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

NEURONTIN 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 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Neurontin: 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: 0-597-83631-0 1. Neurontin-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 Neurontin. 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 NEURONTIN .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Neurontin ..................................................................................... 4 E-Journals: PubMed Central ......................................................................................................... 8 The National Library of Medicine: PubMed .................................................................................. 8 CHAPTER 2. NUTRITION AND NEURONTIN .................................................................................... 25 Overview...................................................................................................................................... 25 Finding Nutrition Studies on Neurontin .................................................................................... 25 Federal Resources on Nutrition ................................................................................................... 29 Additional Web Resources ........................................................................................................... 30 CHAPTER 3. ALTERNATIVE MEDICINE AND NEURONTIN .............................................................. 33 Overview...................................................................................................................................... 33 National Center for Complementary and Alternative Medicine.................................................. 33 Additional Web Resources ........................................................................................................... 36 General References ....................................................................................................................... 37 CHAPTER 4. CLINICAL TRIALS AND NEURONTIN .......................................................................... 39 Overview...................................................................................................................................... 39 Recent Trials on Neurontin ......................................................................................................... 39 Keeping Current on Clinical Trials ............................................................................................. 43 CHAPTER 5. PATENTS ON NEURONTIN........................................................................................... 45 Overview...................................................................................................................................... 45 Patents on Neurontin .................................................................................................................. 45 Patent Applications on Neurontin............................................................................................... 52 Keeping Current .......................................................................................................................... 58 CHAPTER 6. BOOKS ON NEURONTIN .............................................................................................. 59 Overview...................................................................................................................................... 59 The National Library of Medicine Book Index ............................................................................. 59 Chapters on Neurontin ................................................................................................................ 60 CHAPTER 7. PERIODICALS AND NEWS ON NEURONTIN ................................................................ 63 Overview...................................................................................................................................... 63 News Services and Press Releases................................................................................................ 63 Newsletter Articles ...................................................................................................................... 66 Academic Periodicals covering Neurontin................................................................................... 67 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 71 Overview...................................................................................................................................... 71 NIH Guidelines............................................................................................................................ 71 NIH Databases............................................................................................................................. 73 Other Commercial Databases....................................................................................................... 75 APPENDIX B. PATIENT RESOURCES ................................................................................................. 77 Overview...................................................................................................................................... 77 Patient Guideline Sources............................................................................................................ 77 Finding Associations.................................................................................................................... 80 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 83 Overview...................................................................................................................................... 83 Preparation................................................................................................................................... 83 Finding a Local Medical Library.................................................................................................. 83 Medical Libraries in the U.S. and Canada ................................................................................... 83 ONLINE GLOSSARIES.................................................................................................................. 89

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Contents Online Dictionary Directories ..................................................................................................... 89

NEURONTIN DICTIONARY........................................................................................................ 91 INDEX .............................................................................................................................................. 109

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

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

Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients with Diabetes Mellitus: A Randomized Controlled Trial Source: JAMA. Journal of the American Medical Association. 280(21): 1831-1836. December 2, 1998. Summary: Pain is the most disturbing symptom of diabetic peripheral neuropathy (disease or deterioration of the nerves), a problem in up to 45 percent of patients with diabetes mellitus. Pain due to diabetic neuropathy affects the feet and ankles most often and, to a lesser extent, lower extremities above the knees and upper extremities. This article reports on a study undertaken to evaluate the effect of gabapentin (Neurontin) monotherapy on the pain associated with diabetic peripheral neuropathy. The randomized, double blind, placebo controlled, 8 week trial included 165 patients enrolled at outpatient clinics at 20 sites. The patients all had a 1 to 5 year history of pain

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attributed to diabetic neuropathy and a minimum pain score on an evaluation instrument (Short Form McGill Pain Questionnaire visual analog scale). Patients (n = 81) received gabapentin or placebo (n = 81); of these, 70 patients receiving gabapentin completed the study and 60 patients receiving placebo completed the study. By intent to treat analysis, gabapentin treated patients' mean daily pain score at the study end point was significantly lower compared with the placebo treated patients' end point score. All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life. Adverse events experienced significantly more frequently in the gabapentin group were dizziness and somnolence (sleepiness). The authors conclude that gabapentin monotherapy appears to be effective for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life. 4 figures. 3 tables. 42 references.

