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

LAMOTRIGINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

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LAMOTRIGINE 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., 1960Lamotrigine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84477-1 1. Lamotrigine-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 lamotrigine. 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 LAMOTRIGINE ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lamotrigine................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 14 The National Library of Medicine: PubMed ................................................................................ 14 CHAPTER 2. NUTRITION AND LAMOTRIGINE ................................................................................. 59 Overview...................................................................................................................................... 59 Finding Nutrition Studies on Lamotrigine.................................................................................. 59 Federal Resources on Nutrition ................................................................................................... 63 Additional Web Resources ........................................................................................................... 64 CHAPTER 3. CLINICAL TRIALS AND LAMOTRIGINE ....................................................................... 65 Overview...................................................................................................................................... 65 Recent Trials on Lamotrigine....................................................................................................... 65 Keeping Current on Clinical Trials ............................................................................................. 66 CHAPTER 4. PATENTS ON LAMOTRIGINE........................................................................................ 69 Overview...................................................................................................................................... 69 Patents on Lamotrigine................................................................................................................ 69 Patent Applications on Lamotrigine ............................................................................................ 72 Keeping Current .......................................................................................................................... 76 CHAPTER 5. BOOKS ON LAMOTRIGINE ........................................................................................... 77 Overview...................................................................................................................................... 77 Book Summaries: Federal Agencies.............................................................................................. 77 Book Summaries: Online Booksellers........................................................................................... 78 Chapters on Lamotrigine.............................................................................................................. 78 CHAPTER 6. PERIODICALS AND NEWS ON LAMOTRIGINE ............................................................. 81 Overview...................................................................................................................................... 81 News Services and Press Releases................................................................................................ 81 Academic Periodicals covering Lamotrigine ................................................................................ 84 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 87 Overview...................................................................................................................................... 87 U.S. Pharmacopeia....................................................................................................................... 87 Commercial Databases ................................................................................................................. 88 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 91 Overview...................................................................................................................................... 91 NIH Guidelines............................................................................................................................ 91 NIH Databases............................................................................................................................. 93 Other Commercial Databases....................................................................................................... 95 APPENDIX B. PATIENT RESOURCES ................................................................................................. 97 Overview...................................................................................................................................... 97 Patient Guideline Sources............................................................................................................ 97 Finding Associations.................................................................................................................... 99 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 101 Overview.................................................................................................................................... 101 Preparation................................................................................................................................. 101 Finding a Local Medical Library................................................................................................ 101 Medical Libraries in the U.S. and Canada ................................................................................. 101 ONLINE GLOSSARIES................................................................................................................ 107 Online Dictionary Directories ................................................................................................... 107

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LAMOTRIGINE DICTIONARY................................................................................................. 109 INDEX .............................................................................................................................................. 153

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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 lamotrigine 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 lamotrigine, 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 lamotrigine, 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 lamotrigine. 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 lamotrigine, 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 lamotrigine. 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 LAMOTRIGINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lamotrigine.

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

Treatment of the Epileptic Patient in the Dental Office Source: New York State Dental Journal. 64(2): 26-31. February 1998. Contact: Available from Dental Society of the State of New York. 7 Elk Street, Albany, NY 12207. (518) 465-0044; Fax (518) 427-0461. Summary: Epilepsy is a relatively common problem in children, adults, and older adults. Dentists need to be familiar with the various manifestations of the disease, the anticonvulsant medications (AEDs) that patients are taking, and the complications and side effects of these drugs. In this article, the types of seizures and AEDs in common use are described, and the authors offer guidelines for treatment planning. Drugs covered include phenobarbital, Dilantin (phenytoin), Tegretol (carbamazepine), Depakene and Depakote (volproic acid and divalproex), Mysoline (primidone), Zarontine

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(ethosuximide), Lamictal (lamotrigine), Neurontin (gabapentin), Tranxene (clorazepate dipotassium), and Topamax (topiramate); the use of a ketosis diet to control seizures is also discussed. Recommendations are also provided for managing the patient who has a seizure in the dental office, with emergency protocols and referral guidelines noted. The authors emphasize that the well-controlled patient with epilepsy can be treated safely and comfortably in the average dental office. 1 table. 12 references.

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

Project Title: ACUTE TREATMENT OF BIPOLAR II DEPRESSION Principal Investigator & Institution: Suppes, Patricia; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This exploratory, stage 3 R21 proposal is designed to provide data on the acute treatment response of an understudied mental health population --bipolar II disorder (BDII). This disorder is characterized by major depression and periods of hypomania observable by others. There is now clear recognition of the stability of this diagnosis, and increased recognition of the severity and frequency of depressive symptoms. The overall severity, disability, and suicide risk is considered equal to bipolar I disorder. The available literature on treatment of BDII is reviewed. There are virtually no controlled acute treatment trials to direct treatment recommendations, nor is the treatment of BDII addressed in recent treatment guidelines. The most extensive data support lithium (Li) as one treatment group. Striking new findings with lamotrigine (LTG) support its efficacy in BDI acute depression and prophylaxis of rapid cycling BDII. Based on research done, including estimation of safety and tolerability, we chose to evaluate LTG and Li in this pilot study. We propose a randomized, open 16-week clinical trial comparing monotherapy Li versus LTG for sixty acutely depressed BDII patients. A physician and a blinded symptom rater will see patients every two weeks for a total of sixteen weeks. Safeguards are described to maintain patient safety. The primary aim will be to compare the relative treatment

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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effectiveness of LTG versus Li. We hypothesize LTG will be more effective than Li at decreasing depressive symptoms. Secondary aims include assessment of tolerability, the potential of LTG to cause switching into hypomania, quality of life, and patient satisfaction. Measures will include the Hamilton Rating Scale for Depression, Montgomery-Asberg Rating Scale for Depression, Young Mania Rating Scale, Clinical Global Assessment for Bipolar Disorder, and other measures of quality of life, functioning, and physical symptoms and side effects. While full-scale intervention trials are clearly warranted in this population to establish databased recommendations for treatment, it is critical to collect pilot data to properly power and inform the design of a larger trial. This pilot study will provide data addressing the aims and sample size needed for a full-scale intervention trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIPOLAR DISORDER ACROSS THE LIFE SPAN Principal Investigator & Institution: Calabrese, Joseph R.; Professor and Director; Psychiatry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 03-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Bipolar disorder (BPD) affects a minimum of 2.3 million American adults aged 18 and older (1.2% of US population) and in the 5-9% of children with serious emotional disturbances, the prevalence of BPD is unknown, in 1990, BPD in established market economies resulted in 1.7 million years of lost healthy life due to premature death or disability, third only to major depression and schizophrenia. About 15% of patients with BPD commit suicide. The proportion of the NIMH dollar that goes to support research in BPD is less than expected by NIMH leadership, and there are no NIMH-funded BPD research centers. These data suggest there exists an urgent need for an NIMH research center dedicated to BPD research across the life cycle. The proposed Center addresses many of the recommendations in the 1999 "Bridging Science and Services" report by focusing on the utilization of novel longitudinal study designs in complex comorbid groups of patients with BPD from ages 5 through the end of life, as well as by focusing on function and disability, not just symptom improvement. The scientific theme of this Center will be conduct of studies designed to "improve clinical outcomes in underserved population of BPD, including those receiving care within community mental health centers (CMHC), children and adolescents, and adults currently abusing alcohol and/or drugs. The pilot projects include: 1) a single-center psychosocial intervention study designed to develop an efficient and practical way of improving treatment adherence in 166 adults with BPD in a CMHC, 2) a single-center child services project intended to improve the early and accurate recognition of BPD in 615 children and adolescents evaluated at a CMHC, and 3) a six-month, two-center, double-blind, parallel-group comparison of two regimens of combination therapy (lithium/divalproex/lamotrigine versus lithium/divalproex/placebo) for the acute and continuation outpatient management of 90 adult patients with rapid cycling BPD comorbid with alcohol, cannabis, and/or cocaine abuse/dependence at Case Western Reserve University/University Hospitals of Cleveland and a CMHC. This application will be used to build and maintain a network of sites to conduct clinical trials research that concurrently addresses issues of efficacy and effectiveness in BPD across the life cycle. This Developing Center application will be used to develop research partnerships with community settings and grow ongoing relationships, and is intended to lead to an Advanced Center submission in five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Lamotrigine

Project Title: CARDIAC ARREST AND RESUSCITATION--MECHANISMS OF BRAIN INJURY Principal Investigator & Institution: Traystman, Richard J.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Severe hypoxia and complete asphyxia are the most common causes of cardiac arrest in newborn and infant children and can result in cerebral palsy, mental retardation and severe seizures. We have developed a model of asphyxic cardiac arrest in the immature pig that resembles the clinical course of birth asphyxia with selective injury to basal ganglia, cortex and thalamus and with emergence of clinical seizures one day after resuscitation. Our preliminary data indicate that injury to neurons and astrocytes, accompanied by loss of their respective glutamate transporter isoforms, is dense in putamen by 24 hours, whereas neurodegeneration is largely delayed until 48 hours in primary sensorimotor cortex and until 96 hours in thalamic sensory nuclei. Our goal is to understand the mechanism of injury at each step of recovery so that specific therapeutic modalities can be designed to prevent the maturation of injury at each location. We will determine if decreased capacity of the glutamate reuptake transporters occurs during the early hours of reoxygenation when bursts of electrical activity are seen. Mild hypothermia and the glutamate release inhibitor lamotrigine will be used to reduce the overflow of glutamate into the extracellular space as monitored by microdialysis during the first day of recovery. We will determine if suppressing glutamate overflow after resuscitation reduces early neuronal and astrocyte loss in putamen, delayed loss in cortex and thalamus, and neurobehavioral deficits. A component of the delayed neuronal loss in sensorimotor cortex and thalamus may be apoptotic in nature resulting from a) target deprivation secondary to loss of other neurons in the sensorimotor axis, and b) seizures. We will use various morphological and biochemical markers of apoptosis to determine when and where programmed cell death occurs. Phenobarbital loading, as used clinically to suppress birth asphyxia seizures in newborns, will be used to determine the role of seizure activity in the progression of the injury process. The integrative approach of systems neuropathology, immunocytochemical localization, microdialysis and EEG spectral analysis will generate unique mechanistic insights in a model of neonatal brain injury. In mature brain, transgenic mice have been useful for investigating focal ischemic injury, but this approach has not been applied to cardiac arrest. In a model of cardiac arrest and resuscitation in mice, we will test the hypothesis that the combination of neuronal nitric oxide (NO) synthase gene deletion with overexpression of Cu, Zn- superoxide dismutase provides better neuroprotection and improve memory and learning than either gene alteration alone. This study provides a novel approach for understanding the role of NO and oxygen radicals in delayed neuronal injury after cardiac arrest/CPR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDHOOD ABSENCE EPILEPSY: COORDINATING CENTER Principal Investigator & Institution: Cnaan, Avital; Associate Professor of Biostatistics; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: (provided by the applicant): Treatment for Childhood Absence Epilepsy (CAE) is largely empiric. Although there are three efficacious antiepileptic drugs (AEDs) - ethosuximide (ETX), lamotrigine (LTG), valproic acid (VPA) - each has variable success in seizure control, as well as treatment-limiting toxicities. This project is being

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resubmitted as two linked R01 applications. The clinical proposal, "Childhood Absence Epilepsy - Rx, PK/PK, Genetics," (PI: T. Glauser, Co-PI: P. Adamson) is being resubmitted by the Cincinnati Children's Hospital. The objectives of the clinical trial are twofold: a) identify the optimal initial AED in terms of seizure control and lowest toxicity incidence; and b) to determine the clinical, pharmacokinetic and pharmacogenetic factors underlying the inter-individual variation in AED response and toxicity. This linked R01 proposal will establish the Childhood Absence Epilepsy Coordinating Center [CHAECC] at The Children's Hospital of Philadelphia to support this broad, integrated plan to study CAE. A strong and efficient coordinating center is needed in a project of this magnitude and complexity to ensure that the scientific goals are achieved in a timely manner and to a high standard of scientific excellence and data integrity as well as subject safety. The Children's Hospital of Philadelphia (CHOP) has established a highly experienced team to provide this coordinating center function. The aims of the CHAECC are to provide: 1) operational support to implement the protocol; 2) data base and data management for the protocol and the Core's data; 3) biostatistical analyses of the project aims. To meet these goals, the CHAECC will perform start-up activities to implement the project, coordinate all communication activities, oversee adherence to Good Clinical Practice and HIPPA guidelines in protocol implementation, and will work closely with the Scientific Leadership of the study. The CHAECC will develop procedures for data collection, transference, and storage in a secure relational database. The CHAECC will coordinate receipt of video EEG's by Core readers and meetings to achieve consensus in interpretations. It will conduct all statistical analyses and support preparation of reports, manuscripts and presentations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POPULATIONS

COCAINE

PHARMACOTHERAPIES

FOR

COMORBID

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 30-SEP-1999; Project End 31-AUG-2004 Summary: This Center for Medications Development (MDU) has a theme of cocaine pharrnacotherapy with eight outpatient randomized clinical trials in four comorbid populations: depressed, opioid dependent (methadone and LAAM), and those with brain perfusion defects. These eight trials are arranged sequentially with four during months 1 to 30 (trials #1,3,5,7) and four during months 31-60 (trials #2,4,6,8). Trials 1 and 2 are "Bupropion & sertraline for depression and cocaine dependence" including 60 patients each in randomized, placebo controlled 12 week trials - bupropion (#1) and sertraline (#2). Trials 3 and 4 are "Disulfiram & GABA agonists with LAAM for cocaine" including 60 patients in randomized, placebo controlled 12 week trials of first disulfiram (#3) and then one of the GABA agents tiagabine or baclofen (#4). Trial 5 in methadone patients will involve tiagabine and baclofen in an 8 week screening study that allocates 60 subjects to five cells including placebo and two doses of each agent during the first 30 months. Trial 6 uses a similar screening design involving glutamate antagonists acamprosate and lamotrigine in months 31-60. Trials 7 and 8 are "Clopidogrel & isradipine for brain perfusion defects" involving blood flow neuroimaging in two different groups of 60 patients with these cocaine-induced defects as an outcome. These 12 week trials of first clopidogrel (#7) and then isradipine (#8) include 4 weeks residential with an 8 week outpatient follow-up. Overall, about 500 patients will be studied in this Center and nine different agents in either screening (trials 5 & 6) or full Phase ll trials.

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

Project Title: EFFECT OF AGE ON GLUCURONIDATION OF ANTIEPILEPTIC DRUGS Principal Investigator & Institution: Remmel, Rory P.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: The pharmacokinetics and metabolism of antiepileptic drugs (AEDs) in the eldedy population is poorly studied, particularly in the old and old-old (patients >-75), that comprise the fastest growing population group in the U.S. Glucuronidation is a major metabolic pathway for several AEDs including lamotrigine, oxcarbazepine, and valproic acid. In this project, the pharmacokinetics of lamotrigine and valproic acid will be studied in younger adults (ages 18-50) and elderly patients (ages 65-74 and >-75) by a novel stableisotope technique. An innovative formulation of stable-labeled isotope of lamotrigine will be prepared in solutions of 2-hydroxypropyl-beta-cyclodextrin in water. Studies on the glucuronidation of this drug as well as valproic acid, the major oxidative metabolite of phenytoin, p-HPPH and the active form of oxcarbazepine, 10hydroxy carbamazepine, will be conducted with a pre-existing human liver microsomal tissue bank that has been obtained from elderly donors. The individual glucuronosyltransferase enzymes responsible for the glucuronidation of these AEDs and metabolites will be identified by kinetic studies in microsomes and screening with cloned, expressed enzymes. These studies will be done to help predict drug interactions that may occur between AEDs and between AEDs and other drugs that are glucuronidated. Individual drug interactions will be studied in vitro in microsomes prepared from elderly donors. The goal of this project is to determine if AED glucuronidation is affected by age and to develop dosing guidelines for the major elderly age groups: the young-old, the old, and the old-old. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPILEPSY CLINICAL RESEARCH PROGRAM Principal Investigator & Institution: Leppik, Ilo E.; Professor; Neurology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUL-1980; Project End 31-AUG-2007 Summary: (provided by applicant): The incidence of epilepsy rises rapidly after age 60 with a reported prevalence of 1.48% for persons over 75. Pharmacoepidemiologic studies performed during the current P50 show that the prevalence of anti epileptic drug (AED) use is approximately 2% among the community-dwelling elderly (Health Care Finance Administration data set (n = ~12,000/yr) and approximately 9% among nursing home residents (Beverly data set). Clearly, the absolute number of elderly using AEDs will increase greatly in the near future, but very little is known about the safe and effective use of these powerful modulators of neurological functioning in this population. The goal of this 5-year program project is to increase our knowledge of the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacoepidemiology (PE) of AEDs in the elderly. This information is critical for the design of appropriate controlled trials and the development of evidence-based guidelines for this population. We will investigate these issues using a variety of approaches including hepatic microsomes in vitro liver, stable labeled isotopes in volunteers, non-linear mixed effect modeling (NOME) and application of estimated AED concentrations to outcomes in a large nursing home population. Extensive genotyping of CYP3A4/5 and initial investigation

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of genetic and racial factors in AED metabolism will be carried out. The PK characteristics of carbamazepine (CBZ), valproic acid (VPA), lamotrigine (LTG), and topiramate (TPM) in elderly patients will be determined using stable labeled intravenous preparations developed by our group. NONMEM analysis will be performed using clinical data from Minnesota, Atlanta, Miami, and the national Veterans Administration Cooperative Study. These 3 sites will provide the largest group of elderly persons with epilepsy ever studied and have enough power to test the hypotheses. Findings regarding phenytoin (PHT), CBZ and VPA PK from the current and proposed P50 will be applied to dose, weight, and to outcome measures in the extant Beverly Nursing Home database. This will allow us to estimate AED concentrations in this population and determine prevalence and type of adverse events associated with high, middle, or low concentrations. The information obtained from this multi-pronged effort will have profound impact on the use of AEDs in the elderly. 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.; Assistant Professor of Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 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

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Lamotrigine

Project Title: THERAPY

HIPPOCAMPAL

FUNCTION

DURING

CORTICOSTEROID

Principal Investigator & Institution: Brown, E Sherwood.; Assistant Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract) This Mentored Clinical Scientist Development Award (MCSDA) application defines a training program to facilitate the development of the Pl as an independent researcher in the area of mood disorders. The educational activities outlined will enable the Pl to explore the biological basis of corticosteroid effects on brain function. During the course of this award, Dr. A. John Rush will serve as the PI's mentor. Additional experts providing instruction and training include: Drs. Frederick Petty (clinical trials), Bruce S. McEwen (glucocorticoids and the hippocampus), and Alan Frol and C. Munro Cullum (cognitive neuroscience). Measurement of hippocampal volumes from MRI scans will be performed by Dr. John Csernansky's group at Washington University. The training entails increasing the PI's knowledge of neuropsychological testing and clinical research methodology. The Pl plans to use cognitive testing to develop a paradigm in humans for exploring pharmacologic interventions which may prevent or reverse hippocampal changes associated with corticosteroids. In order to achieve the stated training goals, the Pl has developed a program that includes didactic courses, tutorials, and a research project. The proposed project will afford a hands-on experience, reinforcing the information and techniques learned through mentoring and classroom environments. The Pl will first examine memory, mood, and hippocampal volume in asthma and rheumatoid arthritis patients receiving chronic oral prescription corticosteroid therapy, a population the Pl has actively researched for over three years. In animals, agents which inhibit the release of glutamate appear to prevent and reverse hippocampal damage secondary to corticosteroids. Thus, the first experiment in the training plan will be followed by a clinical trial of the glutamate release inhibitor, lamotrigine, to determine if neurocognitive changes associated with corticosteroids can be reversed in humans. Through this award, the Pl will extend his previous research experience by adding new skills and knowledge which will be used for investigations at the interface of neuroscience and clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LAMOTRIGINE IN TREATMENT OF PAINFUL HIV ASSOCIATED SENSORY NEUROPATHY Principal Investigator & Institution: Mcarthur, Justin C.; Professor of Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: This is a phase II, multicenter, randomized, double-blind, placebo- controlled trial of the safety, tolerability and efficacy of pain relief of lamotrigine for HIVassociated sensory neuropathy. Peripheral neuropathy is a common complication of HIV infection. HIV-associated sensory neuropathy is a common form of neuropathy in advanced HIV infection. Approximately 30% of patients with AIDS develop HIVassociated sensory neuropathy. Symptoms can be painful and can greatly impact on the activities of daily living as well as the quality of life. A direct viral etiology has been postulated as a causative agent. Certain antiretrovirals (ddI, ddC, d4T) are also known to cause neuropathy in this patient population. Therapeutic treatment of painful sensory neuropathy has been difficult. Current management involves the use of sympomatic or

