145, 158, 159, 175 Pathologic Processes, 124, 159 Pathophysiology, 7, 18, 159

Patient Education, 93, 106, 110, 112, 117, 159 Patient Selection, 107, 159 Penicillin, 123, 159 Peptide, 149, 159, 161, 163 Perfusion, 9, 159 Peripheral Nervous System, 138, 156, 159, 162, 170 Perphenazine, 14, 159 Pharmacodynamics, 41, 159 Pharmacogenetics, 56, 64, 159 Pharmacokinetic, 159 Pharmacologic, 80, 122, 159, 173 Pharmacotherapy, 7, 9, 13, 16, 18, 28, 90, 159 Phencyclidine, 70, 159 Phenotype, 43, 60, 159 Phenylalanine, 159, 174 Phenytoin, 44, 128, 159 Phospholipases, 160, 168 Phospholipids, 140, 147, 160 Phosphorus, 64, 127, 160 Physiologic, 120, 126, 136, 152, 160, 165 Physiology, 5, 40, 41, 81, 119, 160 Pilot study, 30, 39, 67, 160 Placenta, 16, 160, 162 Plants, 121, 125, 128, 131, 142, 156, 160, 173 Plasma, 11, 14, 20, 22, 34, 35, 40, 41, 44, 45, 48, 52, 54, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 68, 69, 76, 121, 123, 128, 140, 142, 143, 144, 160, 167 Plasma cells, 123, 160 Plasticity, 78, 160 Platelet Activation, 160, 168 Platelet Aggregation, 10, 156, 160 Platelets, 10, 37, 39, 46, 49, 76, 156, 160, 172 Pleomorphic, 157, 160 Pneumonia, 52, 133, 160 Poisoning, 80, 134, 139, 148, 152, 155, 161 Polymorphic, 57, 134, 135, 161 Polymorphism, 134, 161 Polypeptide, 121, 131, 140, 145, 161, 162 Pons, 127, 141, 161 Posterior, 122, 129, 136, 137, 157, 158, 161 Postherpetic Neuralgia, 121, 161 Postnatal, 78, 161, 169 Postsynaptic, 30, 161, 168, 171 Post-traumatic, 144, 154, 161 Potassium, 161, 164 Potentiates, 72, 148, 161

185

Potentiating, 122, 161 Potentiation, 77, 161, 168 Practicability, 161, 173 Practice Guidelines, 102, 161 Precipitating Factors, 144, 161 Preclinical, 12, 72, 161 Precursor, 136, 137, 138, 139, 149, 156, 159, 161, 174 Predictive factor, 8, 162 Prefrontal Cortex, 77, 162 Premenstrual Syndrome, 62, 90, 162 Prenatal, 8, 78, 138, 162 Preoptic Area, 8, 162 Presynaptic, 137, 156, 162, 171 Presynaptic Terminals, 137, 162 Prevalence, 54, 162 Primitive neuroectodermal tumors, 151, 162 Probe, 153, 162 Procaine, 149, 162 Progesterone, 162, 170 Prognostic factor, 33, 162 Progression, 122, 162 Progressive, 128, 135, 155, 160, 162, 174 Projection, 156, 162, 164 Prolactin, 47, 127, 162 Prone, 76, 86, 163 Propafenone, 59, 163 Prophase, 163, 171 Prospective study, 11, 60, 150, 163 Protease, 48, 131, 163 Protease Inhibitors, 48, 163 Protein Kinases, 23, 163 Protein S, 126, 163 Proteolytic, 67, 121, 131, 140, 163 Protocol, 6, 11, 19, 30, 163 Protozoa, 153, 163 Protozoal, 86, 163 Protozoan, 129, 151, 163 Protriptyline, 54, 163 Psychiatric, 6, 16, 17, 18, 23, 25, 53, 106, 152, 163 Psychic, 152, 163, 167 Psychoactive, 22, 47, 163, 176 Psychosis, 123, 142, 163, 164 Psychotherapy, 17, 34, 93, 164 Psychotomimetic, 122, 136, 164 Psychotropic, 150, 164 Public Health, 9, 16, 102, 164 Public Policy, 101, 164 Publishing, 19, 25, 164