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

Project Title: GABAPENTIN DETOXIFICATION

AND

LORAZEPAM

IN

OUTPATIENT

Principal Investigator & Institution: Malcolm, Robert J.; Professor; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 10-DEC-1995; Project End 30-NOV-2005 Summary: The alcohol withdrawal syndrome (AWS) has been treated for nearly forty years with the remarkably safe and effective benzodiazepines (BZs). In the outpatient treatment of AWS, interactions with alcohol and the abuse liability of BZs invite comparisons with agents that do not share these susceptibilities. In our original Alcohol Research Center component comparing Lorazepam (LZ) to Carbamazepine (CBZ), the latter was significantly more effective in suppressing the acoustic startle response, and anxiety and depressive symptoms during treatment. In the immediate seven-day post treatment, LZ subjects showed higher levels of multiple dimensions of AWS symptoms, 2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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including higher withdrawal scores, poor sleep, and greater subjective discomfort than CBZ. CBZ, useful in research has limited clinical applications because of its widespread interactions and uncommon but serious toxicities. In the present application, we propose a double-blind controlled trial of gabapentin (GBP, 80) vs. LZ (N=80) in treatment seeking outpatients experiencing AWS. Multiple domains of AWS will be evaluated during a five-day outpatient treatment interval and a seven-day post treatment phase. Serial measures include electrophysiologic tests of eye blink acoustic startle response, aggregate withdrawal symptoms as evaluated by the CIWA-Ar, subjective assessments of sleep, global discomfort, anxiety, depression, and need for additional medications. Side effects and safety will be compared. GMP, a unique anticonvulsant, is not a controlled substance, soon will be generic, has benign side effects, has no interactions with other drugs, and has limited interactions with alcohol. Side effects and safety will be compared. GBP, a unique anticonvulsant, is not a controlled substance, soon will be generic, has benign side effects, has no interactions with other drugs, and has limited interactions with alcohol. Should GBP be superior to LZ for the treatment of AWS, it could revise the way AWS is managed in outpatients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAPENTIN AS AN ADJUNCT TO NALTREXONE FOR ALCOHOLISM Principal Investigator & Institution: Anton, Raymond F.; Professor of Psychiatry; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-AUG-2007 Summary: (provided by applicant): Experience gained conducting numerous clinical trials with alcoholics has provided the infrastructure and knowledge for us to address novel treatments in a scientifically vigorous manner. In particular, we have found naltrexone to be efficacious when combined with cognitive behavioral therapy (CBT) and are currently investigating its efficacy when combined with either CBT or motivational enhancement therapy. In both studies, comprising over 250 individuals, most relapse occurs during early treatment (during the first six weeks) during which individuals complain of sleep difficulty, irritability and nervousness. These symptoms are indicative of brain dysregulation and may be related to "protracted alcohol withdrawal". Gabapentin, a safe and effective FDA approved antiseizure compound used in millions of individuals worldwide, can reduce glutamate and increase GABA neurotransmission in the brain. This unique pharmacology is well suited to the treatment of alcohol withdrawal and could normalize the brain dysregulation seen during the early abstinence period. A number of pre-clinical and clinical studies at our Center have indicated that it can reduce alcohol withdrawal symptoms, reduce drinking in dependent animals, and is safe to use in the clinic. We purpose a randomized double blind clinical trial, to evaluate the adjunctive use of gabapentin with naltrexone for the treatment of alcohol dependent individuals using a three group (placebo alone, placebo plus naltrexone, gabapentin plus naltrexone) design. Gabapentin or placebo will be added to naltrexone for the first six weeks of treatment (the time of greatest relapse and of potential 'protracted withdrawal" symptoms). Naltrexone and/or placebo treatment will last 16 weeks and all subjects will receive Combined Behavioral Intervention as developed for the COMBINE study (in which we are participating). It is predicted that alcoholics receiving naltrexone and adjunctive gabapentin will have less relapse than those treated with naltrexone alone. Measures of mood, sleep, irritability, and anxiety will be compared between treatment groups. Evaluations occur during treatment and 12

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weeks and 24 weeks post-treatment. This evaluation of a novel treatment will allow us to better understand combined pharmacotherapy and develop a new paradigm for medications development for alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAPENTIN THERAPY FOR THE PRURITUS OF CHOLESTASIS Principal Investigator & Institution: Bergasa, Nora V.; Medicine; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-JAN-2003 Summary: The etiology of the pruritus of cholestasis is unknown and its treatment unsatisfactory. The pruritus of cholestasis has a negative impact on the quality of life of patients and can be so severe that it can be an indication for liver transplantation, ever in the face of good hepatic function. Accordingly, the provision of satisfactory treatment for this symptom is needed. Pruritus is a nociceptive stimulus that elicits the reflect act of scratching. Because the perception of nociception can be altered by drugs that mediate antinociception, this type of drugs may be of value in the treatment of pruritus. Recent data from animal and clinical studies suggest that gabapentin mediates antinociception/analgesia. The specific aim of this study is to compare the effect of gabapentin to that of placebo on the pruritus of cholestasis. Adult patients with pruritus secondary to liver disease will be studied, in a single blind, randomized, placebo controlled trial. Because pruritus is a perception, it cannot be objectively quantitated. In contrast, the behavioral manifestation of the pruritus of cholestasis, scratching activity, can be objectively quantitated. The primary end point of this study is scratching activity. Scratching activity will be measured by a stem designed specifically to record this behavior. The potential outcome of this study is the identification of an effective form of therapy for the pruritus of cholestasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GABAPENTIN TREATMENT OF ALCOHOL DEPENDENCE Principal Investigator & Institution: Mason, Barbara J.; Associate Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): Gabapentin is a novel anticonvulsant drug that appears to act on both GABA and glutamate systems to reduce CNS excitability characteristic of early abstinence from alcohol. Clinical reports and controlled trials support the efficacy and safety of gabapentin treatment of depression, anxiety, insomnia and alcohol withdrawal. Acamprosate, another glutamate modulating drug, has been found to increase abstinence in controlled trials of alcohol dependence. Thus, a medication that is functionally similar to acamprosate, with efficacy for alcohol withdrawal and the negative affect and disturbances in sleep that are often associated with relapse, is of interest as a potential relapse-prevention medication in alcohol dependence. The primary aim of this study is to evaluate the safety and efficacy of gabapentin for prolonging abstinence and reducing drinking in recently abstinent outpatients with alcohol dependence. A 12-week, double-blind, placebo-controlled, dose-ranging study will be conducted with random assignment to gabapentin 900 mg/d, 1800 mg/d or placebo. Subjects will be 150 outpatients with alcohol dependence. The 3 pharmacological treatment conditions will be administered in conjunction with manual-guided behavioral counseling that incorporates strategies to increase motivation, abstinence, and medication compliance. Counseling and research