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pain-modifying agents. Symptomatic relief with tricyclic antidepressants, non-steroidal anti-inflammatory agents, topical capsaicin or opiates has been limited. A trial is currently underway with a potentially restorative agent, nerve growth factor. Lamotrigine is a newly approved anti-convulsant which blocks voltage sensitive sodium channels, resulting in inhibition of glutamate and aspartate release. Lamotrigine has similar efficacy in maximal electro- shock models to carbamazepine and phenytoin, both of which have proven efficacious for the treatment of painful diabetic neuropathy. To date, there have only been anectodal reports of the efficacy of lamotrigine for treatment of HIV-associated sensory neuropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL PHARMACOTHERAPIES FOR OPIOID WITHDRAWAL Principal Investigator & Institution: Walsh, Sharon L.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 30-JUN-2003 Summary: The physical dependence and withdrawal syndrome produced by chronic opioid use represents a significant hurdle for those patients seeking treatment. Available pharmacological detoxification agents are circumscribed and the use of some are rigorously regulated. Recent advances in neurobiology suggest that central noradrenergic and glutamateric processes are intimately involves in the development of opioid physical dependence and withdrawal. These studies will evaluate the ability of four novel medications whose effects are exerted through these neurotransmitter systems for their ability to attenuate or block opioid withdrawal using controlled laboratory procedures. The targeted study drugs are 1) lofexidine, an alpha2-adrenergic receptor agonist, 2) memantine, a non competitive NMDA receptor antagonist, 3) lamotrigine, a NA+ channel blocker with indirect glutamate antagonist properties, and 4) acamprosate, a post-synaptic glutamate antagonist; each drug will be evaluated in a separate study. Participants will be healthy adult volunteers who are physically dependent on opioids (n=10/study). Participants will be stabilized as outpatients for a period of at least 4 weeks on methadone (30 mg p.o./day) prior to inpatient admission. These studies will employ a model of antagonist precipitated withdrawal; this method has been shown to replicable, generalizable to spontaneous withdrawal, and welltolerated by opioid-dependent patients. The effects of acute pretreatment with each test agent (placebo and 3 active doses) on the subjective and physiological response to intramuscular challenge with placebo or naloxone (0.` & 0.3 mg) will be evaluated during controlled experimental sessions. Using this design, the safety and pharmacodynamic profile of each novel drug will be characterized alone, and the efficacy of those agents to suppress withdrawal will be evaluated over a range of test doses and two different withdrawal intensities. These studies will provide new information about the safety and pharmacodynamic effects of these novel agents, may provide some insight into the neural mechanisms which underlie opioid physical dependence in humans, and, most importantly, will serve as a first step in the development of new pharmacotherapeutic strategies for the treatment of opioid withdrawal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ONTOGENY OF DRUG BIOACTIVATION AND IDIOSYNCRATIC ADRS Principal Investigator & Institution: Leeder, James S.; Chief; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108

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Lamotrigine

Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Idiosyncratic adverse drug reactions (ADRs) are relatively rare, but potentially life-threatening events in which the determinants of susceptibility (largely unknown) are thought to be unique to the individual experiencing the adverse event. They can occur throughout the age spectrum but tend to be underemphasized in the pediatric literature yet children appear to be at increased risk for certain idiosyncratic ADRs such as valproate hepatotoxicity and cutaneous reactions to lamotrigine. An important step in the development of an idiosyncratic ADR appears to be biotransformation of the implicated drug to a chemically reactive metabolite ("bioactivation") that is capable of binding to cellular macromolecules and producing cell death directly or indirectly through initiation of an immune response. Although developmental changes in drug metabolizing enzymes such as the cytochromes P450 (CYPs) and glucuronosyl transferase (UGTs) have been characterized in children, little is known about the ontogeny of drug bioactivation as children grow and develop. Using biomarkers of acetaminophen (APAP), carbamazepine (CBZ) and valproic acid (VPA) bioactivation (and detoxification) in vivo, the goals of this research program are 1. to characterize the ontogeny of the drug bioactivation biomarkers in vivo and in vitro and 2. to identify the pharmacogenetic determinants of interindividual variability in APAP, CBZ and VPA biomarker expression during growth and development. To achieve these goals, two longitudinal "bioactivation" phenotyping studies will be conducted 1. in healthy children following a single test dose of APAP (15 mg/kg as Tylenol(r) alcoholfree solution, 80mg/0.8ml) and 2. in epileptic children routinely receiving CBZ or VPA for medical management of their disease involving NICHD PPRU sites in Kansas City, MO, Shreveport, LA, and Little Rock, AR. For each study, urine is collected overnight and analyzed for the presence of parent drug, "non-toxic" metabolites and conjugated l metabolites of candidate reactive metabolites. Specific urinary metabolite ratios will be used to determine the changes in reactive metabolic "burden" that occur during growth and development with specific reference to changes in CYP activities identified in longitudinal phenotyping studies currently underway. Paired DNA samples from the extremes of the population distributions will be subjected to a concerted search by DNA sequencing and fragment analysis for single nucleotide polymorphisms (SNPs) that contribute to inter-individual variability in drug bioactivation. It is anticipated that the results of this program will allow critical periods of increased bioactivation and thus, potential vulnerability to idiosyncratic ADRs, to be identified for subsequent prospective investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOEPIDEMIOLOGY OF THE ANTIEPILEPTIC DRUGS Principal Investigator & Institution: Birnbaum, Angela K.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: The incidence of epilepsy rises rapidly after age 60, and many elderly are being treated with phenytoin (PHT), carbamazepine (CBZ) and valproic acid (VPA). These older antiepileptic drugs (AEDs) have many shortcomings including complex metabolism by the cytochrome P450 and glucuronidation enzyme systems and have been shown to be inducers and inhibitors in these systems. This makes them prone to many drug interactions involving both clearance and protein binding. This is a multifaceted issue; AED efficacy and toxicity may be altered by co-medications, and AEDs can affect the efficacy and toxicity of co-medications. Because an elderly patient uses an average of 6 medications, the risk of medication interactions in this age group

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with these older AEDs is very high. Three newer AEDs, lamotrigine (LTG), topiramate (TPM) and levetiracetam (LEV) appear to have more favorable drug-drug interaction profiles; all have low protein binding and fewer or no metabolic interactions. However, these newer drugs have not been studied sufficiently in the eldedy and more detailed information regarding the pharmacokinetio and pharmacodynamic properties of these is needed. The difficulty in obtaining blood samples from this population makes inclusion in standard pharrnacokinetic studies difficult. This project will use nonlinear mixed effects model (NONMEM) that employs both pharmacokinetics and statistics will be used to determine pharrnacokinetic parameters of these three new drugs. This powerful method allows the use of routinely collected data to be used and avoids the risks and expense encountered in intensive pharmacokinetic studies. With this method, not only can the drug clearance be determined for a population, but it can also be determined for an individual. Factors (age, race, gender, smoking, etc.) that affect drug clearance can also be determined. In addition, the relationship between serum drug concentration and seizure type will be determined for LTG, TPM, and LEV. We will have access to approximately 450 persons >65 years of age receiving LTG, 420 receiving TPM and 337 receiving LEV from several active epilepsy practices in 3 cities (Minneapolis, Miami, Atlanta) and data from more than 1500 younger adults on each of these AEDs. In addition we will use our tools to analyze data from the ongoing perspective VA cooperative study of LTG projected to enroll 240 subjects receiving LTG as initial treatment. The VA data will determine the relationship between drug concentrations and adverse events and seizure frequency for LTG providing both pharmacokinetic and pharmacodynamic information in the elderly. This project along with Projects 1 and 2 will provide pharmacokinetic data and identify and quantitate the factors that influence the pharmacokinetics of LTG, LEV, and TPM. This information can be used to guide dosing requirements needed to obtain target serum concentrations in the elderly to achieve seizure control and avoid drug toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GSK3BETA BY MOOD STABILIZERS Principal Investigator & Institution: Li, Xiaohua; Psychiatry & Behav Neurobiol; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2004; Project Start 05-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Bipolar disorder is a severe mental disorder with limited pharmacological treatment because the pathophysiology of this severe mental illness is poorly understood. No definitive mechanism of action of available mood stabilizers has been identified, which limits the development of new mood stabilizing agents. Extensive studies in vitro and in cultured cells have shown that lithium and valproate modulate glycogen synthase kinase-3beta (GSK3beta), a unique protein kinase that is under inhibitory control by several signaling systems. Although GSK3beta is a prime candidate therapeutic target of mood stabilizers, there is limited evidence of in vivo regulation of GSK3beta by mood stabilizers, and its relevance to the therapeutic effects of mood stabilizers in bipolar disorder remains to be established. The objective of this project is to identify the in vivo regulatory effects of the available mood stabilizers on GSK3beta and the associated signaling systems, specifically the upstream PI3K/Akt signaling pathway and the downstream target transcription factor CREB. The central hypothesis for the proposed research is that GSK3beta is a central component of the mechanisms of action of lithium and other mood stabilizers in vivo. The Specific Aim of this two-year project is to test the hypothesis that lithium and other anticonvulsant mood stabilizers modulate GSK3beta in the brain and in peripheral lymphocytes of

14

Lamotrigine

mice. The working hypotheses include that chronic treatments with therapeutically relevant doses of lithium, valproate, and lamotrigine inhibit GSK3beta in mouse brain, the mechanisms of action of the mood stabilizers may involve regulating GSK3beta or the PI3K/Akt signaling pathway, with a common consequence of regulating the transcription factor CREB, and the effect of lamotrigine on GSK3beta may be related to its blocking effects on glutamate release. If GSK3beta represents an important therapeutic target of mood stabilizers, it is important to test if changes occurring in mouse brain are also detectable in mouse lymphocytes, since this will be a basis for future testing of similar changes in humans. This study will apply knowledge obtained from in vitro studies of GSK3beta to in vivo studies of mouse brain, and for the first time proposes to identify the in vivo actions of mood stabilizers on GSK3beta and the associated PI3K/Akt signaling pathway as potential therapeutic targets of mood stabilizers. The proposed research is expected to provide significant new insight into the pathophysiology and treatment of bipolar disorder. The data obtained from this proposal will be used to support a future R01 grant application to achieve our long-term goal of understanding the pathophysiology and improving the treatment of bipolar disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “lamotrigine” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lamotrigine in the PubMed Central database: •

Agranulocytosis associated with lamotrigine. by de Camargo OA, Bode H.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27855

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

A comparison of monotherapy with lamotrigine or carbamazepine in patients with newly diagnosed partial epilepsy. Author(s): Nieto-Barrera M, Brozmanova M, Capovilla G, Christe W, Pedersen B, Kane K, O'Neill F; Lamictal vs. Carbamazepine Study Group. Source: Epilepsy Research. 2001 August; 46(2): 145-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11463516

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A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure. Author(s): Gillham R, Kane K, Bryant-Comstock L, Brodie MJ. Source: Seizure : the Journal of the British Epilepsy Association. 2000 September; 9(6): 375-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10985991

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A double-blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid levels and clinical parameters. Author(s): Ryberg H, Askmark H, Persson LI. Source: Acta Neurologica Scandinavica. 2003 July; 108(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807386

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A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. Author(s): Calabrese JR, Suppes T, Bowden CL, Sachs GS, Swann AC, McElroy SL, Kusumakar V, Ascher JA, Earl NL, Greene PL, Monaghan ET. Source: The Journal of Clinical Psychiatry. 2000 November; 61(11): 841-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11105737

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A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. Author(s): Barbosa L, Berk M, Vorster M. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 403-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716240

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A pharmacoepidemiologic study of factors influencing the outcome of treatment with lamotrigine in chronic epilepsy. Author(s): Wong IC, Mawer GE, Sander JW, Lhatoo SD. Source: Epilepsia. 2001 October; 42(10): 1354-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737172

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A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Author(s): Calabrese JR, Bowden CL, Sachs G, Yatham LN, Behnke K, Mehtonen OP, Montgomery P, Ascher J, Paska W, Earl N, DeVeaugh-Geiss J; Lamictal 605 Study Group. Source: The Journal of Clinical Psychiatry. 2003 September; 64(9): 1013-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628976

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A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Author(s): Bowden CL, Calabrese JR, Sachs G, Yatham LN, Asghar SA, Hompland M, Montgomery P, Earl N, Smoot TM, DeVeaugh-Geiss J; Lamictal 606 Study Group. Source: Archives of General Psychiatry. 2003 April; 60(4): 392-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695317

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A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. Author(s): Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA, Luckenbaugh DA, Cora-Ocatelli G, Leverich GS, Post RM. Source: Journal of Clinical Psychopharmacology. 2000 December; 20(6): 607-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106131

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A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial Seizure Study Group. Author(s): Duchowny M, Pellock JM, Graf WD, Billard C, Gilman J, Casale E, Womble G, Risner M, Manasco P. Source: Neurology. 1999 November 10; 53(8): 1724-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10563619

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A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy. Author(s): Simpson DM, Olney R, McArthur JC, Khan A, Godbold J, Ebel-Frommer K. Source: Neurology. 2000 June 13; 54(11): 2115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10851374

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A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder. Author(s): Sierra M, Phillips ML, Ivin G, Krystal J, David AS. Source: Journal of Psychopharmacology (Oxford, England). 2003 March; 17(1): 103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680746

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A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy. Author(s): Crawford P, Brown S, Kerr M; Parke Davis Clinical Trials Group. Source: Seizure : the Journal of the British Epilepsy Association. 2001 March; 10(2): 10715. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407953

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Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca2+ channel currents. Author(s): Hainsworth AH, McNaughton NC, Pereverzev A, Schneider T, Randall AD. Source: European Journal of Pharmacology. 2003 April 25; 467(1-3): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706458

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Acute granulomatous interstitial nephritis and colitis in anticonvulsant hypersensitivity syndrome associated with lamotrigine treatment. Author(s): Fervenza FC, Kanakiriya S, Kunau RT, Gibney R, Lager DJ. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 November; 36(5): 1034-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11054362

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Acute hepatitis after lamotrigine administration. Author(s): Sauve G, Bresson-Hadni S, Prost P, Le Calvez S, Becker MC, Galmiche J, Carbillet JP, Miguet JP. Source: Digestive Diseases and Sciences. 2000 September; 45(9): 1874-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11052335

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Adding valproate to lamotrigine: a study of their pharmacokinetic interaction. Author(s): Kanner AM, Frey M. Source: Neurology. 2000 August 22; 55(4): 588-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953201

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Add-on lamotrigine treatment in children and young adults with severe partial epilepsy: an open, prospective, long-term study. Author(s): Parmeggiani L, Belmonte A, Ferrari AR, Perucca E, Guerrini R. Source: Journal of Child Neurology. 2000 October; 15(10): 671-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11063081

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Adjunctive lamotrigine treatment for major depression. Author(s): Maltese TM. Source: The American Journal of Psychiatry. 1999 November; 156(11): 1833. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10553753

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Adverse event monitoring in lamotrigine patients: a pharmacoepidemiologic study in the United Kingdom. Author(s): Wong IC, Mawer GE, Sander JW. Source: Epilepsia. 2001 February; 42(2): 237-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240596

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Aggression in dementia with lamotrigine treatment. Author(s): Devarajan S, Dursun SM. Source: The American Journal of Psychiatry. 2000 July; 157(7): 1178. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10873935

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Agranulocytosis associated with lamotrigine in a patient with low-grade glioma. Author(s): Fadul CE, Meyer LP, Jobst BC, Cornell CJ, Lewis LD. Source: Epilepsia. 2002 February; 43(2): 199-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903469

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Agranulocytosis associated with lamotrigine. Author(s): Solvason HB. Source: The American Journal of Psychiatry. 2000 October; 157(10): 1704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11007735

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An active-control trial of lamotrigine monotherapy for partial seizures. Author(s): Panayiotopoulos CP. Source: Neurology. 2000 February 8; 54(3): 777. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10680834

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An active-control trial of lamotrigine monotherapy for partial seizures. Author(s): Gilliam F, Vazquez B, Sackellares JC, Chang GY, Messenheimer J, Nyberg J, Risner ME, Rudd GD. Source: Neurology. 1998 October; 51(4): 1018-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781523

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An open longitudinal study of patients with bipolar rapid cycling treated with lithium or lamotrigine for mood stabilization. Author(s): Walden J, Schaerer L, Schloesser S, Grunze H. Source: Bipolar Disorders. 2000 December; 2(4): 336-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11252647

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Analgesic effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers. Author(s): Webb J, Kamali F. Source: Pain. 1998 June; 76(3): 357-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9718254

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Antiglutamatergic therapy in Alzheimer's disease--effects of lamotrigine. Short communication. Author(s): Tekin S, Aykut-Bingol C, Tanridag T, Aktan S. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1998; 105(2-3): 295-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9660108

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Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Author(s): Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Source: Archives of General Psychiatry. 2000 March; 57(3): 270-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10711913

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Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. Author(s): Dursun SM, Deakin JF. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 297301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11769825

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Behavioral and cognitive effects of lamotrigine. Author(s): Meador KJ, Baker GA. Source: Journal of Child Neurology. 1997 November; 12 Suppl 1: S44-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9429130

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Beneficial behavioural effects of lamotrigine in traumatic brain injury. Author(s): Pachet A, Friesen S, Winkelaar D, Gray S. Source: Brain Injury : [bi]. 2003 August; 17(8): 715-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850956

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Bidirectional interaction of valproate and lamotrigine in healthy subjects. Author(s): Anderson GD, Yau MK, Gidal BE, Harris SJ, Levy RH, Lai AA, Wolf KB, Wargin WA, Dren AT. Source: Clinical Pharmacology and Therapeutics. 1996 August; 60(2): 145-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8823232

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Lamotrigine

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Carbamazepine and lamotrigine in healthy volunteers: relevance to early tolerance and clinical trial dosage. Author(s): Hamilton MJ, Cohen AF, Yuen AW, Harkin N, Land G, Weatherley BC, Peck AW. Source: Epilepsia. 1993 January-February; 34(1): 166-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8422853

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Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction? Author(s): Besag FM, Berry DJ, Pool F, Newbery JE, Subel B. Source: Epilepsia. 1998 February; 39(2): 183-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9577998

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Cellular and molecular actions of lamotrigine: Possible mechanisms of efficacy in bipolar disorder. Author(s): Xie X, Hagan RM. Source: Neuropsychobiology. 1998 October; 38(3): 119-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9778599

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Characterization of drug-specific T cells in lamotrigine hypersensitivity. Author(s): Naisbitt DJ, Farrell J, Wong G, Depta JP, Dodd CC, Hopkins JE, Gibney CA, Chadwick DW, Pichler WJ, Pirmohamed M, Park BK. Source: The Journal of Allergy and Clinical Immunology. 2003 June; 111(6): 1393-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789244

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Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Author(s): Lunardi G, Leandri M, Albano C, Cultrera S, Fracassi M, Rubino V, Favale E. Source: Neurology. 1997 June; 48(6): 1714-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9191794

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Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine and felbamate. Author(s): Battino D, Estienne M, Avanzini G. Source: Clinical Pharmacokinetics. 1995 November; 29(5): 341-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8582119

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Clinical pharmacokinetics of newer antiepileptic drugs. Lamotrigine, vigabatrin, gabapentin and oxcarbazepine. Author(s): Elwes RD, Binnie CD. Source: Clinical Pharmacokinetics. 1996 June; 30(6): 403-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792055

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Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios. Author(s): Lathers CM, Schraeder PL, Claycamp HG. Source: Journal of Clinical Pharmacology. 2003 May; 43(5): 491-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751270

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Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Author(s): Obrocea GV, Dunn RM, Frye MA, Ketter TA, Luckenbaugh DA, Leverich GS, Speer AM, Osuch EA, Jajodia K, Post RM. Source: Biological Psychiatry. 2002 February 1; 51(3): 253-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11839368

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Clinical studies on the use of lamotrigine in bipolar disorder. Author(s): Calabrese JR, Rapport DJ, Shelton MD, Kujawa M, Kimmel SE. Source: Neuropsychobiology. 1998 October; 38(3): 185-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9778607

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Clinical use of lamotrigine. Author(s): Betts T. Source: Seizure : the Journal of the British Epilepsy Association. 1992 March; 1(1): 3-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1344317

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Clinically relevant reduction of lamotrigine concentrations by carbamazepine. Author(s): Koch HJ, Szecsey A, Vogel M. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 February; 18(1): 42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648898

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Clozapine plus lamotrigine in treatment-resistant schizophrenia. Author(s): Dursun SM, McIntosh D, Milliken H. Source: Archives of General Psychiatry. 1999 October; 56(10): 950. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10530638

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Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Author(s): Aldenkamp AP. Source: Neurology. 2000 January 11; 54(1): 271-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636175

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Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Author(s): Lhatoo SD, Sander JW, Wong IC. Source: Neurology. 2000 January 11; 54(1): 270-1; Author Reply 271-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636174

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Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Author(s): Martin R, Kuzniecky R, Ho S, Hetherington H, Pan J, Sinclair K, Gilliam F, Faught E. Source: Neurology. 1999 January 15; 52(2): 321-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9932951

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Cognitive impairment associated with lamotrigine. Author(s): Bouman WP, Pinner G, Johnson H. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1997 April; 170: 388-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9246264

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Combination vigabatrin and lamotrigine therapy for intractable epilepsy. Author(s): Schapel GJ, Black AB, Lam EL, Robinson M, Dollman WB. Source: Seizure : the Journal of the British Epilepsy Association. 1996 March; 5(1): 51-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8777553