Pulmonary, 120, 126, 133, 139, 144, 164, 175 Pulmonary Artery, 126, 164, 175 Pulmonary hypertension, 133, 164 Pulse, 47, 117, 154, 164 Pyramidal Cells, 72, 135, 164 Q Quality of Life, 13, 93, 164 Quinidine, 48, 59, 72, 130, 164 Quinine, 72, 86, 130, 164 Quinpirole, 72, 165 R Race, 136, 165, 168 Racemic, 136, 165, 168 Radiation, 125, 140, 141, 148, 165, 166, 176 Radiation therapy, 140, 148, 165, 176 Radioactive, 125, 126, 145, 146, 148, 150, 157, 165, 166, 176 Radioimmunoassay, 8, 165 Radiolabeled, 148, 165, 176 Radiological, 6, 165 Radiology, 165 Radiotherapy, 127, 148, 165, 176 Randomized, 8, 9, 11, 13, 17, 19, 20, 24, 137, 165 Randomized clinical trial, 8, 20, 165 Reagent, 139, 165 Receptors, Serotonin, 165, 167 Rectum, 124, 127, 131, 140, 142, 166 Refer, 1, 131, 136, 138, 140, 150, 156, 164, 166 Reflex, 5, 20, 35, 77, 154, 166 Refraction, 123, 166, 169 Refractory, 17, 32, 50, 51, 60, 61, 166 Regeneration, 16, 166 Regimen, 87, 137, 159, 166 Relapse, 60, 62, 166 Remission, 54, 166 Retrograde, 5, 166 Retroperitoneal, 119, 166 Retrospective, 24, 25, 166 Retrospective Studies, 24, 166 Retrospective study, 25, 166 Rheumatoid, 129, 166 Ribonucleic acid, 8, 166 Ribose, 119, 166 Rigidity, 116, 158, 160, 166 Risk factor, 10, 163, 166 Risperidone, 17, 166 Rod, 130, 166 S Scans, 18, 166

186

Desipramine

Schizoid, 167, 176 Schizophrenia, 21, 137, 150, 166, 167, 176 Schizotypal Personality Disorder, 135, 167, 176 Screening, 13, 22, 130, 167 Secretion, 66, 127, 136, 145, 147, 149, 154, 167 Secretory, 167, 171 Sedative, 76, 121, 125, 146, 167, 174 Sedentary, 87, 167 Seizures, 128, 130, 134, 158, 159, 167 Semisynthetic, 127, 167 Sensibility, 122, 145, 167 Sensitization, 87, 167 Serologic, 146, 167 Sertraline, 8, 10, 12, 29, 32, 37, 53, 56, 62, 64, 66, 91, 167 Serum, 27, 33, 39, 46, 47, 51, 52, 53, 57, 59, 62, 121, 131, 165, 167, 174 Serum Albumin, 165, 167 Shock, 12, 117, 167, 173 Side effect, 16, 17, 20, 62, 63, 90, 95, 107, 120, 124, 130, 151, 163, 168, 170, 173 Signal Transduction, 13, 147, 168 Signs and Symptoms, 166, 168 Skeletal, 130, 154, 164, 168 Skull, 133, 168, 172 Small intestine, 145, 148, 168 Smoking Cessation, 127, 168 Smooth muscle, 121, 127, 145, 154, 168, 170 Social Environment, 164, 168 Sodium, 30, 164, 168, 174 Sodium Channels, 164, 168, 175 Sodium Lactate, 30, 168 Solitary Nucleus, 125, 168 Solvent, 139, 168 Soma, 164, 169 Somatic, 149, 151, 153, 159, 162, 169, 174 Sound wave, 132, 169 Sparteine, 43, 48, 169 Spastic, 148, 169 Spasticity, 125, 169 Specialist, 107, 169 Species, 86, 128, 139, 145, 151, 153, 154, 158, 164, 165, 169, 170, 175, 176 Specificity, 64, 76, 120, 127, 169 Spectrum, 17, 149, 169 Spinal cord, 125, 127, 129, 142, 152, 155, 156, 159, 166, 169, 171 Spleen, 150, 169 Splenomegaly, 86, 169

Stabilization, 160, 169 Staging, 166, 169 Steel, 130, 169 Stem Cells, 15, 169 Steroid, 133, 169 Stimulant, 18, 122, 135, 145, 152, 170 Stimulus, 133, 137, 139, 147, 148, 158, 166, 170 Stomach, 119, 142, 143, 145, 155, 168, 169, 170 Stool, 90, 131, 148, 170 Stress, 11, 13, 14, 22, 30, 72, 106, 125, 128, 133, 142, 148, 155, 170, 174 Striatum, 52, 157, 170 Stroke, 57, 100, 170 Structure-Activity Relationship, 18, 170 Stupor, 116, 149, 155, 170 Subacute, 20, 147, 170 Subarachnoid, 141, 143, 170 Subclinical, 147, 167, 170 Subcutaneous, 12, 119, 170 Subiculum, 145, 170 Subspecies, 169, 170 Substance P, 152, 167, 170 Substrate, 22, 49, 134, 137, 170 Sudden death, 11, 30, 43, 57, 170 Sulindac, 3, 170 Suppression, 72, 171 Supraspinal, 125, 171 Sympathetic Nervous System, 125, 171 Sympathomimetic, 122, 135, 136, 139, 152, 156, 171 Symptomatic, 121, 123, 171 Symptomatic treatment, 121, 123, 171 Symptomatology, 22, 171 Synapse, 22, 120, 156, 162, 171, 173 Synapsis, 171 Synaptic, 13, 22, 156, 168, 171 Synaptic Transmission, 22, 171 Syncope, 20, 171 Synergistic, 93, 162, 171, 172 Systemic, 24, 96, 124, 126, 129, 134, 139, 147, 148, 165, 168, 171, 173, 176 Systemic lupus erythematosus, 129, 171 Systemic therapy, 129, 171 T Tachycardia, 69, 171 Tardive, 124, 130, 172 Telencephalon, 125, 129, 172 Temporal, 23, 65, 122, 144, 145, 172 Temporal Lobe, 122, 172 Tendon, 142, 169, 172