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assessments will occur weekly throughout the 12-week treatment phase. Post-treatment assessments will occur at Weeks 13, 24 and 36. It is hypothesized that administration of gabapentin will result in significantly: 1.) Greater rate of cumulative abstinence duration, 2.) Longer latency to first drink, and 3.) Less alcohol consumption on study than placebo, and will show a linear dose effect. Baseline measures of mood and sleep will be examined as potential predictors of treatment outcome. Results will provide key information about the efficacy and safety of gabapentin for relapse prevention during early abstinence in outpatients with alcohol dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAPENTIN VS ESTROGEN FOR THE TREATMENT OF HOT FLUSHES Principal Investigator & Institution: Reddy, Sireesha; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Hot flashes and other climacteric symptoms affect 75% of postmenopausal women in the US and are associated with higher rates of depression and sleep disturbance. Although hormone replacement therapy (HRT) is highly effective in reducing hot flashes, there is concern that HRT is associated with an increased risk of thrombo-embolic events, breast cancer and ovarian cancer. In addition, it is poorly tolerated in clinical practice, with about 30% of women discontinuing therapy after a mean of 4.5 months. Many other women have a contraindication to HRT, such as a history of an estrogen-sensitive tumor, liver dysfunction, or a hypercoagulable state. Safe, effective, and well-tolerated alternative therapies for hot flashes are needed. Gabapentin is a gamma-aminobutyric acid (GABA)-analog approved in 1994 for the treatment of seizures. Since then, it has been shown that gabapentin is efficacious for numerous off-label indications such as neuropathic pain, anxiety, bipolar disorder, and migraine headaches. The investigators have reported that gabapentin is associated with a reduction in the frequency of hot flashes in an uncontrolled series of postmenopausal women who were taking gabapentin for other indications. The investigators also report here preliminary data from a randomized, placebo-controlled trial showing that lowdose gabapentin was associated with a greater reduction in hot flash frequency than placebo after 12 weeks of treatment. However, it is not known whether the efficacy of gabapentin in the treatment of hot flashes and other menopausal symptoms is comparable to that of estrogen, the gold standard. A randomized trial of gabapentin, estrogen and placebo is needed to inform clinicians as to whether gabapentin is an effective alternative to estrogen. The first major aim of this proposal is to assess the screening and recruitment of menopausal women into a randomized trial of gabapentin, estrogen and placebo in the treatment of climacteric symptoms. The second major aim is to obtain preliminary estimates of the frequency and severity of climacteric symptoms among women receiving gabapentin, estrogen and placebo. Pilot data from these two aims will permit estimates of sample-size requirements for a full-scale randomized trial, and of the overall feasibility and cost of such a trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Gabapentin induced cholestasis. by Richardson CE. 2002 Sep 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126306

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Neurontin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Neurontin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “Neurontin” (hyperlinks lead to article summaries): •

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A case of cutaneous leukocytoclastic vasculitis associated with gabapentin. Author(s): Poon DY, Law NM. Source: Singapore Med J. 2003 January; 44(1): 42-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762564&dopt=Abstract

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A postmarketing surveillance study of gabapentin as add-on therapy for 3,100 patients in England. Author(s): Wilton LV, Shakir S. Source: Epilepsia. 2002 September; 43(9): 983-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199723&dopt=Abstract

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A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Author(s): Dirks J, Fredensborg BB, Christensen D, Fomsgaard JS, Flyger H, Dahl JB. Source: Anesthesiology. 2002 September; 97(3): 560-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218520&dopt=Abstract

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Anorgasmia and withdrawal syndrome in a woman taking gabapentin. Author(s): Drabkin R, Calhoun L. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 March; 48(2): 125-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655912&dopt=Abstract

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AUStralian study of titration to effect profile of safety (AUS-STEPS): high-dose gabapentin (neurontin) in partial seizures. Author(s): Beran R, Berkovic S, Black A, Danta G, Dunne J, Frasca J, Grainger K, Kilpatrick C, McKenzie R, McLaughlin D, Schapel G, Somerville E. Source: Epilepsia. 2001 October; 42(10): 1335-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737169&dopt=Abstract

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Case reports - reversal of sensory deficit associated with pain relief after treatment with gabapentin. Author(s): Chong MS, Smith TE, Hanna M. Source: Pain. 2002 April; 96(3): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973006&dopt=Abstract

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Cellular and molecular action of the putative GABA-mimetic, gabapentin. Author(s): Maneuf YP, Gonzalez MI, Sutton KS, Chung FZ, Pinnock RD, Lee K. Source: Cellular and Molecular Life Sciences : Cmls. 2003 April; 60(4): 742-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785720&dopt=Abstract

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Central post-stroke pain syndrome: yet another use for gabapentin? Author(s): Chen B, Stitik TP, Foye PM, Nadler SF, DeLisa JA. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 September; 81(9): 718-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172525&dopt=Abstract

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Characterization of gabapentin overdose using a poison center case series. Author(s): Klein-Schwartz W, Shepherd JG, Gorman S, Dahl B. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645962&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839368&dopt=Abstract

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Comment on Rice ASC, Maton S, the Postherpetic Neuralgia Study Group (UK), gabapentin in postherpetic neuralgia: a randomized, double blind, placebo-controlled study. Author(s): Gehling M, Tryba M. Source: Pain. 2002 April; 96(3): 410-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973022&dopt=Abstract

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Comment on Rice ASC, Maton S, the Postherpetic Neuralgia Study Group (UK), gabapentin in postherpetic neuralgia: a randomized, double blind, placebo-controlled study. Author(s): Bowsher D. Source: Pain. 2002 April; 96(3): 409-10; Author Reply 411-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973021&dopt=Abstract

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Comment on: Serpell et al., gabapentin in neuropathic pain syndromes: a randomised double-blind, placebo controlled trial (Pain 2002; 99: 557-66). Author(s): McCleane GJ. Source: Pain. 2003 May; 103(1-2): 227; Author Reply 228. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749981&dopt=Abstract

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Determination of gabapentin in plasma by liquid chromatography with fluorescence detection after solid-phase extraction with a C18 column. Author(s): Gauthier D, Gupta R. Source: Clinical Chemistry. 2002 December; 48(12): 2259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446488&dopt=Abstract

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Dosing to efficacy with neurontin: the STEPS trial. Study of Titration to Effect Profile of Safety. Author(s): Morrell MJ. Source: Epilepsia. 1999; 40 Suppl 6: S23-6; Discussion S73-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530679&dopt=Abstract

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Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Author(s): Guttuso T Jr, Roscoe J, Griggs J. Source: Lancet. 2003 May 17; 361(9370): 1703-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767738&dopt=Abstract

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Effect of gabapentin on the anticonvulsant activity of antiepileptic drugs against electroconvulsions in mice: an isobolographic analysis. Author(s): Borowicz KK, Swiader M, Luszczki J, Czuczwar SJ. Source: Epilepsia. 2002 September; 43(9): 956-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199720&dopt=Abstract

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Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity? Author(s): Perugi G, Toni C, Frare F, Ruffolo G, Moretti L, Torti C, Akiskal HS. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 584-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454558&dopt=Abstract