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Comment: lamotrigine dosing. Author(s): Manasco PK. Source: The Annals of Pharmacotherapy. 1995 November; 29(11): 1173. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8573970

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Comparison of lamotrigine and valproate with respect to quality of life. Author(s): Reed RC, Giordano S. Source: Epilepsy & Behavior : E&B. 2003 February; 4(1): 88-9; Reply 89-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12609233

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Comparison of the effects of vigabatrin, lamotrigine, and topiramate on quantitative EEGs in patients with epilepsy. Author(s): Neufeld MY, Kogan E, Chistik V, Korczyn AD. Source: Clinical Neuropharmacology. 1999 March-April; 22(2): 80-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10202602

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Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers. Author(s): Wootton R, Soul-Lawton J, Rolan PE, Sheung CT, Cooper JD, Posner J. Source: British Journal of Clinical Pharmacology. 1997 January; 43(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9056048

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Concentration--effect and concentration--toxicity relations with lamotrigine: a prospective study. Author(s): Kilpatrick ES, Forrest G, Brodie MJ. Source: Epilepsia. 1996 June; 37(6): 534-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8641229

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Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child. Author(s): Rambeck B, Kurlemann G, Stodieck SR, May TW, Jurgens U. Source: European Journal of Clinical Pharmacology. 1997; 51(6): 481-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9112063

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Concerns regarding lamotrigine and breast-feeding. Author(s): Liporace J, Kao A, D'Abreu A. Source: Epilepsy & Behavior : E&B. 2004 February; 5(1): 102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751214

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Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures. Author(s): Boas J, Dam M, Friis ML, Kristensen O, Pedersen B, Gallagher J. Source: Acta Neurologica Scandinavica. 1996 October; 94(4): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8937535

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Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation. Author(s): Manganotti P, Bongiovanni LG, Zanette G, Turazzini M, Fiaschi A. Source: Epilepsia. 1999 March; 40(3): 316-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10080512

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Cost-effectiveness model of adjunctive lamotrigine for the treatment of epilepsy. Author(s): Markowitz MA, Mauskopf JA, Halpern MT. Source: Neurology. 1998 October; 51(4): 1026-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781524

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Cost-effectiveness model of adjunctive lamotrigine for the treatment of epilepsy. Author(s): Heaney DC, Sander JW. Source: Neurology. 1999 August 11; 53(3): 657-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10449148

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Could lamotrigine be useful in status epilepticus? A case report. Author(s): Pisani F, Gallitto G, Di Perri R. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1991 September; 54(9): 845-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1955910

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Determination of lamotrigine in biologic materials by a simple and rapid liquid chromatographic method. Author(s): Ren S, Scheuer ML, Zheng W. Source: Therapeutic Drug Monitoring. 1998 April; 20(2): 209-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9558136

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Determination of lamotrigine in human plasma by high-performance liquid chromatography. Author(s): Angelis-Stoforidis P, Morgan DJ, O'Brien TJ, Vajda FJ. Source: J Chromatogr B Biomed Sci Appl. 1999 April 30; 727(1-2): 113-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10360429

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Determination of lamotrigine in human serum by liquid chromatography. Author(s): Vidal E, Pascual C, Pou L. Source: J Chromatogr B Biomed Sci Appl. 1999 December 24; 736(1-2): 295-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10677010

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Determination of lamotrigine simultaneously with carbamazepine, carbamazepine epoxide, phenytoin, phenobarbital, and primidone in human plasma by SPME-GCTSD. Author(s): Queiroz ME, Silva SM, Carvalho D, Lancas FM. Source: Journal of Chromatographic Science. 2002 April; 40(4): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004942

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Determination of lamotrigine, carbamazepine and carbamazepine epoxide in human serum by gas chromatography mass spectrometry. Author(s): Hallbach J, Vogel H, Guder WG. Source: Eur J Clin Chem Clin Biochem. 1997 October; 35(10): 755-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9368793

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Differential cognitive and behavioral effects of carbamazepine and lamotrigine. Author(s): Meador KJ, Loring DW, Ray PG, Murro AM, King DW, Perrine KR, Vazquez BR, Kiolbasa T. Source: Neurology. 2001 May 8; 56(9): 1177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11342682

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Disabling erratic myoclonus during lamotrigine therapy with high serum level-report of two cases. Author(s): Janszky J, Rasonyi G, Halasz P, Olajos S, Perenyi J, Szucs A, Debreczeni T. Source: Clinical Neuropharmacology. 2000 March-April; 23(2): 86-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10803798

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Disabling tremor after lamotrigine with sodium valproate. Author(s): Reutens DC, Duncan JS, Patsalos PN. Source: Lancet. 1993 July 17; 342(8864): 185-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8101290

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Does lamotrigine influence valproate concentrations? Author(s): Mataringa MI, May TW, Rambeck B. Source: Therapeutic Drug Monitoring. 2002 October; 24(5): 631-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352935

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Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group. Author(s): Brodie MJ, Richens A, Yuen AW. Source: Lancet. 1995 February 25; 345(8948): 476-9. Erratum In: Lancet 1995 March 11; 345(8950): 662. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7710545

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Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. Author(s): Binnie CD, Debets RM, Engelsman M, Meijer JW, Meinardi H, Overweg J, Peck AW, Van Wieringen A, Yuen WC. Source: Epilepsy Research. 1989 November-December; 4(3): 222-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2612495

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Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures. Author(s): Schapel GJ, Beran RG, Vajda FJ, Berkovic SF, Mashford ML, Dunagan FM, Yuen WC, Davies G. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1993 May; 56(5): 448-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8505632

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Double-blind, placebo-controlled, crossover study of lamotrigine in treatmentresistant generalised epilepsy. Author(s): Beran RG, Berkovic SF, Dunagan FM, Vajda FJ, Danta G, Black AB, Mackenzie R. Source: Epilepsia. 1998 December; 39(12): 1329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9860069

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Drug-induced pseudolymphoma secondary to lamotrigine. Author(s): Pathak P, McLachlan RS. Source: Neurology. 1998 May; 50(5): 1509-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9596028

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Dysgeusia in epileptic patients treated with lamotrigine: report of three cases. Author(s): Avoni P, Contin M, Riva R, Albani F, Liguori R, Baruzzi A. Source: Neurology. 2001 October 23; 57(8): 1521. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673609

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Economic analysis of epilepsy treatment: a cost minimization analysis comparing carbamazepine and lamotrigine in the UK. Author(s): Shakespeare A, Simeon G. Source: Seizure : the Journal of the British Epilepsy Association. 1998 April; 7(2): 119-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9627202

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Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures. Author(s): McCabe PH, McNew CD, Michel NC. Source: Archives of Neurology. 2001 August; 58(8): 1264-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11493167

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Effect of felbamate on the pharmacokinetics of lamotrigine. Author(s): Colucci R, Glue P, Holt B, Banfield C, Reidenberg P, Meehan JW, Pai S, Nomeir A, Lim J, Lin CC, Affrime MB. Source: Journal of Clinical Pharmacology. 1996 July; 36(7): 634-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8844446

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Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis. Author(s): Marciani MG, Spanedda F, Bassetti MA, Maschio M, Gigli GL, Mattia D, Bernardi G. Source: British Journal of Clinical Pharmacology. 1996 November; 42(5): 621-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8951194

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Effect of lamotrigine on mood and cognition in patients receiving chronic exogenous corticosteroids. Author(s): Brown ES, Frol A, Bobadilla L, Nejtek VA, Perantie DC, Dhillon H. Source: Psychosomatics. 2003 May-June; 44(3): 204-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724501

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Effect of lamotrigine on plasma GABA levels in healthy humans. Author(s): Shiah IS, Yatham LN, Gau YC, Baker GB. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 419-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691776

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Effect of lamotrigine treatment in epileptic psychosis. Author(s): De Leon OA, Furmaga KM. Source: Journal of Clinical Psychopharmacology. 1999 April; 19(2): 186-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10211924

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Effectiveness of lamotrigine in children with paroxysmal kinesigenic choreoathetosis. Author(s): Uberall MA, Wenzel D. Source: Developmental Medicine and Child Neurology. 2000 October; 42(10): 699-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11085299

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Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study. Author(s): D'Andrea G, Granella F, Cadaldini M, Manzoni GC. Source: Cephalalgia : an International Journal of Headache. 1999 January; 19(1): 64-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099862

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Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy. Author(s): Placidi F, Marciani MG, Diomedi M, Scalise A, Pauri F, Giacomini P, Gigli GL. Source: Acta Neurologica Scandinavica. 2000 August; 102(2): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10949523

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Effects of lamotrigine on pain-induced chemo-somatosensory evoked potentials. Author(s): Klamt JG, Posner J. Source: Anaesthesia. 1999 August; 54(8): 774-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460530

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Effects of lamotrigine on the 5-HT1A receptor function in healthy human males. Author(s): Shiah IS, Yatham LN, Lam RW, Zis AP. Source: Journal of Affective Disorders. 1998 May; 49(2): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9609681

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Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects. Author(s): Ebert U, Thong NQ, Oertel R, Kirch W. Source: European Journal of Clinical Pharmacology. 2000 July; 56(4): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954343

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Effects of short-term lamotrigine treatment on pharmacokinetics of carbamazepine. Author(s): Malminiemi K, Keranen T, Kerttula T, Moilanen E, Ylitalo P. Source: Int J Clin Pharmacol Ther. 2000 November; 38(11): 540-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097146

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Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects. Author(s): Odishaw J, Chen C. Source: Pharmacotherapy. 2000 December; 20(12): 1448-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130217

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Efficacy and safety of lamotrigine in pediatric patients. Author(s): Messenheimer J. Source: Journal of Child Neurology. 2002 February; 17 Suppl 2: 2S34-2S42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952035

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Efficacy of lamotrigine (LTG) monotherapy. Author(s): Panayiotopoulos CP. Source: Epilepsia. 2000 March; 41(3): 357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10714412

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Efficacy of lamotrigine add-on therapy in severe partial epilepsy in adults with drop seizures and secondary bilateral synchrony on EEG. Author(s): Bisulli F, Baruzzi A, Rosati A, Riva R, Avoni P, Cerullo A, Tinuper P. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2001 September; 3(3): 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11679308

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Efficacy of lamotrigine and vigabatrin in drug-resistant epilepsies of childhood. Author(s): Dimova PS, Korinthenberg R. Source: Pediatric Neurology. 1999 November; 21(5): 802-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10593670

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Efficacy of lamotrigine in idiopathic generalized epilepsy syndromes: a video-EEGcontrolled, open study. Author(s): Gericke CA, Picard F, de Saint-Martin A, Strumia S, Marescaux C, Hirsch E. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 1999 September; 1(3): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10937148

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Efficacy of lamotrigine in institutionalized, developmentally disabled patients with epilepsy: a retrospective evaluation. Author(s): Gidal BE, Walker JK, Lott RS, Shaw R, Speth J, Marty KJ, Rutecki P. Source: Seizure : the Journal of the British Epilepsy Association. 2000 March; 9(2): 131-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10845738

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Efficacy of lamotrigine in refractory neonatal seizures. Author(s): Barr PA, Buettiker VE, Antony JH. Source: Pediatric Neurology. 1999 February; 20(2): 161-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10082350

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Efficacy of lamotrigine on sensory symptoms and pain in peripheral neuropathies. Author(s): Carrieri PB, Bonuso S, Bruno R, Vincitorio CM, Caruso G. Source: Journal of Pain and Symptom Management. 1999 September; 18(3): 154-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10517035

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Efficacy, tolerability, and kinetics of lamotrigine in infants. Author(s): Mikati MA, Fayad M, Koleilat M, Mounla N, Hussein R, Kazma A, Yunis K. Source: The Journal of Pediatrics. 2002 July; 141(1): 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091848

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Elevated clozapine plasma level with lamotrigine. Author(s): Kossen M, Selten JP, Kahn RS. Source: The American Journal of Psychiatry. 2001 November; 158(11): 1930. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11691709

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Epilepsy and pregnancy: lamotrigine as main drug used. Author(s): Sabers A, Dam M, A-Rogvi-Hansen B, Boas J, Sidenius P, Laue Friis M, Alving J, Dahl M, Ankerhus J, Mouritzen Dam A. Source: Acta Neurologica Scandinavica. 2004 January; 109(1): 9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653845

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Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Author(s): Posner EB, Mohamed K, Marson AG. Source: Cochrane Database Syst Rev. 2003; (3): Cd003032. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917940

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Exacerbation of juvenile myoclonic epilepsy with lamotrigine. Author(s): Carrazana EJ, Wheeler SD. Source: Neurology. 2001 May 22; 56(10): 1424-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11376212

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Exacerbation of juvenile myoclonic epilepsy with lamotrigine. Author(s): Biraben A, Allain H, Scarabin JM, Schuck S, Edan G. Source: Neurology. 2000 December 12; 55(11): 1758. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11113246

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Extensive fixed drug eruption due to lamotrigine. Author(s): Hsiao CJ, Lee JY, Wong TW, Sheu HM. Source: The British Journal of Dermatology. 2001 June; 144(6): 1289-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422075

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Factors influencing the incidence of lamotrigine-related skin rash. Author(s): Wong IC, Mawer GE, Sander JW. Source: The Annals of Pharmacotherapy. 1999 October; 33(10): 1037-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534214

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Fatal course of toxic epidermal necrolysis under treatment with lamotrigine. Author(s): Sterker M, Berrouschot J, Schneider D. Source: Int J Clin Pharmacol Ther. 1995 November; 33(11): 595-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8688983

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Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review. Author(s): Overstreet K, Costanza C, Behling C, Hassanin T, Masliah E. Source: Digestive Diseases and Sciences. 2002 September; 47(9): 1921-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353830

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Fatal toxic epidermal necrolysis related to lamotrigine administration. Author(s): Page RL 2nd, O'Neil MG, Yarbrough DR 3rd, Conradi S. Source: Pharmacotherapy. 1998 March-April; 18(2): 392-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9545161

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Female genital disorder as adverse symptom of lamotrigine treatment. A serotoninergic effect? Author(s): Erfurth A, Amann B, Grunze H. Source: Neuropsychobiology. 1998 October; 38(3): 200-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9778610

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Fulminant hepatic failure induced by lamotrigine. Author(s): Makin AJ, Fitt S, Williams R, Duncan JS. Source: Bmj (Clinical Research Ed.). 1995 July 29; 311(7000): 292. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7633236

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Gabapentin and lamotrigine in bipolar disorder. Author(s): Botts SR, Raskind J. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 October 1; 56(19): 1939-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10554911

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Gabapentin and lamotrigine in Indian patients of partial epilepsy refractory to carbamazepine. Author(s): Sethi A, Chandra D, Puri V, Mallika V. Source: Neurology India. 2002 September; 50(3): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12391470

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Gabapentin and lamotrigine in the treatment of bipolar disorder. Author(s): Dopheide JA, Wincor MZ. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 1998 September-October; 38(5): 632-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9782699

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Gabapentin and lamotrigine: novel antiepileptic drugs. Author(s): Btaiche IF, Woster PS. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 January 1; 52(1): 61-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879525

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Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy. Author(s): Brodie MJ, Chadwick DW, Anhut H, Otte A, Messmer SL, Maton S, Sauermann W, Murray G, Garofalo EA; Gabapentin Study Group 945-212. Source: Epilepsia. 2002 September; 43(9): 993-1000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12199724

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Guidelines for treating epilepsy in the age of felbamate, vigabatrin, lamotrigine, and gabapentin. Author(s): Laxer KD. Source: The Western Journal of Medicine. 1994 September; 161(3): 309-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7975572

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Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy. Author(s): Morrell MJ, Isojarvi J, Taylor AE, Dam M, Ayala R, Gomez G, O'Neill F, Tennis P, Messenheimer J. Source: Epilepsy Research. 2003 May; 54(2-3): 189-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837570

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High-performance liquid chromatography quantitation of plasma lamotrigine concentrations: application measuring trough concentrations in patients with epilepsy. Author(s): Sallustio BC, Morris RG. Source: Therapeutic Drug Monitoring. 1997 December; 19(6): 688-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9421112

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Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy. Author(s): Stephen LJ, Kwan P, Shapiro D, Dominiczak M, Brodie MJ. Source: Epilepsia. 2001 August; 42(8): 1002-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554885

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Human safety of lamotrigine. Author(s): Betts T, Goodwin G, Withers RM, Yuen AW. Source: Epilepsia. 1991; 32 Suppl 2: S17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1837776

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Hypersensitivity reaction in a child due to lamotrigine. Author(s): Brown TS, Appel JE, Kasteler JS, Callen JP. Source: Pediatric Dermatology. 1999 January-February; 16(1): 46-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10028000

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Hypomania induced by adjunctive lamotrigine. Author(s): Margolese HC, Beauclair L, Szkrumelak N, Chouinard G. Source: The American Journal of Psychiatry. 2003 January; 160(1): 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505823

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Hyponatraemia associated with lamotrigine in cranial diabetes insipidus. Author(s): Mewasingh L, Aylett S, Kirkham F, Stanhope R. Source: Lancet. 2000 August 19; 356(9230): 656. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968444

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Identification and assay of lamotrigine in human milk with gas chromatography and densitometry. Author(s): Wyszomirska E, Czerwinska K. Source: Acta Pol Pharm. 1999 March-April; 56(2): 101-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10635355

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Immunofluorometric assay for lamotrigine (Lamictal) in human plasma. Author(s): Sailstad JM, Findlay JW. Source: Therapeutic Drug Monitoring. 1991 September; 13(5): 433-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1957337

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Impact of lamotrigine on patients with refractory epilepsy: the Leicester experience. Author(s): Martin PJ, Millac PA. Source: Seizure : the Journal of the British Epilepsy Association. 1994 September; 3(3): 209-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8000715

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Improved sexual function in three men taking lamotrigine for epilepsy. Author(s): Husain AM, Carwile ST, Miller PP, Radtke RA. Source: Southern Medical Journal. 2000 March; 93(3): 335-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728528

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In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. Author(s): Magdalou J, Herber R, Bidault R, Siest G. Source: The Journal of Pharmacology and Experimental Therapeutics. 1992 March; 260(3): 1166-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1545383

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Incompleteness of lamotrigine data. Author(s): Acharya NV, Wilton LV, Shakir SA. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2001; 24(2): 155-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11235819

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Influence of cirrhosis on lamotrigine pharmacokinetics. Author(s): Marcellin P, de Bony F, Garret C, Altman C, Boige V, Castelnau C, LaurentPuig P, Trinchet JC, Rolan P, Chen C, Mamet JP, Bidault R. Source: British Journal of Clinical Pharmacology. 2001 May; 51(5): 410-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11421997

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Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children. Author(s): Vauzelle-Kervroedan F, Rey E, Cieuta C, Pariente-Khayat A, Pons G, d'Athis P, Bidault R, Dulac O, Olive G. Source: British Journal of Clinical Pharmacology. 1996 April; 41(4): 325-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8730979

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Influence of lamotrigine addition on computerized background EEG parameters in severe epileptogenic encephalopathies. Author(s): Foletti G, Volanschi D. Source: European Neurology. 1994; 34 Suppl 1: 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8001618

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Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial. Author(s): Kremer B, Clark CM, Almqvist EW, Raymond LA, Graf P, Jacova C, Mezei M, Hardy MA, Snow B, Martin W, Hayden MR. Source: Neurology. 1999 September 22; 53(5): 1000-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10496259

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Influence of lamotrigine over the SUNCT syndrome: one patient follow-up for two years. Author(s): Piovesan EJ, Siow C, Kowacs PA, Werneck LC. Source: Arquivos De Neuro-Psiquiatria. 2003 September; 61(3A): 691-4. Epub 2003 September 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513183

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Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Author(s): May TW, Rambeck B, Jurgens U. Source: Therapeutic Drug Monitoring. 1999 April; 21(2): 175-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10217337

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Interaction of lamotrigine with sodium valproate. Author(s): Pisani F, Di Perri R, Perucca E, Richens A. Source: Lancet. 1993 May 8; 341(8854): 1224. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8098122

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Interaction of lamotrigine with sodium valproate. Author(s): Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO. Source: Lancet. 1993 February 13; 341(8842): 445. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8094217

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Intractable epilepsy in children. The efficacy of lamotrigine treatment, including nonseizure-related benefits. Author(s): Uvebrant P, Bauziene R. Source: Neuropediatrics. 1994 December; 25(6): 284-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7770124

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Is 200mg lamotrigine daily analgesic or not? Author(s): Devulder J. Source: Pain. 2000 May; 86(1-2): 211-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10885968

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Is lamotrigine effective for treatment-refractory mania? Author(s): Koek RJ, Yerevanian BI. Source: Pharmacopsychiatry. 1998 January; 31(1): 35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9524984

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Is there a lamotrigine withdrawal syndrome? Author(s): Gelisse P, Kissani N, Crespel A, Jafari H, Baldy-Moulinier M. Source: Acta Neurologica Scandinavica. 2002 March; 105(3): 232-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886370

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Isolation and characterization of a novel quaternary ammonium-linked glucuronide of lamotrigine. Author(s): Sinz MW, Remmel RP. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1991 January-February; 19(1): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1673389