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Thalamus, 149, 162, 172 Therapeutics, 29, 31, 32, 39, 43, 44, 48, 54, 66, 81, 96, 172 Thermal, 123, 136, 156, 172 Third Ventricle, 146, 172 Thrombin, 140, 160, 172 Thrombocytes, 160, 172 Thrombosis, 163, 170, 172 Thyroid, 32, 55, 67, 81, 172, 174 Tic, 26, 172 Tissue, 21, 24, 42, 119, 123, 125, 127, 130, 131, 139, 140, 142, 146, 148, 149, 150, 151, 152, 154, 155, 156, 159, 160, 166, 168, 169, 170, 171, 172, 174 Tolerance, 127, 130, 143, 172 Tomography, 16, 18, 36, 132, 172 Tone, 5, 20, 169, 172 Tonic, 130, 152, 172 Tonus, 172, 173 Topical, 4, 24, 139, 173 Toxic, iv, 30, 57, 125, 130, 151, 156, 173 Toxicity, 38, 50, 53, 67, 69, 128, 137, 152, 173 Toxicokinetics, 173 Toxicology, 13, 53, 64, 79, 102, 173 Toxins, 123, 127, 144, 147, 173 Trace element, 141, 173 Trachea, 5, 127, 149, 172, 173 Traction, 130, 173 Tractus, 5, 173 Tramadol, 4, 173 Transcutaneous, 4, 173 Transduction, 168, 173 Transfection, 126, 173 Translocation, 22, 173 Transmitter, 119, 136, 148, 151, 156, 173 Trauma, 134, 155, 173 Treatment Outcome, 18, 173 Triazolam, 80, 173 Tricuspid Atresia, 133, 173 Trigger zone, 124, 174 Trimipramine, 90, 174 Trophic, 21, 174 Tryptophan, 68, 131, 167, 174 Tubercle, 157, 174 Tumor Necrosis Factor, 24, 174 Tumour, 72, 142, 174 Tyrosine, 15, 136, 174 U Ulcer, 15, 174 Ultrafiltration, 52, 144, 174 Ureters, 174, 175

Urethra, 174 Urinary, 10, 68, 116, 136, 138, 168, 174 Urine, 13, 47, 63, 64, 126, 138, 153, 174, 175 Urticaria, 38, 174 Uterine Contraction, 158, 174 V Vaccine, 163, 174 Vagal, 5, 174 Vagus Nerve, 168, 174 Valproic Acid, 57, 174 Vascular, 20, 121, 136, 138, 144, 145, 147, 156, 160, 174, 175 Vasoconstriction, 139, 152, 175 Vasodilator, 127, 136, 145, 175 Vein, 35, 148, 157, 175 Venlafaxine, 17, 18, 30, 35, 36, 64, 69, 87, 175 Ventral, 146, 157, 161, 175 Ventricle, 122, 124, 128, 133, 145, 157, 164, 173, 175 Ventricular, 69, 133, 137, 163, 173, 175 Ventricular Dysfunction, 137, 175 Venules, 126, 127, 175 Verapamil, 73, 175 Vesicoureteral, 77, 175 Vesicular, 80, 175 Veterinary Medicine, 73, 101, 175 Viloxazine, 64, 175 Vinblastine, 79, 175 Vinca Alkaloids, 175 Viral, 14, 23, 48, 173, 175 Virulence, 125, 173, 175 Virus, 129, 173, 175 Visceral, 125, 149, 174, 175 Visceral Afferents, 125, 174, 175 Visual Cortex, 78, 175 Vitamin A, 147, 175 Vitro, 16, 23, 24, 176 Vivo, 23, 176 Voltage-gated, 15, 176 W White blood cell, 123, 150, 154, 160, 176 Windpipe, 172, 176 Withdrawal, 13, 20, 47, 70, 134, 176 X Xenograft, 122, 176 X-ray, 132, 141, 148, 157, 165, 166, 176 X-ray therapy, 148, 176 Y Yeasts, 159, 176 Yohimbine, 20, 72, 176

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