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Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers. Author(s): Salinsky MC, Binder LM, Oken BS, Storzbach D, Aron CR, Dodrill CB. Source: Epilepsia. 2002 May; 43(5): 482-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027908&dopt=Abstract

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Flumazenil and dialysis for gabapentin-induced coma. Author(s): Butler TC, Rosen RM, Wallace AL, Amsden GW. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503937&dopt=Abstract

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Gabapentin -- a promising treatment in glossodynia. Author(s): Meiss F, Boerner D, Marsch WC, Fischer M. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 525-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372102&dopt=Abstract

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Gabapentin (neuronetin) in the treatment of SUNCT syndrome. Author(s): Porta-Etessam J, Martinez-Salio A, Berbel A, Benito-Leon J. Source: Cephalalgia : an International Journal of Headache. 2002 April; 22(3): 249; Author Reply 249-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047467&dopt=Abstract

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Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a doubleblind, placebo-controlled study. The International Gabapentin Study Group. Author(s): Anhut H, Ashman P, Feuerstein TJ, Sauermann W, Saunders M, Schmidt B. Source: Epilepsia. 1994 July-August; 35(4): 795-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8082624&dopt=Abstract

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Gabapentin (NEURONTIN)--a novel anticonvulsant. Author(s): Murdoch LA. Source: Axone. 1994 December; 16(2): 56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7727298&dopt=Abstract

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Gabapentin (Neurontin, Parke-Davis). Author(s): Fisher K, McPherson ML. Source: Am J Hosp Palliat Care. 1997 November-December; 14(6): 311-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392729&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391470&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879525&dopt=Abstract

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Gabapentin and posttraumatic stress disorder. Author(s): Malek-Ahmadi P. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 664-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708942&dopt=Abstract

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Gabapentin and PTSD. Author(s): Berigan TR. Source: The Journal of Clinical Psychiatry. 2002 August; 63(8): 744. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197459&dopt=Abstract

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Gabapentin and vigabatrin increase GABA in the human neocortical slice. Author(s): Errante LD, Williamson A, Spencer DD, Petroff OA. Source: Epilepsy Research. 2002 May; 49(3): 203-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076841&dopt=Abstract

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Gabapentin attenuates superior oblique myokymia. Author(s): Tomsak RL, Kosmorsky GS, Leigh RJ. Source: American Journal of Ophthalmology. 2002 May; 133(5): 721-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992881&dopt=Abstract

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Gabapentin augmentation therapy in bipolar depression. Author(s): Wang PW, Santosa C, Schumacher M, Winsberg ME, Strong C, Ketter TA. Source: Bipolar Disorders. 2002 October; 4(5): 296-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479661&dopt=Abstract

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Gabapentin dosing for neuropathic pain: evidence from randomized, placebocontrolled clinical trials. Author(s): Backonja M, Glanzman RL. Source: Clinical Therapeutics. 2003 January; 25(1): 81-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637113&dopt=Abstract

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Gabapentin dosing in the treatment of epilepsy. Author(s): McLean MJ, Gidal BE. Source: Clinical Therapeutics. 2003 May; 25(5): 1382-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867216&dopt=Abstract

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Gabapentin effect on neuropathic pain compared among patients with spinal cord injury and different durations of symptoms. Author(s): Ahn SH, Park HW, Lee BS, Moon HW, Jang SH, Sakong J, Bae JH. Source: Spine. 2003 February 15; 28(4): 341-6; Discussion 346-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590206&dopt=Abstract

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Gabapentin for coeliac plexus pain. Author(s): Pelham A, Lee MA, Regnard CB. Source: Palliative Medicine. 2002 July; 16(4): 355-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132549&dopt=Abstract

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Gabapentin for hot flashes in prostate cancer. Author(s): Jeffery SM, Pepe JJ, Popovich LM, Vitagliano G. Source: The Annals of Pharmacotherapy. 2002 March; 36(3): 433-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895055&dopt=Abstract

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Gabapentin for neuropathic pain following spinal cord injury. Author(s): To TP, Lim TC, Hill ST, Frauman AG, Cooper N, Kirsa SW, Brown DJ. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 2002 June; 40(6): 282-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037709&dopt=Abstract

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Gabapentin for relief of neuropathic pain related to anticancer treatment: a preliminary study. Author(s): Bosnjak S, Jelic S, Susnjar S, Luki V. Source: Journal of Chemotherapy (Florence, Italy). 2002 April; 14(2): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017380&dopt=Abstract

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Gabapentin for the management of hot flushes: a case series. Author(s): Albertazzi P, Bottazzi M, Purdie DW. Source: Menopause (New York, N.Y.). 2003 May-June; 10(3): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792292&dopt=Abstract

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Gabapentin for the treatment of ethanol withdrawal. Author(s): Voris J, Smith NL, Rao SM, Thorne DL, Flowers QJ. Source: Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse. 2003 June; 24(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766380&dopt=Abstract

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Gabapentin for the treatment of familial erythromelalgia pain. Author(s): Pandey CK, Singh N, Singh PK. Source: J Assoc Physicians India. 2002 August; 50: 1094. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421046&dopt=Abstract

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Gabapentin for the treatment of pain in guillain-barre syndrome: a double-blinded, placebo-controlled, crossover study. Author(s): Pandey CK, Bose N, Garg G, Singh N, Baronia A, Agarwal A, Singh PK, Singh U. Source: Anesthesia and Analgesia. 2002 December; 95(6): 1719-23, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456446&dopt=Abstract

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Gabapentin for the treatment of tremor. Author(s): Faulkner MA, Bertoni JM, Lenz TL. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 282-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549962&dopt=Abstract

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Gabapentin in complicated school refusal. Author(s): Durkin JP 2nd. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 June; 41(6): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049438&dopt=Abstract

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Gabapentin in geriatric mania. Author(s): Sethi MA, Mehta R, Devanand DP. Source: Journal of Geriatric Psychiatry and Neurology. 2003 June; 16(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807075&dopt=Abstract