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Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. Author(s): Depot M, Powell JR, Messenheimer JA Jr, Cloutier G, Dalton MJ. Source: Clinical Pharmacology and Therapeutics. 1990 October; 48(4): 346-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2225696

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Lamotrigine add-on for drug-resistant partial epilepsy. Author(s): Ramaratnam S, Marson AG, Baker GA. Source: Cochrane Database Syst Rev. 2001; (3): Cd001909. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687001

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Lamotrigine and borderline personality disorder. Author(s): Rizvi ST. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Winter; 12(4): 365-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12625999

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Lamotrigine and informed consent. Author(s): Masters KJ, Melonas JM. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2004 February; 43(2): 130-1; Author Reply 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726716

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Lamotrigine and rash: scratching beneath the surface. Author(s): Labiner DM. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 1010-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469685

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Lamotrigine and valproate: efficacy of co-administration in a pediatric population. Author(s): Thome-Souza S, Freitas A, Fiore LA, Valente KD. Source: Pediatric Neurology. 2003 May; 28(5): 360-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878297

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Lamotrigine as adjunctive therapy in patients with refractory epilepsy and mental retardation. Author(s): McKee JR, Sunder TR, FineSmith R, Vuong A, Varner JA, Hammer AE, Barrett PS. Source: Epilepsy & Behavior : E&B. 2003 August; 4(4): 386-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899858

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Lamotrigine as an add-on therapy in intractable paediatric epilepsy--the Kuala Lumpur Hospital experience. Author(s): Vigneswari G, Sofiah A, Hussain IH. Source: Med J Malaysia. 2001 September; 56(3): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11732083

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Lamotrigine augmentation in unipolar depression. Author(s): Rocha FL, Hara C. Source: International Clinical Psychopharmacology. 2003 March; 18(2): 97-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598821

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Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial. Author(s): Simpson DM, McArthur JC, Olney R, Clifford D, So Y, Ross D, Baird BJ, Barrett P, Hammer AE; Lamotrigine HIV Neuropathy Study Team. Source: Neurology. 2003 May 13; 60(9): 1508-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743240

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Lamotrigine for intractable sciatica: correlation between dose, plasma concentration and analgesia. Author(s): Eisenberg E, Damunni G, Hoffer E, Baum Y, Krivoy N. Source: European Journal of Pain (London, England). 2003; 7(6): 485-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575661

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Lamotrigine in adolescent mood disorders. Author(s): Carandang CG, Maxwell DJ, Robbins DR, Oesterheld JR. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 July; 42(7): 750-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819432

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Lamotrigine in mood disorders. Author(s): Green B. Source: Current Medical Research and Opinion. 2003; 19(4): 272-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841919

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Lamotrigine in patients with bipolar disorder and cocaine dependence. Author(s): Brown ES, Nejtek VA, Perantie DC, Orsulak PJ, Bobadilla L. Source: The Journal of Clinical Psychiatry. 2003 February; 64(2): 197-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633129

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Lamotrigine in spinal cord injury pain: a randomized controlled trial. Author(s): Finnerup NB, Sindrup SH, Bach FW, Johannesen IL, Jensen TS. Source: Pain. 2002 April; 96(3): 375-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973012

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Lamotrigine in the treatment of bipolar disorder. Author(s): Bowden CL. Source: Expert Opinion on Pharmacotherapy. 2002 October; 3(10): 1513-9. Review. Erratum In: Expert Opin Pharmacother. 2002 November; 3(11): 1683. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387697

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Lamotrigine in the treatment of depersonalization disorder. Author(s): Sierra M, Phillips ML, Lambert MV, Senior C, David AS, Krystal JH. Source: The Journal of Clinical Psychiatry. 2001 October; 62(10): 826-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816874

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Lamotrigine in the treatment of SUNCT syndrome. Author(s): D'Andrea G, Granella F, Ghiotto N, Nappi G. Source: Neurology. 2001 November 13; 57(9): 1723-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11706123

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Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Author(s): Tiihonen J, Hallikainen T, Ryynanen OP, Repo-Tiihonen E, Kotilainen I, Eronen M, Toivonen P, Wahlbeck K, Putkonen A. Source: Biological Psychiatry. 2003 December 1; 54(11): 1241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14643092

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Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy. Author(s): Kaminow L, Schimschock JR, Hammer AE, Vuong A. Source: Epilepsy & Behavior : E&B. 2003 December; 4(6): 659-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698699

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Lamotrigine monotherapy for control of neuralgia after nerve section. Author(s): Sandner-Kiesling A, Rumpold Seitlinger G, Dorn C, Koch H, Schwarz G. Source: Acta Anaesthesiologica Scandinavica. 2002 November; 46(10): 1261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12421199

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Lamotrigine plasma levels reduced by oral contraceptives. Author(s): Sabers A, Buchholt JM, Uldall P, Hansen EL. Source: Epilepsy Research. 2001 November; 47(1-2): 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673029

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Lamotrigine treatment for post-stroke pathological laughing and crying. Author(s): Ramasubbu R. Source: Clinical Neuropharmacology. 2003 September-October; 26(5): 233-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520162

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Lamotrigine use in geriatric patients with bipolar depression. Author(s): Robillard M, Conn DK. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 October; 47(8): 767-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12420655

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Lamotrigine versus valproate monotherapy-associated weight change in adolescents with epilepsy: results from a post hoc analysis of a randomized, double-blind clinical trial. Author(s): Biton V, Levisohn P, Hoyler S, Vuong A, Hammer AE. Source: Journal of Child Neurology. 2003 February; 18(2): 133-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693782

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Lamotrigine--clozapine combination in refractory schizophrenia: three cases. Author(s): Saba G, Dumortier G, Kalalou K, Benadhira R, Degrassat K, Glikman J, Januel D. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Winter; 14(1): 86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11884664

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Lamotrigine-related skin rashes in adults. Author(s): Huang CW, Tsai JJ, Lai ML. Source: Kaohsiung J Med Sci. 2002 November; 18(11): 566-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12513019

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Latest maintenance data on lamotrigine in bipolar disorder. Author(s): Calabrese JR, Vieta E, Shelton MD. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 August; 13 Suppl 2: S57-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957721

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Long-term monotherapy with lamotrigine in newly diagnosed epilepsy in adults. Author(s): Chmielewska B, Kaminski ML, Kawka Z. Source: Ann Univ Mariae Curie Sklodowska [med]. 2001; 56: 43-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11977353

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Long-term tolerability of lamotrigine: data from a 6-year continuation study. Author(s): Faught E, Matsuo FU, Schachter S, Messenheimer J, Womble GP. Source: Epilepsy & Behavior : E&B. 2004 February; 5(1): 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751204

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Long-term treatment of bipolar disorder with lamotrigine. Author(s): Calabrese JR, Shelton MD, Rapport DJ, Kimmel SE, Elhaj O. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 10: 18-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392349

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Maintenance ECT replaced with lamotrigine. Author(s): Rhodes LJ. Source: The American Journal of Psychiatry. 2000 December; 157(12): 2058. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097987

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Measurement of lamotrigine under conditions measuring phenobarbitone, phenytoin, and carbamazepine using reversed-phase high-performance liquid chromatography at dual wavelengths. Author(s): Ramachandran S, Underhill S, Jones SR. Source: Therapeutic Drug Monitoring. 1994 February; 16(1): 75-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8160260

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Methsuximide lowers lamotrigine blood levels: A pharmacokinetic antiepileptic drug interaction. Author(s): Besag FM, Berry DJ, Pool F. Source: Epilepsia. 2000 May; 41(5): 624-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10802770

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Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Author(s): Kuzniecky R, Ho S, Pan J, Martin R, Gilliam F, Faught E, Hetherington H. Source: Neurology. 2002 February 12; 58(3): 368-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11839834

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Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by the glutamate release-inhibiting drug lamotrigine. Author(s): Makatsori A, Duncko R, Moncek F, Loder I, Katina S, Jezova D. Source: Neuroendocrinology. 2004 January; 79(1): 34-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755132

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Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group. Author(s): Brodie MJ, Overstall PW, Giorgi L. Source: Epilepsy Research. 1999 October; 37(1): 81-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10515178

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Multiorgan dysfunction and disseminated intravascular coagulation in children receiving lamotrigine and valproic acid. Author(s): Chattergoon DS, McGuigan MA, Koren G, Hwang P, Ito S. Source: Neurology. 1997 November; 49(5): 1442-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9371937

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Multisystem adverse reaction to lamotrigine. Author(s): Schaub JE, Williamson PJ, Barnes EW, Trewby PN. Source: Lancet. 1994 August 13; 344(8920): 481. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7914595

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Multisystem hypersensitivity reaction to lamotrigine. Author(s): Sarris BM, Wong JG. Source: Neurology. 1999 October 12; 53(6): 1367. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10522908

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Myoclonic status epilepticus following high-dosage lamotrigine therapy. Author(s): Guerrini R, Belmonte A, Parmeggiani L, Perucca E. Source: Brain & Development. 1999 September; 21(6): 420-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487478

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Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Author(s): Wallace SJ. Source: Epilepsy Research. 1998 January; 29(2): 147-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9477147

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Neuralgic amyotrophy associated with hypersensitivity to lamotrigine. Author(s): Hennessy MJ, Koutroumanidis M, Elwes RD. Source: Neurology. 1998 October; 51(4): 1224. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781570

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Neurophysiologic and neuropsychologic profiles of lamotrigine in epilepsy. Author(s): Marciani MG, Spanedda F, Mattia D. Source: Clinical Neuropharmacology. 1999 May-June; 22(3): 159-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367180

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Neurophysiological evaluation of vigilance in epileptic patients on monotherapy with lamotrigine. Author(s): Bonanni E, Galli R, Gori S, Pasquali L, Maestri M, Iudice A, Murri L. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 June; 112(6): 1018-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377260

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Neuropsychological assessment in lamotrigine treated epileptic patients. Author(s): Banks GK, Beran RG. Source: Clin Exp Neurol. 1991; 28: 230-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1821833

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New antiepileptic drugs for children: felbamate, gabapentin, lamotrigine, and vigabatrin. Author(s): Devinsky O, Vazquez B, Luciano D. Source: Journal of Child Neurology. 1994 October; 9 Suppl 1: S33-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7822751

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New concepts in mood stabilization: evidence for the effectiveness of valproate and lamotrigine. Author(s): Bowden CL. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1998 September; 19(3): 194-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9653707

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New high-performance liquid chromatographic method for plasma/serum analysis of lamotrigine. Author(s): Croci D, Salmaggi A, de Grazia U, Bernardi G. Source: Therapeutic Drug Monitoring. 2001 December; 23(6): 665-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11802101

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New micromethod for the determination of lamotrigine in human plasma by highperformance liquid chromatography. Author(s): Londero D, Lo Greco P. Source: J Chromatogr B Biomed Sci Appl. 1997 March 28; 691(1): 139-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9140767

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Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin. Author(s): Curry WJ, Kulling DL. Source: American Family Physician. 1998 February 1; 57(3): 513-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9475899

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No increase in carbamazepine-10,11-epoxide during addition of lamotrigine treatment in children. Author(s): Eriksson AS, Boreus LO. Source: Therapeutic Drug Monitoring. 1997 October; 19(5): 499-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9357090

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Non convulsive status epilepticus after replacement of valproate with lamotrigine. Author(s): Trinka E, Dilitz E, Unterberger I, Luef G, Deisenhammer F, Niedermuller U, Thaler C, Bauer G. Source: Journal of Neurology. 2002 October; 249(10): 1417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382160

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Normal growth during lamotrigine monotherapy in pediatric epilepsy patients -- a prospective evaluation of 103 children and adolescents. Author(s): Ueberall MA. Source: Epilepsy Research. 2001 July; 46(1): 63-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11395290

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Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy. Author(s): Jozwiak S, Terczynski A. Source: Seizure : the Journal of the British Epilepsy Association. 2000 October; 9(7): 48692. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034873

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Open trial lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation. Author(s): Davanzo PA, King BH. Source: Journal of Child and Adolescent Psychopharmacology. 1996 Winter; 6(4): 273-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9231320

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Optimized high-performance liquid chromatographic method for determination of lamotrigine in serum with concomitant determination of phenytoin, carbamazepine, and carbamazepine epoxide. Author(s): Lensmeyer GL, Gidal BE, Wiebe DA. Source: Therapeutic Drug Monitoring. 1997 June; 19(3): 292-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9200770

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Optimized procedure for lamotrigine analysis in serum by high-performance liquid chromatography without interferences from other frequently coadministered anticonvulsants. Author(s): Torra M, Rodamilans M, Arroyo S, Corbella J. Source: Therapeutic Drug Monitoring. 2000 October; 22(5): 621-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034270

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Oral contraceptives reduce lamotrigine plasma levels. Author(s): Sabers A, Ohman I, Christensen J, Tomson T. Source: Neurology. 2003 August 26; 61(4): 570-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12939444

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Outcomes of add-on treatment with lamotrigine in partial epilepsy. Author(s): Smith D, Baker G, Davies G, Dewey M, Chadwick DW. Source: Epilepsia. 1993 March-April; 34(2): 312-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8453943

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Overdose with gabapentin and lamotrigine. Author(s): Stopforth J. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1997 October; 87(10): 1388. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9472258

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Overview of lamotrigine and the new antiepileptic drugs: the challenge. Author(s): Pellock JM. Source: Journal of Child Neurology. 1997 November; 12 Suppl 1: S48-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9429131

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Overview of the clinical efficacy of lamotrigine. Author(s): Richens A, Yuen AW. Source: Epilepsia. 1991; 32 Suppl 2: S13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1837775

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Palatal myoclonus responding to lamotrigine. Author(s): Nasr A, Brown N. Source: Seizure : the Journal of the British Epilepsy Association. 2002 March; 11(2): 1367. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11945102

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Paradoxic reaction to lamotrigine in a child with benign focal epilepsy of childhood with centrotemporal spikes. Author(s): Catania S, Cross H, de Sousa C, Boyd S. Source: Epilepsia. 1999 November; 40(11): 1657-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565596

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Peri-marketing surveillance of lamotrigine in The Netherlands: doctors' and patients' viewpoints. Author(s): Trenite DG, Rentmeester TW, Scholtes FB, Gilissen KG, Arends LR, Schlosser A. Source: Pharmacy World & Science : Pws. 2001 February; 23(1): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344584

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Persistent migrainous visual phenomena might be responsive to lamotrigine. Author(s): Chen WT, Fuh JL, Lu SR, Wang SJ. Source: Headache. 2001 September; 41(8): 823-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576209

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Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Author(s): Hermann R, Knebel NG, Niebch G, Richards L, Borlak J, Locher M. Source: European Journal of Clinical Pharmacology. 2003 April; 58(12): 795-802. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698305

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Phenotypic spectra of bipolar disorder in responders to lithium versus lamotrigine. Author(s): Passmore MJ, Garnham J, Duffy A, MacDougall M, Munro A, Slaney C, Teehan A, Alda M. Source: Bipolar Disorders. 2003 April; 5(2): 110-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680900

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Phenytoin-like hypersensitivity associated with lamotrigine. Author(s): Tugendhaft P, Simonart T. Source: Journal of the American Academy of Dermatology. 1998 May; 38(5 Pt 1): 785. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591836

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Phenytoin-like hypersensitivity associated with lamotrigine. Author(s): Jones D, Chhiap V, Resor S, Appel G, Grossman ME. Source: Journal of the American Academy of Dermatology. 1997 June; 36(6 Pt 1): 1016-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9204073

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Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data. Author(s): Hussein Z, Posner J. Source: British Journal of Clinical Pharmacology. 1997 May; 43(5): 457-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9159559

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Population pharmacokinetics of lamotrigine. Author(s): Chan V, Morris RG, Ilett KF, Tett SE. Source: Therapeutic Drug Monitoring. 2001 December; 23(6): 630-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11802095

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Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Author(s): Ettinger AB, Weisbrot DM, Saracco J, Dhoon A, Kanner A, Devinsky O. Source: Epilepsia. 1998 August; 39(8): 874-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9701379

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Positive patch test in hypersensitivity to lamotrigine. Author(s): Monzon S, Garces MM, Reichelt C, Lezaun A, Colas C. Source: Contact Dermatitis. 2002 December; 47(6): 361. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581284

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Possible usefulness of lamotrigine in the treatment of SUNCT syndrome. Author(s): D'Andrea G, Granella F, Cadaldini M. Source: Neurology. 1999 October 22; 53(7): 1609. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534285

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Postmortem investigation of lamotrigine concentrations. Author(s): Pricone MG, King CV, Drummer OH, Opeskin K, McIntyre IM. Source: J Forensic Sci. 2000 January; 45(1): 11-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10641913

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Potential hepatotoxicity of lamotrigine. Author(s): Fayad M, Choueiri R, Mikati M. Source: Pediatric Neurology. 2000 January; 22(1): 49-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10669206

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Potential mechanisms of action of lamotrigine in the treatment of bipolar disorders. Author(s): Ketter TA, Manji HK, Post RM. Source: Journal of Clinical Psychopharmacology. 2003 October; 23(5): 484-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520126

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Prolonged anticonvulsant hypersensitivity syndrome related to lamotrigine in a patient with human immunodeficiency virus. Author(s): Beller TC, Boyce JA. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2002 November-December; 23(6): 415-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528608

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Prolonged toxic epidermal necrolysis due to Lamotrigine. Author(s): Bhushan M, Brooke R, Hewitt-Symonds M, Craven NM, August PJ. Source: Clinical and Experimental Dermatology. 2000 June; 25(4): 349-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971500

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Prospective study on concentration-efficacy and concentration-toxicity: correlations with lamotrigine serum levels. Author(s): Froscher W, Keller F, Vogt H, Kramer G. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2002 March; 4(1): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967180

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Prospective, open-label, add-on study of lamotrigine in 56 children with intractable generalized epilepsy. Author(s): Farrell K, Connolly MB, Munn R, Peng S, MacWilliam LM. Source: Pediatric Neurology. 1997 April; 16(3): 201-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9165509

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Psychotic disorder after lamotrigine. Author(s): Polselli GM, Pennisi EM, Figa Talamanca L, Roberti R, Garelli FF, Bandinelli PL. Source: Italian Journal of Neurological Sciences. 1998 April; 19(2): 124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10935851

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Randomized double-blind parallel-group study comparing cognitive effects of a lowdose lamotrigine with valproate and placebo in healthy volunteers. Author(s): Aldenkamp AP, Arends J, Bootsma HP, Diepman L, Hulsman J, Lambrechts D, Leenen L, Majoie M, Schellekens A, de Vocht J. Source: Epilepsia. 2002 January; 43(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879382

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Rash in adult and pediatric patients treated with lamotrigine. Author(s): Messenheimer JA. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1998 November; 25(4): S14-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9827240

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Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. Author(s): Calabrese JR, Sullivan JR, Bowden CL, Suppes T, Goldberg JF, Sachs GS, Shelton MD, Goodwin FK, Frye MA, Kusumakar V. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 1012-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444815

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Rash with lamotrigine: dosing guidelines. Author(s): Messenheimer JA, Guberman AH. Source: Epilepsia. 2000 April; 41(4): 488. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10756418

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Re: Sadler's article regarding lamotrigine-associated insomnia in an adult tertiary care epilepsy out-patient clinic. Author(s): Cochrane Database Syst Rev. 2001;(3):CD001909 Source: Epilepsia. 2000 July; 41(7): 920-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687001

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Rechallenge with lamotrigine after initial rash. Author(s): Tavernor SJ, Wong IC, Newton R, Brown SW. Source: Seizure : the Journal of the British Epilepsy Association. 1995 March; 4(1): 67-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7788112

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Rectal absorption of lamotrigine compressed tablets. Author(s): Birnbaum AK, Kriel RL, Burkhardt RT, Remmel RP. Source: Epilepsia. 2000 July; 41(7): 850-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10897156

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Recurrence of lamotrigine-associated rash with rechallenge. Author(s): Buzan RD, Dubovsky SL. Source: The Journal of Clinical Psychiatry. 1998 February; 59(2): 87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9501897

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Relative bioavailability of lamotrigine chewable dispersible tablets administered rectally. Author(s): Birnbaum AK, Kriel RL, Im Y, Remmel RP. Source: Pharmacotherapy. 2001 February; 21(2): 158-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213851

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Reversible aphasic disorder induced by lamotrigine in atypical benign childhood epilepsy. Author(s): Battaglia D, Iuvone L, Stefanini MC, Acquafondata C, Lettori D, Chiricozzi F, Pane M, Mittica A, Guzzetta F. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2001 December; 3(4): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844717

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Review of lamotrigine and its clinical applications in epilepsy. Author(s): Choi H, Morrell MJ. Source: Expert Opinion on Pharmacotherapy. 2003 February; 4(2): 243-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562315

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Role of vigabatrin and lamotrigine in treatment of childhood epileptic syndromes. Author(s): Belanger S, Coulombe G, Carmant L. Source: Epilepsia. 1998 August; 39(8): 878-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9701380

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Routine therapeutic monitoring of lamotrigine in epileptic patients using a simple and rapid high performance liquid chromatographic technique. Author(s): George S, Wood AJ, Braithwaite RA. Source: Annals of Clinical Biochemistry. 1995 November; 32 ( Pt 6): 584-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8579292

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Routine use of lamotrigine, a new anti-epileptic medication, and the value of measuring its blood levels. Author(s): Beran RG, Sheehan K, Tilley MI. Source: Clin Exp Neurol. 1994; 31: 61-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7586666

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Safety of long-term lamotrigine in epilepsy. Author(s): Mackay FJ, Wilton LV, Pearce GL, Freemantle SN, Mann RD. Source: Epilepsia. 1997 August; 38(8): 881-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579888

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Safety review of adult clinical trial experience with lamotrigine. Author(s): Messenheimer J, Mullens EL, Giorgi L, Young F. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1998 April; 18(4): 281-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565739

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Saliva and serum concentration of lamotrigine in patients with epilepsy. Author(s): Tsiropoulos I, Kristensen O, Klitgaard NA. Source: Therapeutic Drug Monitoring. 2000 October; 22(5): 517-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034255

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Simple and rapid analysis of lamotrigine, a novel antiepileptic, in human serum by high-performance liquid chromatography using a solid-phase extraction technique. Author(s): Yamashita S, Furuno K, Kawasaki H, Gomita Y, Yoshinaga H, Yamatogi Y, Ohtahara S. Source: Journal of Chromatography. B, Biomedical Applications. 1995 August 18; 670(2): 354-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8548028

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Single-dose pharmacokinetics of lamotrigine in children: influence of age and antiepileptic comedication. Author(s): Battino D, Croci D, Granata T, Mamoli D, Messina S, Perucca E. Source: Therapeutic Drug Monitoring. 2001 June; 23(3): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11360028

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Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Author(s): Calabrese JR, Bowden CL, McElroy SL, Cookson J, Andersen J, Keck PE Jr, Rhodes L, Bolden-Watson C, Zhou J, Ascher JA. Source: The American Journal of Psychiatry. 1999 July; 156(7): 1019-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401445

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Spotlight on lamotrigine in bipolar disorder. Author(s): Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Source: Cns Drugs. 2004; 18(1): 63-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14731061

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Stability of lamotrigine in two extemporaneously prepared oral suspensions at 4 and 25 degrees C. Author(s): Nahata MC, Morosco RS, Hipple TF. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 February 1; 56(3): 240-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10030509

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Stable weight during lamotrigine therapy: a review of 32 studies. Author(s): Devinsky O, Vuong A, Hammer A, Barrett PS. Source: Neurology. 2000 February 22; 54(4): 973-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10690996

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Stevens-Johnson syndrome associated with concomitant use of lamotrigine and valproic acid. Author(s): Yalcin B, Karaduman A. Source: Journal of the American Academy of Dermatology. 2000 November; 43(5 Pt 2): 898-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044815

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Stimulating consciousness and cognition following severe brain injury: a new potential clinical use for lamotrigine. Author(s): Showalter PE, Kimmel DN. Source: Brain Injury : [bi]. 2000 November; 14(11): 997-1001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104139

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Stupor from lamotrigine toxicity. Author(s): Sbei M, Campellone JV. Source: Epilepsia. 2001 August; 42(8): 1082-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554897

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Successful antimanic treatment and mood stabilization with lamotrigine, clozapine, and valproate in a bipolar patient after lithium-induced cerebellar deterioration. A case report. Author(s): Dembowski C, Rechlin T. Source: Pharmacopsychiatry. 2003 March-April; 36(2): 83-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734768

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Successful re-introduction of lamotrigine after initial rash. Author(s): Besag FM, Ng GY, Pool F. Source: Seizure : the Journal of the British Epilepsy Association. 2000 June; 9(4): 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10880290

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Successful treatment of lamotrigine-induced erythroblastopenic crisis with folinic acid. Author(s): Pulik M, Lionnet F, Genet P. Source: Neurology. 2000 October 24; 55(8): 1235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11071512

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SUNCT syndrome responsive to lamotrigine. Author(s): Gutierrez-Garcia JM. Source: Headache. 2002 September; 42(8): 823-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390648

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SUNCT syndrome responsive to lamotrigine: documentation of the first Indian case. Author(s): Chakravarty A, Mukherjee A. Source: Cephalalgia : an International Journal of Headache. 2003 July; 23(6): 474-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807528

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Suspected allergy to lamotrigine. Author(s): Gucuyener K, Turktas I, Serdaroglu A, Ezgu FS. Source: Allergy. 1999 July; 54(7): 767-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442540

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Suspected lamotrigine-induced toxic epidermal necrolysis. Author(s): Sogut A, Yilmaz A, Kilinc M, Sogut AG, Demiralay E, Uzar H. Source: Acta Neurol Belg. 2003 June; 103(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892003

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Suspected lamotrigine-induced toxic epidermal necrolysis. Author(s): Chaffin JJ, Davis SM. Source: The Annals of Pharmacotherapy. 1997 June; 31(6): 720-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9184711

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The effect of lamotrigine on epileptiform discharges in young patients with drugresistant epilepsy. Author(s): Eriksson AS, Knutsson E, Nergardh A. Source: Epilepsia. 2001 February; 42(2): 230-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240595

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The effect of lamotrigine on naloxone-precipitated opiate withdrawal. Author(s): Rosen MI, Pearsall HR, Kosten TR. Source: Drug and Alcohol Dependence. 1998 October 1; 52(2): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9800147

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The effect of lamotrigine on the EEGs of children and adolescents with epilepsy. Author(s): Akman CI, Holmes GL. Source: Epilepsy & Behavior : E&B. 2003 August; 4(4): 420-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899863

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The effects of lamotrigine on sleep in patients with epilepsy. Author(s): Foldvary N, Perry M, Lee J, Dinner D, Morris HH. Source: Epilepsia. 2001 December; 42(12): 1569-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879368

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The effects of lamotrigine on the pharmacokinetics of lithium. Author(s): Chen C, Veronese L, Yin Y. Source: British Journal of Clinical Pharmacology. 2000 September; 50(3): 193-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971302

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The efficacy of lamotrigine in children and adolescents with refractory generalized epilepsy: a randomized, double-blind, crossover study. Author(s): Eriksson AS, Nergardh A, Hoppu K. Source: Epilepsia. 1998 May; 39(5): 495-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9596201

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The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder. Author(s): Hamer RM, Simpson PM. Source: Biological Psychiatry. 1999 December 15; 46(12): 1711-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10624556

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The incorporation of lamotrigine into the routine automated sequential trace enrichment of dialysates assay of anticonvulsants. Author(s): Higgins G, Hughes A, Dutton J, Roberts NB. Source: Annals of Clinical Biochemistry. 1998 July; 35 ( Pt 4): 534-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9681056

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The long-term use of gabapentin, lamotrigine, and vigabatrin in patients with chronic epilepsy. Author(s): Wong IC, Chadwick DW, Fenwick PB, Mawer GE, Sander JW. Source: Epilepsia. 1999 October; 40(10): 1439-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10528941

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The long-term use of vigabatrin and lamotrigine in patients with severe childhood onset epilepsy. Author(s): Kluger G, Berz K, Holthausen H. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2001; 5(1): 37-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277363

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The name game: lamivudine-lamotrigine dispensing error presenting as human immunodeficiency virus-associated fever of unknown origin. Author(s): Fowler VG Jr, Hicks CB, Kirkland KB. Source: International Journal of Std & Aids. 1999 October; 10(10): 685-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10582639

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The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalised epilepsies. Author(s): Nicolson A, Appleton RE, Chadwick DW, Smith DF. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 January; 75(1): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707312

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The role of lamotrigine in the treatment of epilepsy. Author(s): Leppik IE. Source: Neurology. 1998 October; 51(4): 940-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781508

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The tolerability of lamotrigine in elderly patients with epilepsy. Author(s): Giorgi L, Gomez G, O'Neill F, Hammer AE, Risner M. Source: Drugs & Aging. 2001; 18(8): 621-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11587248

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The use of lamotrigine in neuropathic pain. Author(s): di Vadi PP, Hamann W. Source: Anaesthesia. 1998 August; 53(8): 808-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9797526

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Therapeutic drug monitoring of lamotrigine in patients suffering from resistant partial seizures. Author(s): Benetello P, Furlanut M, Baraldo M, Tonon A, Furlanut M. Source: European Neurology. 2002; 48(4): 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422067

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Therapeutic drug monitoring of lamotrigine using capillary electrophoresis. Evaluation of assay performance and quality assurance over a 4-year period in the routine arena. Author(s): Theurillat R, Kuhn M, Thormann W. Source: J Chromatogr A. 2002 December 6; 979(1-2): 353-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498267

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Tolerability and pharmacokinetics of oral loading with lamotrigine in epilepsy monitoring units. Author(s): Lardizabal DV, Morris HH, Hovinga CA, Del Mar Carreno M. Source: Epilepsia. 2003 April; 44(4): 536-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12681002

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Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients. Author(s): Doose DR, Brodie MJ, Wilson EA, Chadwick D, Oxbury J, Berry DJ, Schwabe S, Bialer M. Source: Epilepsia. 2003 July; 44(7): 917-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823574

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Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo. Author(s): Myllynen PK, Pienimaki PK, Vahakangas KH. Source: European Journal of Clinical Pharmacology. 2003 February; 58(10): 677-82. Epub 2003 January 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12610744

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Unusual side effects of lamotrigine therapy. Author(s): Das KB, Harris C, Smyth DP, Cross JH. Source: Journal of Child Neurology. 2003 July; 18(7): 479-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940653

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Use of lamotrigine in a patient with bipolar disorder and psychiatric comorbidity. Author(s): Ballasiotes AA, Skaer TL. Source: Clinical Therapeutics. 2000 September; 22(9): 1146-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11048910

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Use of lamotrigine in Lennox-Gastaut and related epilepsy syndromes. Author(s): Dulac O, Kaminska A. Source: Journal of Child Neurology. 1997 November; 12 Suppl 1: S23-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9429127

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Use of lamotrigine to treat paroxysmal kinesigenic choreoathetosis. Author(s): Pereira AC, Loo WJ, Bamford M, Wroe SJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 June; 68(6): 796-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10877627

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Use of thermospray liquid chromatography-mass spectrometry to aid in the identification of urinary metabolites of a novel antiepileptic drug, Lamotrigine. Author(s): Doig MV, Clare RA. Source: Journal of Chromatography. 1991 August 21; 554(1-2): 181-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1795036

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Utility of the lethargic (lh/lh) mouse model of absence seizures in predicting the effects of lamotrigine, vigabatrin, tiagabine, gabapentin, and topiramate against human absence seizures. Author(s): Hosford DA, Wang Y. Source: Epilepsia. 1997 April; 38(4): 408-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9118845

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Validated high-performance liquid chromatographic method for the determination of lamotrigine in human plasma. Author(s): Barbosa NR, Midio AF. Source: J Chromatogr B Biomed Sci Appl. 2000 May 12; 741(2): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10872598

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Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children. Author(s): Chen C. Source: British Journal of Clinical Pharmacology. 2000 August; 50(2): 135-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10930965

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Validation of a radioimmunoassay for the determination of human plasma concentrations of lamotrigine. Author(s): Biddlecombe RA, Dean KL, Smith CD, Jeal SC. Source: Journal of Pharmaceutical and Biomedical Analysis. 1990; 8(8-12): 691-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2100608

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Valproate and lamotrigine in migraine. Author(s): Mathew NT. Source: Cephalalgia : an International Journal of Headache. 1997 April; 17(2): 101-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9137845

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Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Author(s): Isojarvi JI, Rattya J, Myllyla VV, Knip M, Koivunen R, Pakarinen AJ, Tekay A, Tapanainen JS. Source: Annals of Neurology. 1998 April; 43(4): 446-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9546324

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Valproic acid and lamotrigine treatment during pregnancy. The risk of chromosomal abnormality. Author(s): Ozkinay F, Cogulu O, Gunduz C, Yilmaz D, Kultursay N. Source: Mutation Research. 2003 January 10; 534(1-2): 197-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504768

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Vigabatrin and lamotrigine in refractory epilepsy. Author(s): Stolarek I, Blacklaw J, Forrest G, Brodie MJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1994 August; 57(8): 921-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8057114

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Visual loss in a patient with lamotrigine-induced cicatrizing conjunctivitis. Author(s): McDonald MA, Favilla I. Source: Clinical & Experimental Ophthalmology. 2003 December; 31(6): 541-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641167

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Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Author(s): Luef G, Abraham I, Trinka E, Unterberger I, Hoppichler F, Bauer G, Lechleitner M. Source: Neurology. 2001 August 14; 57(3): 565-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502944

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Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Author(s): Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS. Source: Neurology. 2001 January 23; 56(2): 172-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11160951

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

Finding Nutrition Studies on Lamotrigine 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 “lamotrigine” (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 “lamotrigine” (or a synonym): •

A cost minimization study comparing vigabatrin, lamotrigine and gabapentin for the treatment of intractable partial epilepsy. Author(s): Department of Economics, City University, London, UK. Source: Hughes, D Cockerell, O C Seizure. 1996 June; 5(2): 89-95 1059-1311

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A naturalistic study of the use of vigabatrin, lamotrigine and gabapentin in adults with learning disabilities. Author(s): Fosse Health Trust, Leicester Frith Hospital, UK. Source: Bhaumik, S Branford, D Duggirala, C Ismail, I A Seizure. 1997 April; 6(2): 127-33 1059-1311

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A survey comparing lamotrigine and vigabatrin in everyday clinical practice. Author(s): Department of Neurological Science, Walton Centre for Neurology & Neurosurgery, Liverpool, U.K. Source: Schapel, G Chadwick, D Seizure. 1996 December; 5(4): 267-70 1059-1311

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A survey of lamotrigine and vigabatrin treatment in children with severe epilepsy. Author(s): Department of Pharmacology and Therapeutics, University of Wales College of Medicine and University Hospital of Wales, Heath Park, Cardiff, UK. Source: Schapel, G J Wallace, S J Gordon, G S Seizure. 1997 December; 6(6): 479-83 10591311

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Addition of lamotrigine to valproate may enhance efficacy in the treatment of bipolar affective disorder. Author(s): University of Freiburg, Department of Psychiatry and Psychotherapy, Germany. Source: Walden, J Hesslinger, B van Calker, D Berger, M Pharmacopsychiatry. 1996 September; 29(5): 193-5 0176-3679

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Allergic skin rash with lamotrigine and concomitant valproate therapy: evidence for an increased risk. Author(s): Chalfont Centre for Epilepsy, National Hospital, United Kingdom. Source: Li, L M Russo, M O'Donoghue, M F Duncan, J S Sander, J W ArqNeuropsiquiatr. 1996 March; 54(1): 47-9 0004-282X

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Anticonvulsant actions of lamotrigine on spontaneous thalamocortical rhythms. Author(s): Department of Anatomy, Medical College of Virginia of Virginia Commonwealth University, Richmond, Virginia, USA. Source: Gibbs, John W 3rd Zhang, Yun Fu Ahmed, Hasan S Coulter, Douglas A Epilepsia. 2002 April; 43(4): 342-9 0013-9580

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Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage? Author(s): Department of Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia. Source: Morris, R G Black, A B Lam, E Westley, I S Ther-Drug-Monit. 2000 December; 22(6): 656-60 0163-4356

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Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception. Author(s): Department of Pharmacology, Epilepsy Research and Education Program, College of Pharmacy, University of Minnesota, 7-170 WDH, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.

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Source: Laughlin, T M Tram, K V Wilcox, G L Birnbaum, A K J-Pharmacol-Exp-Ther. 2002 September; 302(3): 1168-75 0022-3565 •

Effect of gabapentin and lamotrigine on mechanical allodynia-like behaviour in a rat model of trigeminal neuropathic pain. Author(s): Unite de Recherches de Physiopharmacologie du Systeme Nerveux, INSERM U-161, 2 rue d'Alesia, 75014 Paris, France. Source: Christensen, D Gautron, M Guilbaud, G Kayser, V Pain. 2001 August; 93(2): 14753 0304-3959

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Effect of lamotrigine on a novel model of epilepsy. Author(s): Department of Pharmacology, University of Science and Technology, School of Medicine, Irbid, Jordan. Source: Otoom, S A Nusier, M K Cytobios. 2001; 106 Suppl 1: 75-83 0011-4529

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Lack of an effect of topiramate on lamotrigine serum concentrations. Author(s): National Centre for Young People with Epilepsy, St. Piers Lane, Lingfield, Surrey, England. [email protected] Source: Berry, David J Besag, Frank M C Pool, Felicity NataraJanuary, Jaya Doose, Dennis Epilepsia. 2002 August; 43(8): 818-23 0013-9580

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Lamotrigine and the treatment of mania in bipolar disorder. Author(s): Department of Psychiatry, University of the Witwatersrand Medical School, Parktown, South Africa. [email protected] Source: Berk, M Eur-Neuropsychopharmacol. 1999 August; 9 Suppl 4S119-23 0924-977X

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Lamotrigine as an add-on drug in typical absence seizures. Author(s): Department of Paediatric Neurology, Guy's Hospital, London, England. Source: Ferrie, C D Robinson, R O Knott, C Panayiotopoulos, C P Acta-Neurol-Scand. 1995 March; 91(3): 200-2 0001-6314

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Lamotrigine drug interactions in a TDM material. Author(s): Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden. Source: Bottiger, Y Svensson, J O Stahle, L Ther-Drug-Monit. 1999 April; 21(2): 171-4 0163-4356

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Lamotrigine in the treatment of bipolar depression. Author(s): Department of Psychiatry, University of Texas, Health Science Center at San Antonio, 78284-7792, USA. Source: Bowden, C L Mitchell, P Suppes, T Eur-Neuropsychopharmacol. 1999 August; 9 Suppl 4S113-7 0924-977X

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Lamotrigine induced selective changes in 5-HT(1A) receptor mediated response in rat brain. Author(s): Department of Neurochemistry, National Institute of Mental Health and Neurosciences, P.B. No. 2900, Bangalore-560029, India. Source: Vinod, K Y Subhash, M N Neurochem-Int. 2002 April; 40(4): 315-9 0197-0186

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Lamotrigine update and its use in mood disorders. Author(s): College of Pharmacy, Idaho State University, Pocatello, ID, USA. [email protected] Source: Hurley, S C Ann-Pharmacother. 2002 May; 36(5): 860-73 1060-0280

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Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Author(s): Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.

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Source: Guo, C Y Ronen, G M Atkinson, S A Epilepsia. 2001 September; 42(9): 1141-7 0013-9580 •

Neocortical potassium currents are enhanced by the antiepileptic drug lamotrigine. Author(s): Dipartimento di Neuroscienze, Universita degli Studi di Roma Tor Vergata, Roma, Italy. Source: Zona, Cristina Tancredi, Virginia Longone, Patrizia D'Arcangelo, Giovanna D'Antuono, Margherita Manfredi, Mario Avoli, Massimo Epilepsia. 2002 July; 43(7): 68590 0013-9580

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Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy. Author(s): Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Republic of China. Source: Lee, W T Shen, Y Z Chang, C Neuroscience. 2000; 95(1): 89-95 0306-4522

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Peripheral antinociceptive action of morphine and the synergistic interaction with lamotrigine. Author(s): Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Granjas Coapa, Mexico. Source: Arguelles, Carlos F Torres Lopez, Jorge E Granados Soto, Vinicio Anesthesiology. 2002 April; 96(4): 921-5 0003-3022

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Potential use of gabapentin and lamotrigine. Author(s): Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison 53792, USA. Source: Cory, P R Gidal, B e Ann-Pharmacother. 1995 November; 29(11): 1160-1 10600280

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Serum concentrations of lamotrigine in epileptic patients: the influence of dose and comedication. Author(s): Department of Biochemistry, Gesellschaft fur Epilepsieforschung, Bielefeld, Germany. Source: May, T W Rambeck, B Jurgens, U Ther-Drug-Monit. 1996 October; 18(5): 523-31 0163-4356

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Severe hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro. Author(s): Department of Dermatology, University Hospital, Basel, Switzerland. Source: Schaub, N Bircher, A J Allergy. 2000 February; 55(2): 191-3 0105-4538

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Sodium currents in striatal neurons from dystonic dt(sz) hamsters: altered response to lamotrigine. Author(s): Institute of Physiology, Department of Neurophysiology, Westfalische Wilhelms-Universitat Munster, Germany. Source: Siep, E Richter, A Loscher, W Speckmann, E J Kohling, R Neurobiol-Dis. 2002 March; 9(2): 258-68 0969-9961

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The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Author(s): Neurology Clinic, Institute of Neurological and Neurosurgical Sciences, University of Messina, Italy. Source: Pisani, F Oteri, G Russo, M F Di Perri, R Perucca, E Richens, A Epilepsia. 1999 August; 40(8): 1141-6 0013-9580

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The use of lamotrigine in juvenile myoclonic epilepsy. Author(s): Epilepsy Unit, Westmead Hospital, Sydney, Australia. Source: Buchanan, N Seizure. 1996 June; 5(2): 149-51 1059-1311

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Therapeutic interaction of lamotrigine and sodium valproate in intractable myoclonic epilepsy. Author(s): Department of Clinical Neurophysiology and Epilepsy, St Thomas' Hospital London, UK. Source: Ferrie, C D Panayiotopoulos, C P Seizure. 1994 June; 3(2): 157-9 1059-1311

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Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam. Author(s): Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Source: Krupp, E Heynen, T Li, X L Post, R M Weiss, S R Exp-Neurol. 2000 April; 162(2): 278-89 0014-4886

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Valproate, but not lamotrigine, induces ovarian morphological changes in Wistar rats. Author(s): Department of Neurology, Rikshospitalet/The National Hospital, University of Oslo, Norway. Source: Roste, L S Tauboll, E Berner, A Isojarvi, J I Gjerstad, L Exp-Toxicol-Pathol. 2001 February; 52(6): 545-52 0940-2993

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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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

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CHAPTER 3. CLINICAL TRIALS AND LAMOTRIGINE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning lamotrigine.