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Gabapentin in late-onset poststroke seizures. Author(s): Alvarez-Sabin J, Montaner J, Padro L, Molina CA, Rovira R, Codina A, Quintana M. Source: Neurology. 2002 December 24; 59(12): 1991-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499501&dopt=Abstract

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Gabapentin in migraine prophylaxis: is it effective and well tolerated? Author(s): Schoonman GG, Wiendels NJ, Ferrari MD. Source: Headache. 2002 March; 42(3): 235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903552&dopt=Abstract

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Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebocontrolled trial. Author(s): Serpell MG; Neuropathic pain study group. Source: Pain. 2002 October; 99(3): 557-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406532&dopt=Abstract

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Gabapentin in painful ophthalmoplegia. Author(s): Mercadante S. Source: Journal of Pain and Symptom Management. 2002 September; 24(3): 288-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458108&dopt=Abstract

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Gabapentin in postamputation phantom limb pain: a randomized, double-blind, placebo-controlled, cross-over study. Author(s): Bone M, Critchley P, Buggy DJ. Source: Regional Anesthesia and Pain Medicine. 2002 September-October; 27(5): 481-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373695&dopt=Abstract

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Gabapentin in the treatment of neuropathic pain after spinal cord injury: a prospective, randomized, double-blind, crossover trial. Author(s): Tai Q, Kirshblum S, Chen B, Millis S, Johnston M, DeLisa JA. Source: J Spinal Cord Med. 2002 Summer; 25(2): 100-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137213&dopt=Abstract

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Gabapentin in the treatment of SUNCT syndrome. Author(s): Porta-Etessam J, Benito-Leon J, Martinez-Salio A, Berbel A. Source: Headache. 2002 June; 42(6): 523-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167142&dopt=Abstract

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Gabapentin increases slow-wave sleep in normal adults. Author(s): Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, Mascha E, Dinner D, Morris HH. Source: Epilepsia. 2002 December; 43(12): 1493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460250&dopt=Abstract

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Gabapentin induced cholestasis. Author(s): Richardson CE, Williams DW, Kingham JG. Source: Bmj (Clinical Research Ed.). 2002 September 21; 325(7365): 635. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242176&dopt=Abstract

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Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Author(s): Dirks J, Petersen KL, Rowbotham MC, Dahl JB. Source: Anesthesiology. 2002 July; 97(1): 102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131110&dopt=Abstract

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Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. Author(s): Kalra S, Cashman NR, Caramanos Z, Genge A, Arnold DL. Source: Ajnr. American Journal of Neuroradiology. 2003 March; 24(3): 476-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637300&dopt=Abstract

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Gabapentin toxicity requiring intubation in a patient receiving long-term hemodialysis. Author(s): Jones H, Aguila E, Farber HW. Source: Annals of Internal Medicine. 2002 July 2; 137(1): 74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093261&dopt=Abstract

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Gabapentin treatment of glossopharyngeal neuralgia: a follow-up of four years of a single case. Author(s): Moretti R, Torre P, Antonello RM, Bava A, Cazzato G. Source: European Journal of Pain (London, England). 2002; 6(5): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160515&dopt=Abstract

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Gabapentin treatment of impulsive-aggressive behaviour. Author(s): Biancosino B, Facchi A, Marmai L, Grassi L. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 June; 47(5): 483-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085684&dopt=Abstract

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Gabapentin treatment of multiple piloleiomyoma-related pain. Author(s): Alam M, Rabinowitz AD, Engler DE. Source: Journal of the American Academy of Dermatology. 2002 February; 46(2 Suppl Case Reports): S27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807464&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199724&dopt=Abstract

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Gabapentin withdrawal presenting as status epilepticus. Author(s): Barrueto F Jr, Green J, Howland MA, Hoffman RS, Nelson LS. Source: Journal of Toxicology. Clinical Toxicology. 2002; 40(7): 925-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507063&dopt=Abstract

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Gabapentin. Author(s): Rosenquist RW. Source: J Am Acad Orthop Surg. 2002 May-June; 10(3): 153-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041936&dopt=Abstract

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Gabapentin. Pfizer. Author(s): Wheeler G. Source: Curr Opin Investig Drugs. 2002 March; 3(3): 470-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054099&dopt=Abstract

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Gabapentin: pharmacology and its use in pain management. Author(s): Rose MA, Kam PC. Source: Anaesthesia. 2002 May; 57(5): 451-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966555&dopt=Abstract

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Gabapentin: resistant neuropathic pain and malignancy. Author(s): Ross JR, Waight C, Riley J, Broadley K. Source: Palliative Medicine. 2001 July; 15(4): 348-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054154&dopt=Abstract

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Gabapentin: the first preemptive anti-hyperalgesic for opioid withdrawal hyperalgesia? Author(s): Gustorff B, Kozek-Langenecker S, Kress HG. Source: Anesthesiology. 2003 June; 98(6): 1520-1; Author Reply 1521-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766674&dopt=Abstract

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Gabapentin-induced anorgasmia in women. Author(s): Grant AC, Oh H. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1247. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091218&dopt=Abstract

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Gabapentin-induced bullous pemphigoid. Author(s): Zachariae CO. Source: Acta Dermato-Venereologica. 2002; 82(5): 396-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430752&dopt=Abstract

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Gabapentin-induced paradoxical exacerbation of psychosis in a patient with schizophrenia. Author(s): Jablonowski K, Margolese HC, Chouinard G. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 December; 47(10): 975-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553139&dopt=Abstract

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High-performance liquid chromatographic method for the determination of gabapentin in human plasma. Author(s): Zhu Z, Neirinck L. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 November 5; 779(2): 307-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361744&dopt=Abstract

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Hyperhidrosis in pediatric spinal cord injury: a case report and gabapentin therapy. Author(s): Adams BB, Vargus-Adams JN, Franz DN, Kinnett DG. Source: Journal of the American Academy of Dermatology. 2002 March; 46(3): 444-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862186&dopt=Abstract

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Improvement of acquired pendular nystagmus by gabapentin: case report. Author(s): Fabre K, Smet-Dieleman H, Zeyen T. Source: Bull Soc Belge Ophtalmol. 2001; (282): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455139&dopt=Abstract

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Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex. Author(s): Fink K, Dooley DJ, Meder WP, Suman-Chauhan N, Duffy S, Clusmann H, Gothert M. Source: Neuropharmacology. 2002 February; 42(2): 229-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804619&dopt=Abstract

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Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. Author(s): Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI, Myers RR. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 December; 303(3): 1199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438544&dopt=Abstract

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Is gabapentin a “Broad-spectrum” analgesic? Author(s): Gilron I. Source: Anesthesiology. 2002 September; 97(3): 537-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218517&dopt=Abstract

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Long-term use of gabapentin for treatment of pain after traumatic spinal cord injury. Author(s): Putzke JD, Richards JS, Kezar L, Hicken BL, Ness TJ. Source: The Clinical Journal of Pain. 2002 March-April; 18(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882775&dopt=Abstract

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Management of restless legs syndrome with gabapentin (Neurontin) Author(s): Mellick GA, Mellick LB. Source: Sleep. 1996 April; 19(3): 224-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723380&dopt=Abstract

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Massive gabapentin and presumptive quetiapine overdose. Author(s): Spiller HA, Dunaway MD, Cutino L. Source: Vet Hum Toxicol. 2002 August; 44(4): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136976&dopt=Abstract

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Mode of action of gabapentin in chronic neuropathic pain syndromes. A short review about its cellular mechanisms in nociceptive neurotransmission. Author(s): Surges R, Feuerstein TJ. Source: Arzneimittel-Forschung. 2002; 52(8): 583-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236044&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839834&dopt=Abstract

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Neurontin--1 year on. London October 1994. Author(s): Betts T. Source: Seizure : the Journal of the British Epilepsy Association. 1995 March; 4(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7788103&dopt=Abstract

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Oral gabapentin (neurontin) treatment of refractory genitourinary tract pain. Author(s): Sasaki K, Smith CP, Chuang YC, Lee JY, Kim JC, Chancellor MB. Source: Tech Urol. 2001 March; 7(1): 47-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272678&dopt=Abstract

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Outcome evaluation of gabapentin as add-on therapy for partial seizures. “NEON” Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological Practice. Author(s): Bruni J. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1998 May; 25(2): 134-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9604135&dopt=Abstract

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Pilot evaluation of gabapentin for treating hot flashes. Author(s): Loprinzi L, Barton DL, Sloan JA, Zahasky KM, Smith de AR, Pruthi S, Novotny PJ, Perez EA, Christensen BJ. Source: Mayo Clinic Proceedings. 2002 November; 77(11): 1159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440550&dopt=Abstract

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Plasma gabapentin concentrations in children with epilepsy: influence of age, relationship with dosage, and preliminary observations on correlation with clinical response. Author(s): Gatti G, Ferrari AR, Guerrini R, Bonanni P, Bonomi I, Perucca E. Source: Therapeutic Drug Monitoring. 2003 February; 25(1): 54-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548145&dopt=Abstract

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Procedure for the monitoring of gabapentin with 2,4,6-trinitrobenzene sulfonic acid derivatization followed by HPLC with ultraviolet detection. Author(s): Juenke JM, Brown PI, McMillin GA, Urry FM. Source: Clinical Chemistry. 2003 July; 49(7): 1198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816924&dopt=Abstract

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Re: Lasso-de-la-Vega et al. gabapentin as a probable cause of hepatotoxicity and eosinophilia. Author(s): Hauben M. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2156-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190207&dopt=Abstract

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Strictly unilateral headache reminiscent of hemicrania continua resistant to indomethacin but responsive to gabapentin. Author(s): Mariano Da Silva H, Alcantara MC, Bordini CA, Speciali JG. Source: Cephalalgia : an International Journal of Headache. 2002 June; 22(5): 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110117&dopt=Abstract

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SUNCT responsive to gabapentin. Author(s): Hunt CH, Dodick DW, Bosch EP. Source: Headache. 2002 June; 42(6): 525-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167143&dopt=Abstract

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SUNCT syndrome responsive to gabapentin (Neurontin). Author(s): Graff-Radford SB. Source: Cephalalgia : an International Journal of Headache. 2000 June; 20(5): 515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037748&dopt=Abstract

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The absorption of gabapentin following high dose escalation. Author(s): Berry DJ, Beran RG, Plunkeft MJ, Clarke LA, Hung WT. Source: Seizure : the Journal of the British Epilepsy Association. 2003 January; 12(1): 2836. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495646&dopt=Abstract

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The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. Author(s): Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. Source: Anesthesia and Analgesia. 2002 October; 95(4): 985-91, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351281&dopt=Abstract

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The anticonvulsant gabapentin (neurontin) does not act through gammaaminobutyric acid-B receptors. Author(s): Jensen AA, Mosbacher J, Elg S, Lingenhoehl K, Lohmann T, Johansen TN, Abrahamsen B, Mattsson JP, Lehmann A, Bettler B, Brauner-Osborne H. Source: Molecular Pharmacology. 2002 June; 61(6): 1377-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021399&dopt=Abstract

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The use of gabapentin for the treatment of postherpetic neuralgia. Author(s): Singh D, Kennedy DH. Source: Clinical Therapeutics. 2003 March; 25(3): 852-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852705&dopt=Abstract

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Three drug reviews: one reformulated and one new antifungal agent and optimal dosing of the anticonvulsant gabapentin. Author(s): Walson PD. Source: Clinical Therapeutics. 2003 May; 25(5): 1293-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867213&dopt=Abstract

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Treatment of alcohol withdrawal with gabapentin. Author(s): Bozikas V, Petrikis P, Gamvrula K, Savvidou I, Karavatos A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 January; 26(1): 197-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853112&dopt=Abstract

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Treatment of post-herpetic pain in myasthenia gravis: exacerbation of weakness due to gabapentin. Author(s): Scheschonka A, Beuche W. Source: Pain. 2003 July; 104(1-2): 423-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855353&dopt=Abstract

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Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Author(s): Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Source: Neurology. 2002 November 26; 59(10): 1573-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451200&dopt=Abstract

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

Finding Nutrition Studies on Neurontin 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 “Neurontin” (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.