Recent Trials on Lamotrigine The following is a list of recent trials dedicated to lamotrigine.8 Further information on a trial is available at the Web site indicated. •

CREST-I: Resperine, Gabapentin, or Lamotrigine vs. Placebo - 7 Condition(s): Cocaine-Related Disorders Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: A Modified Placebo-Controlled Study for the Treatment of Cocaine Dependence Using Reserpine, Gabapentin, or Lamotrigine Versus an Unmatched Placebo Control Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015106

•

Does gabapentin and lamotriginel have significantly fewer side-effects while providing equal or better seizure control than the current drug choice, carbamazepine, for the treatment of seizures in the elderly. Condition(s): seizures in the elderly Study Status: This study is completed.

8

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; Parke-Davis; Glaxo Wellcome Purpose - Excerpt: New onset epilepsy in the elderly occurs in 45,000-50,000 elderly patients each year. These patients are especially vulnerable to side effects from medications because of changes caused by the aging process and the fact that these patients often have many common diseases for which they are already receiving medications for so that the likelihood of drug interactions is increased. Two new drugs, gabapentin and lamotrigine, have recently been approved by the FDA as antiepileptic drugs. These drugs have demonstrated efficacy in the treatment of partial onset seizures, the most common seizures in the elderly. These new compounds also have favorable side effect profiles and infrequent drug-drug interactions and, therefore, would be expected to be well-tolerated in the elderly. Phase(s): Phase III; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007670 •

Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer Condition(s): Quality of Life; neurotoxicity; Pain; unspecified adult solid tumor, protocol specific Study Status: This study is not yet open for patient recruitment. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Lamotrigine may be effective in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether lamotrigine is effective in treating peripheral neuropathy caused by chemotherapy. PURPOSE: Randomizedphase III trial to study the effectiveness of lamotrigine in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy caused by chemotherapy in patients who have cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068445

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “lamotrigine” (or synonyms).

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While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 4. PATENTS ON LAMOTRIGINE 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.9 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 “lamotrigine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lamotrigine, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Lamotrigine By performing a patent search focusing on lamotrigine, 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 9Adapted

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 lamotrigine: •

Methods for treating neurodegenerative diseases and disorders using N-(2,6disubstituted aromatic)-N'-pyridinyl ureas and other anticonvulsant compounds Inventor(s): Taylor, Jr.; Charles Price (Chelsea, MI), Weber; Mark Lawrence (Farmington Hills, MI) Assignee(s): Warner-lambert Company (morris Plains, Nj) Patent Number: 6,133,299 Date filed: February 25, 1993 Abstract: The instant invention is novel uses of known N-(2,6-disubstituted phenyl)-N'3- and 4-pyridinyl ureas and pharmaceutically acceptable acid addition salts thereof. Such compounds as N-(2-chloro-6-methylphenyl)-N'-4-pyridinyl urea monohydrochloride or N-(2,3-dichlorophenyl)-N'-4-pyridinyl urea are used for treating neurodegenerative disorders, perinatal asphyxia, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. The instant invention is similar novel uses of known anticonvulsant compounds as ralitoline, phenytoin, lamotrigine, tetrodotoxin, lidocaine, and carbamazepine. Excerpt(s): The present invention relates to novel therapeutic uses of a known compound, N-(2,6-disubstituted aromatic)-N'-pyridinyl ureas, its derivatives, and pharmaceutically acceptable salts. The present invention also relates to novel therapeutic uses of various other anticonvulsant drugs, their derivatives, and pharmaceutically acceptable salts. The present invention concerns a method for treating neurodegenerative diseases and disorders in a mammal in need of such treatment. Such neurodegenerative diseases are, for example, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. The present invention also covers treating neurodegenerative disorders termed acute brain injury. These include but are not limited to: stroke, head trauma, and asphyxia. Web site: http://www.delphion.com/details?pn=US06133299__

•

Pharmaceutical composition containing lamotrigine Inventor(s): Floyd; Alison Green (Raleigh, NC), Jain; Sunil (Cary, NC) Assignee(s): Glaxo Wellcome Inc. (research Triangle Park, Nc) Patent Number: 5,942,510 Date filed: December 9, 1997 Abstract: A lyophilized formulation of lamotrigine having been prepared by lyophilizing a frozen sterile aqueous solution of Imotrigine mesylate in which the pH is from 2.4 to 4. Excerpt(s): This application is filed pursuant to 35 U.S.C.sctn. 371 as a United States National Phase Application of International Application No. PCT/US96/02759 filed Jun. 20, 1996 which claims priority from GB9512854.2 filed Jun. 23, 1995. The present invention relates to a novel pharmaceutical formulation of lamotrigine, a process for its preparation, and its use in medical therapy. Status Epilepticus (SE) is a life-threatening condition in which the high morbidity and mortality rates are directly related to the

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duration of seizure activity. There exists a clinical need for an antiepileptic drug (AED) that may be administered rapidly and safely via the intravenous route to achieve therapeutic plasma concentrations for the treatment of SE. The only AED currently available in an intravenous formulation is phenytoin. However, recommended doses must be administered over a period of at least 20 minutes to avoid cardiovascular sideeffects (including tachycardia, bradycardia, hypotension and cardiac arrythmias) produced by the drug and its solvent, propylene glycol. Furthermore, intravenous phenytoin administration is commonly associated with injection site reactions including pain, inflammation and sclerosis. Web site: http://www.delphion.com/details?pn=US05942510__ •

Pharmaceutical composition of lamotrigine Inventor(s): Hiskett; Simon Philip (Kent, GB), Taylor; Susan Ann (Kent, GB) Assignee(s): The Wellcome Foundation Limited (middlesex, Gb3) Patent Number: 5,861,179 Date filed: June 26, 1997 Abstract: The present invention relates to a pharmaceutical formulation of lamotrigine, pharmaceutically acceptable salts thereof and the preparation of such a formulation. Excerpt(s): This application is a 371 of PCT/GB45/02865 filed Dec. 7, 1995. The present invention relates to a pharmaceutical formulation of lamotrigine and pharmaceutically acceptable acid addition salts thereof. The invention also relates to the preparation of such a formulation. Lamotrigine is 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine. It is disclosed in EP-A-0021121. Lamotrigine is useful for the treatment of epilepsy. No powder formulation of lamotrigine or one of its salts is currently available. Web site: http://www.delphion.com/details?pn=US05861179__

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Use of lamotrigine for treating AIDS-related neural disorders Inventor(s): Bousseau; Anne (Paris, FR), Doble; Adam (Paris, FR), Louvel; Erik (Paris, FR) Assignee(s): Rhone-poulenc Rorer S.a. (antony, Fr) Patent Number: 5,629,312 Date filed: September 1, 1995 Abstract: The use of lamotrigine or pharmaceutically acceptable salts thereof for treating AIDS-related neuronal disorders is disclosed. Excerpt(s): The present invention relates to a novel therapeutic application of lamotrigine or the pharmaceutically acceptable salts of this compound. Lamotrigine or the pharmaceutically acceptable salts of this compound are described as anticonvulsants and antiepileptics, in particular in Patent EP 247,892. It has now been found, surprisingly, that this compound may also be used in the treatment of neuro-AIDS. Web site: http://www.delphion.com/details?pn=US05629312__

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Water-dispersible tablets Inventor(s): Fielden; Krystyna E. (Dartford, GB) Assignee(s): Glaxo Wellcome Inc. (research Triangle Park, Nc) Patent Number: 5,556,639 Date filed: July 13, 1993 Abstract: A water-dispersible tablet comprises lamotrigine, a pharmaceutically acceptable swellable clay and an additional disintegrating agent. The swellable clay and an additional disintegrating agent. The swellable clay is a smectite, e.g. Veegum F or bentonite, and is present within the granules of the tablet to provide a tablet which is capable of dispersing in water within 3 minutes to provide a dispersion which will pass through a 710.mu.m sieve. The tablet can be optionally film-coated in which case the dispersion time is less than 5 minutes. Excerpt(s): The present invention relates to a water-dispersible tablet formulation containing a therapeutically active compound. Therapeutically active compounds or drugs are frequently administered to patients in tablet form where the drug is intended for oral administration since tablets are an especially convenient pharmaceutical form for manufacture, storage and generally usage. However, problems, may arise with the administration of such tablets to patients who have difficulty in swallowing the tablets (for example, children or more seriously ill patients) especially if the tablets are large in size arising from the amount of drug required in each tablet. A solution to such problems is to formulate the tablets in a form whereby they can be dispersed in water to form a dispersion containing the drug which can then be drunk by the patient. Known water-dispersible tablets include effervescent formulations which rely on the formation of a gas to quickly break up the tablet, but these involve expensive methods of manufacture and strict regulations for such manufacture. Other known waterdispersible tablets use disintegrating agents such as microcrystalline cellulose used in Feldene.RTM. R dispersible tablets. We have tested well-known disintegrating agents (incorporated both internally and externally to the preformed granules) such as sodium starch glycollate (e.g. Explotab), cross-linked povidone (e.g. Kollidon CL) and a crosslinked sodium carboxymethylcellulose (e.g. Ac-Di-Sol) in an acyclovir tablet, but found that they did not provide a satisfactory water-dispersible formulation. We furthermore tested an ion exchange resin (Amberlite 1RP88) as a disintegrating agent and incorporated surface active agents (e.g. sodium lauryl sulphate and sodium docusate) in an attempt to improve tablet wetting and penetrating of water during dispersion, but in all cases the disintegration time was high. Web site: http://www.delphion.com/details?pn=US05556639__

Patent Applications on Lamotrigine As of December 2000, U.S. patent applications are open to public viewing.10 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 lamotrigine:

10

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

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•

Compound and its use Inventor(s): Edmeades, Lorraine Mary; (Bishops Statford, GB), Griffith-Skinner, Nigel Arthur; (Dartford, GB), Hill, Derek Anthony; (Sittingbourne, GB), Hill, Graham Thronton; (Hertfort, GB), Packham, Terence William; (Dartford, GB) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20020055177 Date filed: August 29, 2001 Abstract: A method of testing the purity or stability to degradation of a sample of lamotrigine or a pharmaceutical dosage form comprising lamotrigine comprises assaying the said sample for the presence of a compound selected from 3-amino-6-(2,3dichlorophenyl)-1,2,4-triazine-5-(4H)-one (compound A) and N-[5-amino-6-(2,3dichlorophenyl)-1,2,4-triazine-3-yl]-2- ,3-dichlorobenzamide (compound B). A process for producing compound B, which is novel, is also disclosed. Excerpt(s): The present invention relates to compounds useful as reference markers for the analysis of lamotrigine and pharmaceutical formulations thereof. In order to secure marketing approval for a new drug product, a drugs manufacturer must submit detailed evidence to the appropriate regulatory authority to show that the product is suitable for release on to the market. The regulatory authority must be satisfied, inter alia, that the active agent is acceptable for administration to humans and that the particular formulation which is to be marketed is free from impurities at the time of release and has an appropriate shelf-life. Submissions made to regulatory authorities therefore typically include analytical data which demonstrate (a) that impurities are absent from the drug at the time of manufacture, or are present only at a negligible level, and (b) that the storage stability, i.e. shelf-life, of the drug is acceptable. These data are usually obtained by testing the drug against an external standard, or reference marker, which is a suitably pure sample of a potential impurity or a potential degradation product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Controlled release formulation of lamotrigine Inventor(s): Nadkarni, Sunil Sadanand; (Ahmedabad, IN) Correspondence: James V. Costigan, ESQ.; Hedman & Costigan, P.C.; Suite 2003; 1185 Avenue OF The Americas; New York; NY; 10036-2646; US Patent Application Number: 20040043996 Date filed: June 2, 2003 Abstract: Rapidly disintegrating multiparticulate controlled release formulations of lamotrigine having an improved pharmacokinetic profile and improved patient compliance, and process of preparing the formulations. It provides better control of blood plasma levels than conventional tablet formulations that is administered once or more times a day. Excerpt(s): The invention relates to rapidly disintegrating multiparticulate controlled release formulations of lamotrigine having an improved pharmacokinetic profile resulting in reduced dosing frequency. This invention further relates to a process for preparing the dosage form. Controlled release refers to the release of the therapeutically

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active agent from a composition or dosage form in which the agent is released according to a desired profile over an extended period of time. Controlled release profiles include, for example, sustained release, prolonged release, pulsatile release, and delayed release profiles. In contrast to immediate release compositions, controlled release compositions allow delivery of an agent to a subject over an extended period of time according to predetermined profile. Such release rates can provide therapeutically effective levels of an agent for an extended period of time and thereby provide a longer period of pharmacological or diagnostic response as compared to conventional rapid release dosage forms. Such longer periods of response provide for many inherent benefits that are not achieved with the corresponding short acting, immediate release preparations. For example, in the treatment of chronic pain, controlled release formulations are often highly preferred over conventional short-acting formulations. Controlled release pharmaceutical compositions and dosage forms are designed to improve the delivery profile of agents, such as drugs, medicaments, active agents, diagnostic agents, or any substance to be internally administered to an animal, including humans. A controlled release composition is typically used to improve the effects of administered substances by optimizing the kinetics of delivery, thereby increasing bio-availability, convenience, and patient compliance, as well as minimizing side effects associated with inappropriate immediate release rates such as high initial release rate and, if undesired, uneven blood or tissue levels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Crystal forms of lamotrigine and processes for their preparations Inventor(s): Aronhime, Judith; (Rehovot, IL), Berkovich, Yana; (Jerusalem, IL), Dolitzky, Ben-Zion; (Petach Tiqva, IL), Garti, Nissim; (Ramot, IL), Gershon, Neomi; (Rosh Ha-Ain, IL), Liebermann, Anita; (Tel-Aviv, IL), Singer, Claude; (Kfar Saba, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030018030 Date filed: February 27, 2002 Abstract: The present invention relates to lamotrigine, a useful agent for anti-epilepsia. New crystal forms of lamotrigine containing molecules of the solvent in stoichiometric ratios are disclosed. The present invention also provides processes for preparing the new crystal forms of lamotrigine. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn.1.19(e) of Provisional Application Serial No. 60/271,688, filed Feb. 27, 2001, the disclosure of which is incorporated by reference in its entirety herein. The present invention relates to new crystal forms of lamotrigine, related pharmaceutical composition, and processes for their preparation. Lamotrigine is an anti-epileptic drug of the phenyltriazine class and is chemically unrelated to other existing anti-epileptic drugs. This drug is produced by GlaxoWellcome and is sold under the trademark LAMICTAL.TM. LAMICTAL.TM. is produced in the form of chewable dispersible tablets and is available in different strengths (from 2 mg to 200 mg). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Method for producing lamotrigine from alpha-oxo-2,3-dichlorophenyl acetamidinoaminoguanidino hydrazone by ring closure reaction Inventor(s): Garaczi, Sandor; (Budapest, HU), Gego, Csaba Lehel; (Budapest, HU), Lukacs, Ferenc; (Kistarcsa, HU), Mate, Attila Gergely; (Budapest, HU), Nyerges, Miklos; (Budapest, HU), Ondi, Levente; (Budapest, HU), Schneider, Geza; (Budapest, HU) Correspondence: Shanks & Herbert; 1033 N. Fairfax Street; Suite 306; Alexandria; VA; 22314; US Patent Application Number: 20030191310 Date filed: May 15, 2003 Abstract: The present invention relates to a method for producing 3,5-diamino-6-(2,3dichlorophenyl)-1,2,4-triazine (lamotrigine) by cyclization reaction from.alpha.-oxo-2,3dichlorophenylacetamidino-amino- guanidino-hydrazone. Excerpt(s): The present invention relates to a method for producing Lamotrigine as well as intermediate products used in the method. This compound, disclosed for example in European patent publication EP-A-0 021 121, is suitable for treating disorders of the central nervous system, in particular epilepsy, and since 1990 has been used in spasmolytic medications in numerous countries. The methods disclosed in the aforementioned patent applications for producing lamotrigine by way of a cyclization reaction with a compound of formula II deviate in individual steps from the reaction sequence illustrated above. Common to all of them, however, is that the compound of formula (II) is obtained by reacting 2,3-dichlorobenzoyl cyanide (formula VI) with aminoguanidine. In accordance with the aforementioned patent applications 2,3dichlorobenzoyl cyanide is produced by reaction with copper cyanide from 2,3dichlorobenzoyl chloride (formula V). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of medicaments Inventor(s): Etheridge, Steven; (Harlow, NC) Correspondence: David J Levy, Corporate Intellectual Property; Glaxosmithkline; Five Moore DR., PO Box 13398; Research Triangle Park; NC; 27709-3398; US Patent Application Number: 20040023962 Date filed: August 14, 2003 Abstract: The present invention provides the use of frequency dependent voltage activated sodium channel blockers particularly lamotrigine in the prevention of noise induced hearing loss. Excerpt(s): The present invention relates to a new use of frequency dependent voltage activated sodium channel blockers. In particular, the present invention relates to a new use of 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,- 4-triazine and its pharmaceutically acceptable acid addition salts. Compounds exhibiting frequency dependent voltage activated sodium channel blocker activity include those described in EP-A-0021121, WO97/09317, WO98/38174, WO99/32462 and WO00/12488. Simpson et al., The Assessment of Lamotrigine, an Antieplileptic Drug, in The Treatment of Tinnitus, Am J Otol 1999; 20: p 627-631 suggests that lamotrigine might be useful in the treatment of tinnitus.

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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 lamotrigine, 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 “lamotrigine” (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 lamotrigine. You can also use this procedure to view pending patent applications concerning lamotrigine. 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 LAMOTRIGINE Overview This chapter provides bibliographic book references relating to lamotrigine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lamotrigine include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “lamotrigine” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on lamotrigine: •

Numb Toes and Aching Soles: Coping with Peripheral Neuropathy Source: San Antonio, TX: MedPress. 1999. 300 p. Contact: Available from MedPress. P.O. Box 691546, San Antonio, TX 78269. (888) 6339898. Website: www.medpress.com. PRICE: $19.95 for soft back book; $29.95 for case bound book; plus shipping and handling. ISBN 0967110726. Summary: This book serves as a resource for people who experience pain related to peripheral neuropathy. About one half of peripheral neuropathies are related to complications from diabetes mellitus. The book focuses on traditional, conventional, and alternative treatments for neuropathic pain. The book begins with a chapter that defines peripheral neuropathy and discusses this condition in terms of its types, symptoms and effects, causes, and evaluation. The next chapter explains the physical and psychological aspects of peripheral neuropathic pain. The following chapter discusses medications for treating peripheral neuropathic pain, including nonopioid drugs, opioids, and topical

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medications. A discussion of nonopioid drug costs is included. The fourth chapter focuses on other medical therapies for treating peripheral neuropathic pain, including hematologic treatments such as plasmapheresis, immunosuppressant medications, and nerve based treatments such as nerve blocks and direct nerve stimulation. This is followed by a chapter on alternative treatments, including physical therapy; psychotherapeutic methods such as relaxation and meditation training, biofeedback, self hypnosis, and prayer; hyperbaric oxygen therapy; acupuncture; touch therapies such as massage, reflexology, Reiki, Qigong, and therapeutic touch; magnets; and chelation. Treating peripheral neuropathic pain with various nutrients (vitamins A, B, C, and E; minerals such as selenium, magnesium, chromium, and zinc; and herbs such as ginkgo biloba, St. John's wart, bioflavonoids, and others) is the topic of the next chapter. In addition, the chapter provides information on other supplements such as alpha-lipoic acid, gamma linolenic acid, acetyl-L-carnitine, N-acetyl cysteine, glutamine, coenzyme Q10, S-adenosylmethionine, dimethyl sulfoxide, and methyl sulfonyl methane. The focus of the next chapter is on experimental or unapproved drugs, including aldose reductase inhibitors; aminoguanidine; COX-2; ABT-594; SNX-111; lamotrigine; memantine; natural pain relievers such as bimoclomol, cannabinoids, endorphins, and nocistatin/OFQ2; nerve regenerating compounds such as NGF, IGF-1, neutrophin-3, and GPI 1046; nimodipine; peptide T; and PN 401. This is followed by a chapter that examines diabetes and HIV. Diabetes classifications and diabetic neuropathy (types, risk factors, blood sugar control, and treatment approaches) are discussed. The final chapter presents ways of coping with peripheral neuropathy, including exercising, using heat or cold therapy, creating conducive conditions for sleeping, avoiding certain foods, and selecting appropriate footwear. The book concludes with an index.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “lamotrigine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “lamotrigine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “lamotrigine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Lamotrigine --A Brighter Future: Proceedings of a Conference Sponsored by Glaxo Wellcome, Held in Paris on 10-11 February 1995 by P. Loiseau; ISBN: 1853152838; http://www.amazon.com/exec/obidos/ASIN/1853152838/icongroupinterna

Chapters on Lamotrigine In order to find chapters that specifically relate to lamotrigine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and lamotrigine 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

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and language you prefer, and the format option “Book Chapter.” Type “lamotrigine” (or synonyms) into the “For these words:” box.

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

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

Glaxo's Lamictal drug wins wider U.S. approval Source: Reuters Industry Breifing Date: January 15, 2004

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Benefit of lamotrigine confirmed for HIV-associated neuropathic pain Source: Reuters Industry Breifing Date: May 30, 2003

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Lamotrigine has antidepressant effect in patients with bipolar disorder Source: Reuters Industry Breifing Date: May 02, 2003

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Lamictal gets FDA approval for treatment of partial seizures in children Source: Reuters Medical News Date: January 20, 2003

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Glaxo files Lamictal epilepsy drug for manic depression Source: Reuters Industry Breifing Date: August 29, 2002

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Lamotrigine dose adjustment required during pregnancy and postpartum Source: Reuters Medical News Date: July 30, 2002

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Lamotrigine protects against bipolar depression symptoms Source: Reuters Industry Breifing Date: May 22, 2002

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Lamotrigine maintains stable weight in teenagers with epilepsy Source: Reuters Industry Breifing Date: December 04, 2001

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Lamotrigine reduces diabetic neuropathy pain Source: Reuters Industry Breifing Date: August 24, 2001

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Label of GlaxoSmithKlines' Lamictal is revised to reflect lack of geriatric data Source: Reuters Industry Breifing Date: May 29, 2001

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Lamotrigine is good alternative to amitriptyline for central poststroke pain Source: Reuters Industry Breifing Date: January 22, 2001

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Lamotrigine effective mood stabilizer for some with rapid-cycling bipolar disorder Source: Reuters Industry Breifing Date: December 15, 2000

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Add-on lamotrigine reduces seizures in patients with severe partial epilepsy Source: Reuters Industry Breifing Date: November 21, 2000

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Case report adds to evidence of possible hepatotoxic side effects with lamotrigine Source: Reuters Industry Breifing Date: October 26, 2000

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Lamotrigine avoids weight gain seen with valproic acid Source: Reuters Industry Breifing Date: October 10, 2000

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Glaxo warns of Lamictal adverse events resulting from confusion with Lamisil Source: Reuters Industry Breifing Date: July 03, 2000

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Use of lamotrigine shows promise in relieving painful HIV-related neuropathy Source: Reuters Medical News Date: June 22, 2000

Periodicals and News

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Addition of lamotrigine, vigabatrin benefits children with refractory epilepsy Source: Reuters Medical News Date: December 10, 1999

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Lamotrigine effective as adjunctive therapy for partial epileptic seizures in children Source: Reuters Medical News Date: November 10, 1999

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Lamotrigine can induce tourettism Source: Reuters Medical News Date: April 27, 1999

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Lamotrigine prevents migraine aura in pilot study Source: Reuters Medical News Date: April 14, 1999

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FDA approves lamotrigine for treatment of epilepsy Source: Reuters Medical News Date: December 18, 1998

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Lamotrigine efficacious as monotherapy for patients with refractory epilepsy Source: Reuters Medical News Date: October 22, 1998

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Adjunctive lamotrigine approved by FDA for intractable pediatric epilepsy Source: Reuters Medical News Date: August 28, 1998

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Lamotrigine Reverses Valproate-Associated Hyperinsulinemia In Epileptic Women Source: Reuters Medical News Date: April 28, 1998

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Lamotrigine Effective In Lennox-Gastaut Syndrome Source: Reuters Medical News Date: December 18, 1997

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Adverse Effects Of Epilepsy Drug, Lamotrigine, Reported Source: Reuters Medical News Date: December 12, 1997

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Lamotrigine May Be Neuroprotective After Cardiac Arrest Source: Reuters Medical News Date: November 19, 1997

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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.

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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 “lamotrigine” (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 “lamotrigine” (or synonyms). If you know the name of a company that is relevant to lamotrigine, 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 “lamotrigine” (or synonyms).

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

Systemic - U.S. Brands: Lamictal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202786.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 Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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

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

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

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

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

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

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

11

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

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•

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

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

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

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

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

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

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

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

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

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

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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

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

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

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

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

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

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

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

12

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). 13 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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lamotrigine” (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 1548 3 28 5 4 1588

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “lamotrigine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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.

Physician Resources

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Coffee Break: Tutorials for Biologists19 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.20 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.21 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/.

19 Adapted 20

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. 21 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 lamotrigine 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 lamotrigine. 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 lamotrigine. 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 “lamotrigine”:

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Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Drug and Medical Device Safety http://www.nlm.nih.gov/medlineplus/drugandmedicaldevicesafety.html Epilepsy http://www.nlm.nih.gov/medlineplus/epilepsy.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to lamotrigine. 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

Patient Resources 99

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lamotrigine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lamotrigine. 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 lamotrigine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “lamotrigine” (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 “lamotrigine”. 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 “lamotrigine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “lamotrigine” (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.22

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

22

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)23: •

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/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 103

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries 105

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

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

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

•

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

•

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

•

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

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LAMOTRIGINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [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] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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

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intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]

Aldose Reductase Inhibitor: A class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes. Aldose reductase is an enzyme that is normally present in the eye and in many other parts of the body. It helps change glucose (sugar) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Drugs that prevent or slow (inhibit) the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] 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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [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] 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] 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]

Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [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] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] 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] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] 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

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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] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antiepileptic: An agent that combats epilepsy. [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] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Anti-Inflammatory Agents, Topical: Anti-inflammatory agents that are applied to the skin and whose pharmacological effect only occurs at the area of application. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU]

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Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [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] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] 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] Aspartate: A synthetic amino acid. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] 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] Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Autonomic: Self-controlling; functionally independent. [EU] 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

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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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bentonite: A colloidal, hydrated aluminum silicate that swells 12 times its dry size when added to water. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] 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] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] 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]

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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] 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] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [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] Bupivacaine: A widely used local anesthetic agent. [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] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH]

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Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [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] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage.

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Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] 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] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing 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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or

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transplantation to replace the work of the kidneys. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [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] 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] Clorazepate Dipotassium: A water-soluble benzodiazepine derivative effective in the treatment of anxiety. It has also muscle relaxant and anticonvulsant actions. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] 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] 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] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [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] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colitis: Inflammation of the colon. [NIH] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH]

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Community Mental Health Centers: Facilities which administer the delivery of psychologic and psychiatric services to people living in a neighborhood or community. [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] 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] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH]

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Constipation: Infrequent or difficult evacuation of feces. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [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 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] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU]

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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] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] 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] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [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.

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Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] 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] 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] 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] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [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] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can

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use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [NIH] 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Drug Costs: The amount that a health care institution or organization pays for its drugs. It is one component of the final price that is charged to the consumer (fees, pharmaceutical or prescription fees). [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dystonia: Disordered tonicity of muscle. [EU]

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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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [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] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]

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] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH]

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Epilepsia: An illusional seizure consisting of a rather sudden alteration of the patient's perceptions, indicative of a lesion in the temporal lobes. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethosuximide: An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] 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] Exfoliation: A falling off in scales or layers. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] 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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fever of Unknown Origin: Fever in which the etiology cannot be ascertained. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flatus: Gas passed through the rectum. [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

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antidepressants. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [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] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Genital: Pertaining to the genitalia. [EU] 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] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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

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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] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [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]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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] 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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] 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]

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Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [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] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] 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] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypomania: An abnormality of mood resembling mania (persistent elevated or expansive mood, hyperactivity, inflated self-esteem, etc.) but of lesser intensity. [EU]

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Hypotension: Abnormally low blood pressure. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a

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step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] 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, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interindividual: Occurring between two or more individuals. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

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] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA

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fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] LH: A small glycoprotein hormone secreted by the anterior pituitary. LH plays an important role in controlling ovulation and in controlling secretion of hormones by the ovaries and testes. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [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] 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]

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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] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] 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] 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] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] 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]

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Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesolimbic: Inner brain region governing emotion and drives. [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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] 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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum

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formed after disruption and centrifugation of cells. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] 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] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [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]

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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] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] 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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] 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] 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]

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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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [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] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and pro-

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opiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] 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] Pancreatic: Having to do with the pancreas. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH]

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Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] 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] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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]

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Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

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]

Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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]

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Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] 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] Povidone: A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander. [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] 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] Prescription Fees: The charge levied on the consumer for drugs or therapy prescribed under written order of a physician or other health professional. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] 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] 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] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the

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nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU]

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Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] 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]

Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] 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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] 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] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [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] 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] Reality Testing: The individual's objective evaluation of the external world and the ability

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to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] 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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [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] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and

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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 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] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self-Injurious Behavior: Behavior in which persons hurt or harm themselves without the motive of suicide or of sexual deviation. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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]

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Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Skeletal: Having to do with the skeleton (boney part of the body). [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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmolytic: Checking spasms; antispasmodic. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with

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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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] 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] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] 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]

Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Sterile: Unable to produce children. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] 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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [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] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH]

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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]

Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] 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] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] 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] 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] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH]

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Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [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] 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] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] 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

Dictionary 149

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] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] 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] 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] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy.

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The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) 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] 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verbal Behavior: Includes both producing and responding to words, either written or spoken. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] 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] Wart: A raised growth on the surface of the skin or other organ. [NIH]

Dictionary 151

Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] 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] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH]

153

INDEX A Acetaldehyde, 109, 123 Acetaminophen, 12, 36, 109 Acetylcholine, 109, 117, 136 Activities of Daily Living, 10, 109 Acyclovir, 72, 109 Adaptability, 109, 116 Adjunctive Therapy, 37, 83, 109 Adjustment, 82, 109 Adrenal Cortex, 109, 120 Adrenergic, 11, 109, 111, 112, 123, 125, 147 Adverse Effect, 83, 109, 118, 123, 145 Aerosol, 109, 147 Affinity, 109, 110, 113, 118, 122, 145 Age Groups, 8, 110 Aged, 80 and Over, 110 Agonist, 9, 11, 110, 113, 115, 123, 134 Akathisia, 110, 112 Aldehyde Dehydrogenase, 110, 123 Aldose Reductase Inhibitor, 78, 110 Algorithms, 110, 114 Alkaloid, 110, 115, 116, 118, 134 Alpha-1, 110, 111 Alternative medicine, 84, 110 Aluminum, 110, 114 Amantadine, 9, 110, 133 Amenorrhea, 110, 115 Amino Acids, 110, 138, 141, 147, 149 Amitriptyline, 82, 110 Ammonia, 111, 127, 149 Amphetamine, 111, 132 Amygdala, 63, 111, 131, 148 Amyotrophy, 42, 111 Anal, 111, 132 Analgesic, 19, 35, 109, 111, 124, 134, 137 Analog, 109, 111, 131 Anatomical, 111, 129, 144 Androgens, 32, 109, 111, 120 Anesthesia, 111, 131, 140 Angina, 111, 130 Angina Pectoris, 111, 130 Animal model, 9, 111 Anions, 111, 130, 145, 147 Antagonism, 111, 118 Antiallergic, 111, 120 Antibacterial, 111, 146 Antibiotic, 111, 146 Antibodies, 111, 112, 127, 132

Antibody, 109, 112, 127, 128, 129, 142 Anticholinergic, 110, 112 Anticonvulsant, 3, 13, 17, 47, 60, 63, 70, 112, 116, 118, 125, 149 Antidepressant, 82, 110, 112, 115, 125 Antiemetic, 112 Antiepileptic, 6, 8, 12, 20, 31, 33, 34, 40, 42, 43, 44, 50, 56, 60, 62, 66, 71, 112 Antigen, 109, 112, 128, 129, 142 Anti-inflammatory, 11, 109, 112, 120, 126 Anti-Inflammatory Agents, 11, 112, 120 Anti-Inflammatory Agents, Topical, 11, 112 Antimetabolite, 109, 112 Antineoplastic, 112, 120 Antipsychotic, 19, 112, 118, 135 Antipyretic, 109, 112 Antispasmodic, 113, 137, 145 Antiviral, 109, 110, 113 Anxiety, 110, 113, 118 Apoptosis, 6, 113 Aqueous, 70, 113, 114, 121, 128 Arginine, 113, 136 Aromatic, 70, 113 Arterial, 113, 120, 126, 128, 141 Arteries, 113, 114, 115, 120, 133 Arterioles, 113, 115, 116 Aspartate, 11, 15, 19, 113, 131 Asphyxia, 6, 70, 113 Assay, 33, 53, 55, 113, 142 Astrocytes, 6, 113 Atmospheric Pressure, 113, 128 Atrial, 113, 120, 147 Atrophy, 113, 135 Atypical, 49, 113, 118 Auditory, 113, 125 Aura, 27, 83, 113 Autonomic, 109, 112, 113, 136, 138, 146 B Baclofen, 7, 9, 113 Bacteria, 111, 112, 114, 119, 133, 146, 149 Basal Ganglia, 6, 112, 114, 117, 131, 142 Base, 7, 114, 122, 130, 147 Benign, 45, 49, 114 Bentonite, 72, 114 Bewilderment, 114, 119 Bilateral, 28, 114 Bile, 114, 126, 132

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Lamotrigine

Bioavailability, 49, 114 Biochemical, 6, 112, 114, 144 Biomarkers, 12, 114 Biotechnology, 14, 84, 93, 114 Biotransformation, 12, 114 Bipolar Disorder, 5, 13, 15, 18, 20, 21, 31, 38, 40, 45, 47, 50, 53, 55, 61, 82, 98, 114 Bladder, 114, 141, 149 Blood pressure, 114, 117, 126, 128, 129, 136, 145 Blood vessel, 114, 115, 116, 117, 120, 124, 126, 132, 138, 139, 145, 146, 148, 150 Blood Volume, 115, 140 Body Fluids, 114, 115, 145, 149 Body Image, 115, 122 Bone Marrow, 115, 132, 145 Bone scan, 115, 144 Bowel, 111, 115, 123, 131 Bowel Movement, 115, 123 Bradycardia, 71, 115 Bradykinin, 115, 136 Branch, 63, 105, 115, 132, 137, 146, 148 Breakdown, 115, 122, 126 Bromocriptine, 9, 115 Bupivacaine, 115, 131 Bupropion, 7, 9, 28, 115 C Calcium, 115, 130, 136 Cannabidiol, 115 Cannabinoids, 78, 115 Cannabinol, 115, 116 Cannabis, 5, 115, 116, 148 Capillary, 55, 115, 116, 150 Capsaicin, 11, 116 Capsules, 116, 123 Carbamazepine, 3, 8, 9, 11, 12, 15, 20, 21, 24, 25, 26, 28, 31, 38, 40, 41, 43, 44, 63, 65, 70, 116 Carbohydrate, 116, 120, 126, 139 Carboxymethylcellulose, 72, 116 Carcinogenic, 116, 130 Carcinogens, 116, 117 Cardiac, 6, 71, 83, 116, 120, 125, 130, 131, 134, 143 Cardiac arrest, 6, 116 Cardiovascular, 71, 111, 116, 144 Carnitine, 78, 116 Carrier Proteins, 116, 142 Case report, 24, 30, 51, 82, 116 Catecholamine, 116, 123, 138 Cauda Equina, 116, 144 Cell Death, 6, 12, 113, 116, 135

Cellobiose, 116, 117 Cellulose, 72, 117, 139 Central Nervous System, 75, 109, 111, 117, 118, 125, 126, 127, 134, 139, 144 Centrifugation, 117, 134 Cerebellar, 51, 117, 149 Cerebellar Diseases, 117, 149 Cerebellum, 117 Cerebral, 6, 41, 114, 117, 120, 122, 125, 126, 141, 147, 148 Cerebral Palsy, 6, 117 Cerebrovascular, 117, 136 Cerebrum, 117, 147 Chelation, 78, 117 Chemoreceptor, 112, 117 Chemotherapy, 66, 117 Cholinergic, 111, 112, 117 Chorea, 112, 117 Chromatin, 113, 117 Chromium, 78, 117 Chromosomal, 57, 117 Chronic, 10, 11, 14, 16, 23, 27, 53, 60, 74, 117, 122, 124, 129, 130, 146 Chronic renal, 23, 117 Cimetidine, 28, 118 Clinical trial, 4, 5, 7, 10, 20, 39, 50, 65, 67, 93, 118, 120, 141, 142 Cloning, 114, 118 Clorazepate Dipotassium, 4, 118 Clozapine, 21, 29, 39, 51, 118 Coagulation, 41, 115, 118 Coca, 118 Cocaine, 5, 7, 9, 38, 65, 118, 132 Cochlear, 118, 148, 150 Cochlear Diseases, 118, 148 Coenzyme, 78, 118 Cognition, 27, 51, 118, 135 Colitis, 17, 118 Colloidal, 114, 118, 124, 125, 145, 147 Combination Therapy, 5, 26, 55, 118 Community Mental Health Centers, 5, 119 Comorbidity, 55, 119 Computational Biology, 93, 119 Computed tomography, 119, 144 Computerized axial tomography, 119, 144 Concomitant, 44, 51, 60, 119 Conduction, 119, 148 Confusion, 82, 119, 123, 135 Congestion, 112, 119 Conjugated, 12, 119, 121 Conjugation, 114, 119, 127 Conjunctiva, 119, 149

Index 155

Conjunctivitis, 57, 119 Connective Tissue, 115, 119, 125, 126, 143 Consciousness, 51, 111, 119, 121, 122, 143, 146 Constipation, 112, 120 Contamination, 120, 127, 128 Contraindications, ii, 120 Controlled study, 16, 19, 120 Convulsions, 112, 120 Convulsive, 43, 120 Cor, 120, 126, 140 Coronary, 111, 120, 133 Coronary Thrombosis, 120, 133 Cortex, 6, 120, 124, 125 Cortical, 23, 120, 125, 144 Corticosteroid, 10, 120 Cranial, 33, 117, 120, 121, 130, 135, 138, 149, 150 Craniocerebral Trauma, 121, 148 Cultured cells, 13, 121 Curative, 121, 148 Cutaneous, 12, 121, 137 Cyanide, 75, 121 Cyclic, 121, 127, 136 Cysteine, 78, 121, 147 Cystine, 121 Cytochrome, 12, 118, 121 Cytoplasm, 113, 121 D Data Collection, 7, 121 Databases, Bibliographic, 93, 121 Deamination, 121, 149 Degenerative, 121, 127, 134, 143 Deletion, 113, 121, 126 Delirium, 112, 121 Delusions, 122, 141 Dementia, 18, 112, 122 Dendrites, 122, 135 Dentate Gyrus, 122, 128 Depersonalization, 17, 38, 122, 144 Depressive Disorder, 122, 132 Deprivation, 6, 122 Derealization, 122 Desipramine, 9, 122 Detoxification, 11, 12, 122 Diabetes Insipidus, 33, 122 Diabetes Mellitus, 77, 122, 127 Diagnostic procedure, 69, 84, 122 Diencephalon, 122, 147, 148 Digestion, 114, 115, 122, 132, 146 Digestive system, 67, 122 Dimethyl, 78, 123, 130

Direct, iii, 4, 10, 78, 87, 123, 143 Disorientation, 119, 121, 123 Distal, 123, 138 Disulfiram, 7, 123 Dopamine, 9, 110, 111, 112, 115, 118, 123, 132 Dosage Forms, 74, 123 Drug Costs, 78, 123 Drug Interactions, 8, 12, 61, 66, 88, 123 Drug Monitoring, 24, 25, 32, 33, 35, 40, 43, 44, 46, 50, 54, 55, 123 Drug Tolerance, 123, 148 Drug Toxicity, 13, 123 Dyskinesia, 112, 123 Dystonia, 112, 123 E Efficacy, 4, 5, 9, 10, 11, 12, 20, 21, 28, 29, 35, 36, 43, 45, 47, 53, 60, 62, 66, 124 Elective, 124, 145 Electrocoagulation, 118, 124 Electrolyte, 120, 122, 124, 134, 140, 145 Electrons, 114, 124, 130, 132, 137, 142 Electrophoresis, 55, 124 Elementary Particles, 124, 132, 141 Empiric, 6, 124 Endocrine System, 124, 135 Endorphin, 124, 126 Endothelium, 124, 136 Endothelium-derived, 124, 136 End-stage renal, 117, 124 Entorhinal Cortex, 124, 128 Environmental Health, 92, 94, 124 Enzyme, 12, 110, 118, 124, 127, 133, 138, 141, 143, 147, 149, 150 Epidermal, 30, 31, 47, 52, 124 Epidermis, 124 Epinephrine, 109, 123, 125, 136, 149 Ergot, 115, 125 Esophagus, 123, 125, 146 Ethosuximide, 4, 6, 30, 42, 125 Evoked Potentials, 27, 125 Excitability, 23, 125 Excitatory, 114, 125, 127 Exfoliation, 125, 135 Exogenous, 27, 114, 125, 127, 141 Expander, 125, 140 Extracellular, 6, 113, 119, 125, 133, 145 Extracellular Space, 6, 125, 133 Extraction, 50, 125 Extrapyramidal, 110, 112, 123, 125 F Family Planning, 93, 125