26 Neurontin

The following information is typical of that found when using the “Full IBIDS Database” to search for “Neurontin” (or a synonym): •

A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor. Author(s): Department of Neurology, Sant Pau Hospital, Autonomous University of Barcelona, Spain. Source: Gironell, A Kulisevsky, J Barbanoj, M Lopez Villegas, D Hernandez, G Pascual Sedano, B Arch-Neurol. 1999 April; 56(4): 475-80 0003-9942

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A summary of mechanistic hypotheses of gabapentin pharmacology. Author(s): Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105, USA. Source: Taylor, C P Gee, N S Su, T Z Kocsis, J D Welty, D F Brown, J P Dooley, D J Boden, P Singh, L Epilepsy-Res. 1998 February; 29(3): 233-49 0920-1211

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AUStralian study of titration to effect profile of safety (AUS-STEPS): high-dose gabapentin (neurontin) in partial seizures. Author(s): Strategic Health Evaluators, Chatswood, Australia. Source: Beran, R Berkovic, S Black, A Danta, G Dunne, J Frasca, J Grainger, K Kilpatrick, C McKenzie, R McLaughlin, D Schapel, G Somerville, E Epilepsia. 2001 October; 42(10): 1335-9 0013-9580

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Characterization of the effects of gabapentin and 3-isobutyl-gamma-aminobutyric acid on substance P-induced thermal hyperalgesia. Author(s): Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA. Source: Partridge, B J Chaplan, S R Sakamoto, E Yaksh, T L Anesthesiology. 1998 January; 88(1): 196-205 0003-3022

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Disposition of gabapentin (neurontin) in mice, rats, dogs, and monkeys. Author(s): Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA. Source: Radulovic, L L Turck, D von Hodenberg, A Vollmer, K O McNally, W P DeHart, P D Hanson, B J Bockbrader, H N Chang, T Drug-Metab-Dispos. 1995 April; 23(4): 441-8 0090-9556

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Dosing to efficacy with neurontin: the STEPS trial. Study of Titration to Effect Profile of Safety. Author(s): Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York, USA. Source: Morrell, M J Epilepsia. 1999; 40 Suppl 6S23-6; discussion S73-4 0013-9580

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Effect of gabapentin (Neurontin) [corrected] on mood and well-being in patients with epilepsy. Author(s): CNS Clinical Research and Development, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI, USA. Source: Dimond, K R Pande, A C Lamoreaux, L Pierce, M W ProgNeuropsychopharmacol-Biol-Psychiatry. 1996 April; 20(3): 407-17 0278-5846

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FDA approved new drug bulletin. Gabapentin (neurontin). Source: Anonymous RN. 1994 July; 57(7): 39-40 0033-7021

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Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a doubleblind, placebo-controlled study. The International Gabapentin Study Group. Author(s): Parke-Davis Pharmaceutical Research, Freiburg, Germany.

Nutrition 27

Source: Anhut, H Ashman, P Feuerstein, T J Sauermann, W Saunders, M Schmidt, B Epilepsia. 1994 Jul-August; 35(4): 795-801 0013-9580 •

Gabapentin (NEURONTIN)--a novel anticonvulsant. Source: Murdoch, L A Axone. 1994 December; 16(2): 56 0834-7824

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Gabapentin (Neurontin, Parke-Davis). Author(s): University of Maryland School of Pharmacy/Hospice Pharmacia, Baltimore, USA. Source: Fisher, K McPherson, M L Am-J-Hosp-Palliat-Care. 1997 Nov-December; 14(6): 311-2 1049-9091

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Gabapentin actions on N-methyl-D-aspartate receptor channels are protein kinase Cdependent. Author(s): Marine Biomedical Institute, University of Texas Medical Branch, Galveston, TX 77555-1069, USA. Source: Gu, Y Huang, L Y Pain. 2001 July; 93(1): 85-92 0304-3959

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Gabapentin as add-on therapy for refractory partial epilepsy: results of five placebocontrolled trials. Author(s): Parke-Davis Pharmaceutical Research, Division of the Warner-Lambert Company, Ann Arbor 48105. Source: Leiderman, D B Epilepsia. 1994; 35 Suppl 5S74-6 0013-9580

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Gabapentin in generalized seizures. Author(s): Department of Medical and Surgical Neurology, Walton Hospital, Liverpool, UK. Source: Chadwick, D Leiderman, D B Sauermann, W Alexander, J Garofalo, E EpilepsyRes. 1996 November; 25(3): 191-7 0920-1211

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Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Author(s): Department of Biology, Pfizer Global R&D, Cambridge Laboratories, Cambridge, CB2 2QB. [email protected] Source: Sutton, K G Martin, D J Pinnock, R D Lee, K Scott, R H Br-J-Pharmacol. 2002 January; 135(1): 257-65 0007-1188

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Gabapentin is not a GABAB receptor agonist. Author(s): Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Essex, CM19 5AW, Harlow, UK. Source: Lanneau, C Green, A Hirst, W D Wise, A Brown, J T Donnier, E Charles, K J Wood, M Davies, C H Pangalos, M N Neuropharmacology. 2001 December; 41(8): 96575 0028-3908

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Gabapentin, ineffective in normal rats, markedly reduces C-fibre evoked responses after inflammation. Author(s): Department of Pharmacology, University College London, UK. Source: Stanfa, L C Singh, L Williams, R G Dickenson, A H Neuroreport. 1997 February 10; 8(3): 587-90 0959-4965

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Gabapentin. CI 945, GOE 3450, Neurontin. Source: Anonymous Drugs-R-D. 1999 December; 2(6): 385-9 1174-5886

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Gabapentin: discussion. Author(s): Department of Neurology, University of Pittsburgh, School of Medicine, Pennsylvania 15261. Source: Fromm, G H Epilepsia. 1994; 35 Suppl 5S77-80 0013-9580

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Gabapentin--a new antiepileptic drug. Source: Anonymous Drug-Ther-Bull. 1994 April 21; 32(4): 29-30 0012-6543