156

Lamotrigine

Fat, 115, 120, 125, 126, 131, 143 Fatty acids, 125, 127 Fever of Unknown Origin, 54, 125 Fibrosis, 125, 144 Flatus, 125, 126 Fluoxetine, 15, 125 Flushing, 123, 126 Frontal Lobe, 26, 126 G Gallbladder, 123, 126 Gamma-Endorphin, 126 Gas, 24, 33, 72, 111, 125, 126, 128, 136, 147 Gastric, 116, 118, 123, 126, 128, 138 Gastric Acid, 118, 126 Gastrin, 118, 126, 128 Gene, 6, 114, 126 Gene Deletion, 6, 126 Genital, 31, 126 Geriatric, 39, 82, 126 Gestation, 126, 138 Ginkgo biloba, 78, 126 Glioma, 18, 126 Globus Pallidus, 126, 142 Glomerulus, 126, 135 Glucocorticoids, 10, 109, 120, 126 Gluconeogenesis, 126 Glucose, 110, 116, 117, 122, 126, 127, 130, 145 Glucose Intolerance, 122, 126 Glucuronosyltransferase, 8, 127 Glutamate, 6, 7, 9, 10, 11, 14, 15, 41, 127, 139 Glutamic Acid, 127 Glutamine, 78, 127 Glutathione Peroxidase, 127, 144 Glycogen, 13, 126, 127 Glycogen Synthase, 13, 127 Glycoprotein, 127, 131 Governing Board, 127, 140 Grade, 18, 127 Growth, 12, 43, 61, 111, 113, 116, 127, 135, 139, 150 Guanylate Cyclase, 127, 136 H Haptens, 109, 127, 142 Heme, 121, 127 Hemorrhage, 121, 124, 127, 146 Hepatic, 8, 30, 31, 122, 127 Hepatitis, 17, 127, 128 Hepatitis A, 17, 127 Hepatocytes, 127 Hepatotoxic, 82, 128

Hepatotoxicity, 12, 47, 128 Hepatovirus, 127, 128 Heredity, 126, 128 Herpes, 109, 128 Hippocampus, 10, 122, 128, 131, 146 Histamine, 112, 118, 128 Homologous, 128, 147 Hormonal, 113, 120, 128 Hormone, 32, 120, 125, 126, 128, 130, 131, 140, 143 Hydrogen, 114, 116, 127, 128, 134, 137, 141, 147, 151 Hydrogen Peroxide, 127, 128, 147 Hydrolysis, 114, 117, 128 Hyperaemia, 119, 128 Hyperbaric, 78, 128 Hyperbaric oxygen, 78, 128 Hypersensitivity, 17, 20, 32, 41, 42, 46, 47, 62, 128, 143 Hypertension, 120, 128, 130 Hypomania, 4, 33, 128 Hypotension, 71, 112, 120, 123, 129 Hypothermia, 6, 129 Hypoxia, 6, 122, 129 I Id, 64, 98, 104, 106, 129 Idiopathic, 29, 54, 129 Immune response, 12, 112, 120, 127, 129, 147, 150 Immune system, 129, 132, 149, 151 Immunodeficiency, 47, 54, 129 Immunogenic, 129, 142 Immunosuppressant, 78, 129 Impairment, 22, 114, 121, 123, 129, 133, 141 In vitro, 8, 12, 13, 33, 55, 62, 129 In vivo, 12, 13, 55, 62, 129, 133 Indicative, 78, 125, 129, 137, 150 Induction, 111, 112, 129, 131, 140 Infant, Newborn, 110, 129 Infarction, 120, 129, 133 Infection, 10, 122, 129, 132, 136, 143, 146, 151 Infertility, 115, 129 Inflammation, 71, 112, 118, 119, 125, 127, 129, 135, 143, 146 Informed Consent, 36, 129 Initiation, 12, 129, 132 Inotropic, 123, 130 Insight, 11, 14, 130 Insomnia, 48, 130 Insulin, 57, 130, 131

Index 157

Insulin-dependent diabetes mellitus, 130 Interindividual, 12, 130 Interstitial, 17, 125, 130, 135 Intervertebral, 130, 142, 144 Intervertebral Disk Displacement, 130, 142, 144 Intoxication, 122, 130, 151 Intracellular, 129, 130, 136, 140, 144 Intracranial Hypertension, 130, 148 Intramuscular, 11, 130 Intravascular, 41, 130 Intravenous, 9, 71, 130 Invasive, 130, 132 Involuntary, 117, 130, 134, 143, 145 Ion Channels, 113, 130, 136 Ion Exchange, 72, 117, 130 Ions, 114, 124, 128, 130, 134, 145 Isradipine, 7, 130 K Kb, 92, 130 Ketamine, 19, 131 Ketone Bodies, 131 Ketosis, 4, 131 Kinetic, 8, 36, 131 L Lamivudine, 54, 131 Large Intestine, 123, 131, 143 Laxative, 116, 131, 145 Lesion, 125, 131, 132, 147 Lethal, 121, 131 LH, 56, 131 Libido, 111, 131 Library Services, 104, 131 Lidocaine, 70, 131 Life cycle, 5, 131 Limbic, 111, 131 Limbic System, 111, 131 Lipid, 130, 131 Lithium, 4, 5, 13, 16, 18, 45, 51, 53, 112, 132 Liver, 8, 33, 109, 114, 116, 123, 126, 127, 128, 132, 144, 148, 149 Liver scan, 132, 144 Loading dose, 23, 132 Localization, 6, 132 Localized, 129, 132, 139 Longitudinal study, 5, 18, 132 Lymphatic, 124, 129, 132, 145 Lymphatic system, 132, 145 Lymphocyte, 62, 112, 132 M Magnetic Resonance Imaging, 62, 132, 144

Magnetic Resonance Spectroscopy, 62, 132 Mania, 5, 35, 61, 128, 132 Manic, 16, 82, 112, 114, 132, 141 Manic-depressive psychosis, 132, 141 Mastication, 132, 149 Mazindol, 9, 132 Mediate, 123, 133 Medical Records, 133, 143 MEDLINE, 93, 133 Medullary, 133, 142 Meiosis, 133, 147 Memantine, 11, 78, 133 Membrane, 113, 119, 125, 130, 133, 145 Membrane Glycoproteins, 133, 145 Memory, 6, 10, 121, 122, 133 Meninges, 117, 121, 133 Mental Disorders, 67, 133, 141 Mental Health, iv, 4, 61, 63, 67, 92, 94, 133 Mental Retardation, 6, 37, 44, 46, 133 Mesolimbic, 112, 133 Metabolic disorder, 122, 133 Metabolite, 8, 9, 12, 114, 123, 133 Methionine, 123, 133, 140, 147 MI, 25, 49, 52, 70, 107, 133 Microbe, 133, 148 Microbiology, 113, 133 Microdialysis, 6, 133 Microorganism, 133, 150 Microsomal, 8, 133 Mineralocorticoids, 109, 120, 134 Mitochondrial Swelling, 134, 135 Mitosis, 113, 134 Modeling, 8, 134 Modification, 134, 142, 151 Molecular, 20, 93, 95, 114, 119, 122, 125, 134, 140, 147, 149 Molecular Structure, 134, 149 Molecule, 112, 114, 118, 124, 128, 134, 137, 143, 149 Monotherapy, 4, 15, 16, 18, 21, 25, 28, 32, 38, 39, 40, 42, 43, 46, 55, 57, 83, 134 Mood Disorders, 10, 16, 37, 48, 61, 134 Morphine, 62, 134, 137 Morphological, 6, 63, 134 Movement Disorders, 110, 112, 134 Muscle relaxant, 118, 134 Myocardium, 111, 133, 134 Myoclonus, 25, 42, 45, 134 N Naloxone, 11, 52, 134 Narcotic, 109, 134

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Lamotrigine

Nausea, 112, 123, 131, 135 NCI, 1, 66, 67, 91, 135 Necrolysis, 30, 31, 47, 52, 135 Necrosis, 30, 113, 129, 133, 135 Need, 3, 5, 70, 71, 77, 78, 99, 117, 127, 135, 148 Neonatal, 6, 29, 135 Neostriatum, 135, 142 Nephritis, 17, 135 Nerve, 11, 39, 78, 109, 110, 111, 116, 122, 135, 138, 140, 142, 144, 146, 149, 150 Nerve Growth Factor, 11, 135 Nervous System, 111, 117, 135, 136, 138, 147 Neural, 11, 19, 71, 122, 135, 145 Neuralgia, 20, 39, 135, 139 Neurodegenerative Diseases, 70, 135 Neuroendocrine, 41, 135 Neuroleptic, 110, 112, 118, 135 Neuromuscular, 109, 135, 148 Neuronal, 6, 71, 135 Neurons, 6, 62, 118, 122, 125, 134, 135, 136, 146, 147, 150 Neuropathy, 10, 16, 37, 66, 77, 82, 110, 111, 136, 138, 144 Neurotoxicity, 66, 136 Neurotransmitters, 111, 136 Nimodipine, 78, 136 Nitric Oxide, 6, 136 Nitrogen, 110, 111, 127, 136 Norepinephrine, 109, 111, 122, 123, 136 Nuclear, 114, 119, 124, 131, 135, 136, 148 Nuclei, 6, 111, 119, 124, 131, 132, 134, 136, 141, 150 Nucleus, 113, 117, 121, 124, 126, 130, 133, 135, 136, 141, 142, 148, 150 O Odds Ratio, 21, 136 Odour, 113, 136 Ointments, 123, 136 Opioid Peptides, 136 Opium, 134, 137 Orthostatic, 112, 137 Outpatient, 5, 7, 137 Ovaries, 131, 137, 145, 148 Ovulation, 131, 137 Ovum, 126, 131, 137, 140 Oxidation, 114, 121, 127, 137 Oxidation-Reduction, 114, 137 P Paediatric, 20, 37, 54, 61, 137 Palliative, 137, 148

Pancreas, 114, 123, 130, 137, 149 Pancreatic, 116, 137 Paralysis, 109, 137, 148 Paresthesia, 137, 148 Parkinsonism, 112, 137 Paroxysmal, 26, 27, 56, 111, 113, 137 Patch, 46, 137 Pathologic, 113, 120, 128, 137, 150 Pathologic Processes, 113, 137 Pathophysiology, 13, 138 Patient Compliance, 73, 74, 138 Patient Satisfaction, 5, 138 Pepsin, 118, 138 Pepsin A, 118, 138 Peptide, 78, 126, 137, 138, 140, 141 Perception, 122, 138, 144 Perfusion, 7, 55, 129, 138 Perinatal, 70, 138 Peripheral Nervous System, 135, 138, 147 Peripheral Neuropathy, 66, 77, 138, 151 Pharmaceutical Preparations, 117, 138, 141 Pharmaceutical Solutions, 123, 138 Pharmacodynamic, 11, 13, 20, 62, 138 Pharmacokinetic, 7, 13, 17, 20, 40, 45, 56, 73, 138 Pharmacologic, 10, 111, 138, 148 Pharmacotherapy, 9, 22, 28, 30, 31, 38, 49, 52, 138 Phenobarbital, 3, 6, 21, 24, 139 Phenotype, 126, 139 Phenyl, 70, 139 Phosphorylated, 118, 139 Photocoagulation, 118, 139 Physical Therapy, 78, 139 Physiologic, 110, 134, 139, 143, 147, 149 Pilot Projects, 5, 139 Pilot study, 4, 27, 83, 139 Pituitary Gland, 120, 139, 140 Plants, 110, 118, 126, 136, 139, 149 Plasma, 20, 24, 27, 29, 32, 33, 37, 39, 43, 44, 56, 71, 73, 112, 115, 125, 126, 134, 139, 145 Plasmapheresis, 78, 139 Platelet Aggregation, 136, 139 Platelets, 136, 139, 144 Poisoning, 122, 123, 125, 130, 135, 139 Polysaccharide, 112, 117, 139 Posterior, 111, 117, 137, 139, 144 Postherpetic Neuralgia, 110, 139 Post-synaptic, 11, 140 Potassium, 62, 134, 140

Index 159

Potentiates, 122, 140 Potentiating, 111, 140 Povidone, 72, 140 Practice Guidelines, 94, 140 Precursor, 123, 126, 136, 140, 149 Prescription Fees, 123, 140 Prevalence, 5, 8, 136, 140 Probe, 133, 140 Procaine, 131, 140 Progression, 6, 34, 111, 140 Progressive, 30, 117, 122, 123, 127, 135, 140 Prolactin, 115, 140 Prone, 12, 140 Pro-Opiomelanocortin, 126, 137, 140 Prophase, 140, 147 Prophylaxis, 4, 15, 27, 141 Propylene Glycol, 71, 141 Prospective study, 23, 47, 132, 141 Prostate, 114, 141, 149 Protease, 118, 141 Protein Binding, 12, 141 Protein C, 141, 149 Protein S, 114, 141 Proteins, 110, 112, 116, 117, 134, 136, 138, 139, 141, 145, 148 Protocol, 7, 66, 141 Protons, 128, 132, 141, 142 Psychiatric, 55, 119, 133, 141 Psychic, 131, 141, 144 Psychomotor, 116, 121, 135, 141 Psychosis, 27, 112, 141 Psychotropic, 46, 142 Public Policy, 93, 142 Publishing, 14, 142 Putamen, 6, 135, 142 Q Quality of Life, 5, 10, 15, 22, 66, 142 Quaternary, 36, 142 R Race, 13, 142 Radiation, 111, 124, 128, 142, 144, 151 Radiation therapy, 128, 142 Radiculopathy, 142, 144 Radioactive, 115, 128, 132, 136, 142, 144 Radioimmunoassay, 56, 142 Randomized, 4, 7, 9, 10, 15, 17, 34, 38, 39, 48, 53, 124, 142 Randomized clinical trial, 7, 15, 34, 142 Reality Testing, 141, 142 Receptor, 9, 11, 19, 28, 61, 112, 117, 118, 123, 125, 139, 142, 143, 144 Rectum, 115, 123, 125, 126, 131, 141, 143

Recurrence, 49, 114, 132, 143 Reductase, 110, 143 Refer, 1, 126, 128, 132, 135, 141, 143 Reflex, 78, 143 Refraction, 143, 146 Refractory, 16, 21, 29, 31, 33, 35, 37, 39, 50, 53, 57, 62, 83, 124, 143 Regimen, 124, 138, 143 Remission, 114, 132, 143 Respiration, 117, 143 Restoration, 139, 143 Resuscitation, 6, 143 Retinopathy, 110, 139, 143 Retrospective, 29, 35, 46, 143 Retrospective study, 35, 143 Rheumatism, 143 Rheumatoid, 10, 143 Rheumatoid arthritis, 10, 143 Risk factor, 78, 141, 143 S Salivary, 123, 143 Salivary glands, 123, 143 Scans, 10, 143 Schizoid, 144, 151 Schizophrenia, 5, 19, 21, 38, 39, 144, 151 Schizotypal Personality Disorder, 122, 144, 151 Sciatica, 37, 144 Sclerosis, 15, 70, 71, 144 Screening, 7, 8, 9, 118, 144 Secretion, 115, 118, 120, 126, 128, 130, 131, 134, 144 Sedative, 110, 144 Seizures, 3, 6, 16, 18, 23, 25, 26, 28, 29, 30, 54, 56, 61, 62, 63, 65, 66, 82, 83, 116, 122, 125, 137, 144, 146 Selenium, 78, 144 Self Care, 109, 144 Self-Injurious Behavior, 44, 144 Semisynthetic, 115, 144 Sequencing, 12, 144, 147 Serotonin, 111, 112, 118, 122, 125, 138, 144, 145 Sertraline, 7, 145 Serum, 13, 24, 25, 43, 44, 47, 50, 61, 62, 134, 142, 145 Serum Albumin, 142, 145 Sex Characteristics, 111, 145 Shock, 11, 134, 145, 149 Side effect, 3, 5, 21, 55, 66, 74, 82, 87, 109, 110, 112, 132, 145, 148, 151 Skeletal, 111, 145

160

Lamotrigine

Smooth muscle, 128, 130, 134, 145, 147 Social Environment, 142, 145 Sodium, 11, 25, 30, 32, 35, 62, 63, 72, 75, 134, 145, 150 Sodium Channels, 11, 145, 150 Solid tumor, 66, 145 Solvent, 71, 74, 138, 141, 145 Somatic, 131, 133, 134, 138, 145 Somnolence, 27, 145 Sorbitol, 110, 145 Spasm, 113, 120, 145 Spasmolytic, 75, 145 Spasticity, 113, 145 Specialist, 99, 146 Species, 116, 125, 126, 133, 134, 142, 146, 149, 150, 151 Spectrum, 12, 50, 146 Sperm, 111, 146 Spinal cord, 38, 113, 116, 117, 133, 135, 136, 138, 142, 143, 146 Spinal Nerve Roots, 142, 144, 146 Sporadic, 135, 146 Stabilization, 18, 42, 51, 146 Stabilizer, 82, 116, 146 Staging, 143, 146 Status Epilepticus, 24, 41, 43, 70, 146 Sterile, 70, 146 Steroids, 120, 146 Stimulus, 125, 130, 143, 146, 148 Stomach, 123, 125, 126, 128, 131, 135, 138, 146 Stress, 41, 116, 126, 135, 143, 146 Stroke, 39, 67, 70, 92, 146 Subacute, 129, 146 Subclinical, 129, 144, 146 Subiculum, 128, 146 Substance P, 133, 144, 147 Sulfur, 131, 133, 147 Superoxide, 6, 147 Superoxide Dismutase, 6, 147 Suppression, 120, 147 Supraspinal, 114, 147 Suspensions, 51, 147 Sympathomimetic, 111, 123, 125, 136, 147 Symptomatic, 11, 20, 110, 147 Symptomatic treatment, 110, 147 Synapsis, 147 Synaptic, 9, 147 Synchrony, 28, 147 Synergistic, 62, 140, 147 Systemic, 88, 114, 122, 123, 125, 129, 130, 142, 147

T Tachycardia, 71, 147 Tardive, 112, 147 Telencephalon, 114, 147 Temporal, 111, 125, 128, 147 Temporal Lobe, 111, 125, 147 Tetrahydrocannabinol, 115, 148 Tetrodotoxin, 70, 148 Thalamic, 6, 148 Thalamus, 6, 122, 131, 148 Therapeutics, 19, 33, 36, 55, 60, 88, 148 Third Ventricle, 148 Threshold, 125, 128, 148 Thrombosis, 141, 146, 148 Tin, 66, 137, 138, 148 Tinnitus, 75, 148, 150 Tolerance, 20, 63, 109, 127, 148 Topical, 77, 128, 148 Toxic, iv, 12, 30, 31, 47, 52, 119, 121, 128, 132, 136, 144, 148, 151 Toxicity, 7, 12, 20, 23, 47, 51, 123, 148 Toxicology, 9, 34, 50, 94, 148 Toxins, 112, 129, 148 Trace element, 117, 148, 149 Transcriptase, 131, 149, 151 Transfection, 114, 149 Transmitter, 109, 113, 123, 130, 136, 149 Transplantation, 118, 149 Trauma, 70, 122, 135, 149 Tremor, 25, 137, 149 Tricyclic, 11, 110, 122, 132, 149 Trigeminal, 20, 61, 149 Trigger zone, 112, 149 Tumor marker, 114, 149 Tyrosine, 123, 149 U Unconscious, 129, 149 Urea, 70, 149 Urethra, 141, 149 Urinary, 12, 56, 149 Urine, 9, 12, 114, 122, 131, 149 V Vaccine, 141, 149 Valproic Acid, 6, 8, 9, 12, 35, 41, 51, 60, 82, 149 Vascular, 124, 129, 130, 136, 150 Vasodilation, 123, 150 Vasodilator, 115, 123, 128, 150 Vein, 130, 136, 150 Ventricle, 111, 120, 128, 148, 150 Ventricular, 120, 147, 150 Venules, 115, 116, 150

Index 161

Verbal Behavior, 41, 150 Vertebrae, 130, 146, 150 Vesicular, 133, 150 Vestibulocochlear Nerve, 148, 150 Vestibulocochlear Nerve Diseases, 148, 150 Veterinary Medicine, 93, 150 Viral, 10, 150, 151 Virulence, 148, 150 Virus, 47, 54, 150 Vitro, 14, 150

Vivo, 12, 13, 150 W Wart, 78, 150 Weight Gain, 32, 82, 151 White blood cell, 112, 132, 151 Withdrawal, 11, 35, 52, 122, 151 X Xenograft, 111, 151 X-ray, 119, 136, 142, 144, 146, 151 Z Zalcitabine, 131, 151

162

Lamotrigine

Index 163

164

Lamotrigine

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