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Gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Author(s): Merck Frosst Center for Therapeutic Research, Kirkland, Canada. [email protected] Source: Ng, G Y Bertrand, S Sullivan, R Ethier, N Wang, J Yergey, J Belley, M Trimble, L Bateman, K Alder, L Smith, A McKernan, R Metters, K O'Neill, G P Lacaille, J C Hebert, T E Mol-Pharmacol. 2001 January; 59(1): 144-52 0026-895X

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Identification of novel ligands for the gabapentin binding site on the alpha2delta subunit of a calcium channel and their evaluation as anticonvulsant agents. Author(s): Parke Davis Neuroscience Research Centre, Cambridge University Forvie Site, Robinson Way, Cambridge CB2 2QB, U.K. Source: Bryans, J S Davies, N Gee, N S Dissanayake, V U Ratcliffe, G S Horwell, D C Kneen, C O Morrell, A I Oles, R J O'Toole, J C Perkins, G M Singh, L Suman Chauhan, N O'Neill, J A J-Med-Chem. 1998 May 21; 41(11): 1838-45 0022-2623

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Neurontin--1 year on. London October 1994. Author(s): Epilepsy Liaison Service and Seizure Clinic, Birmingham University, UK. Source: Betts, T Seizure. 1995 March; 4(1): 1-4 1059-1311

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Oral gabapentin (neurontin) treatment of refractory genitourinary tract pain. Author(s): Department of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USA. Source: Sasaki, K Smith, C P Chuang, Y C Lee, J Y Kim, J C Chancellor, M B Tech-Urol. 2001 March; 7(1): 47-9 1079-3259

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Outcome evaluation of gabapentin as add-on therapy for partial seizures. “NEON” Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological Practice. Author(s): Wellesly Hospital, Toronto, Ontario, Canada. Source: Bruni, J Can-J-Neurol-Sci. 1998 May; 25(2): 134-40 0317-1671

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Preferential action of gabapentin and pregabalin at P/Q-type voltage-sensitive calcium channels: inhibition of K+-evoked [3H]-norepinephrine release from rat neocortical slices. Author(s): Department of CNS Pharmacology, Pfizer Global Research & Development, Ann Arbor, Michigan 48105, USA. [email protected] Source: Dooley, D J Donovan, C M Meder, W P Whetzel, S Z Synapse. 2002 September 1; 45(3): 171-90 0887-4476

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Reflex sympathetic dystrophy treated with gabapentin. Author(s): American Pain Specialists, Inc., Elyria, OH 44035, USA. Source: Mellick, G A Mellick, L B Arch-Phys-Med-Rehabil. 1997 January; 78(1): 98-105 0003-9993

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Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. Author(s): Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA. Source: Haig, G M Bockbrader, H N Wesche, D L Boellner, S W Ouellet, D Brown, R R Randinitis, E J Posvar, E L J-Clin-Pharmacol. 2001 May; 41(5): 507-14 0091-2700

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SUNCT syndrome responsive to gabapentin (Neurontin). Author(s): The Pain Center of Cedars-Sinai Medical Center and UCLA School of Dentistry, Los Angeles, CA, USA. Source: Graff Radford, S B Cephalalgia. 2000 June; 20(5): 515-7 0333-1024

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The anticonvulsant gabapentin (neurontin) does not act through gammaaminobutyric acid-B receptors. Author(s): NeuroScience PharmaBiotec Research Centre, Department of Medicinal Chemistry, the Royal Danish School of Pharmacy, Copenhagen, Denmark. Source: Jensen, Anders A Mosbacher, Johannes Elg, Susanne Lingenhoehl, Kurt Lohmann, Tania Johansen, Tommy N Abrahamsen, Bjarke Mattsson, January P Lehmann, Anders Bettler, Bernhard Brauner Osborne, Hans Mol-Pharmacol. 2002 June; 61(6): 1377-84 0026-895X

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The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine. Author(s): Department of Biology, Parke-Davis Neuroscience Research Center, Cambridge, UK. Source: Singh, L Field, M J Ferris, P Hunter, J C Oles, R J Williams, R G Woodruff, G N Psychopharmacology-(Berl). 1996 September; 127(1): 1-9 0033-3158

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The long-term safety and efficacy of gabapentin (Neurontin) as add-on therapy in drug-resistant partial epilepsy. The US Gabapentin Study Group. Source: Anonymous Epilepsy-Res. 1994 May; 18(1): 67-73 0920-1211

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

The following is a specific Web list relating to Neurontin; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation (some Web sites are subscription based): •

Vitamins Folic Acid Source: Healthnotes, Inc. www.healthnotes.com Vitamin A Source: Healthnotes, Inc. www.healthnotes.com Vitamin B12 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc. www.healthnotes.com Vitamin D Source: Healthnotes, Inc. www.healthnotes.com Vitamin K Source: Healthnotes, Inc. www.healthnotes.com

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Minerals Biotin Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Healthnotes, Inc. www.healthnotes.com

Nutrition 31

Gabapentin Source: Healthnotes, Inc. www.healthnotes.com L-Carnitine Source: Healthnotes, Inc. www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND NEURONTIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Neurontin. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Neurontin and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Neurontin” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to Neurontin: •

A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin. Author(s): Ness TJ, San Pedro EC, Richards JS, Kezar L, Liu HG, Mountz JM. Source: Pain. 1998 November; 78(2): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839825&dopt=Abstract

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Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes. Author(s): Greenberg DB, Jonasch E, Gadd MA, Ryan BF, Everett JR, Sober AJ, Mihm MA, Tanabe KK, Ott M, Haluska FG. Source: Cancer. 2000 July 15; 89(2): 356-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918166&dopt=Abstract

•

Advances in the medical treatment of epilepsy. Author(s): Bazil CW, Pedley TA.

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Source: Annual Review of Medicine. 1998; 49: 135-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509255&dopt=Abstract •

An East-West approach to the management of central post-stroke pain. Author(s): Yen HL, Chan W. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766358&dopt=Abstract

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Anti-allodynic action of the tormentic acid, a triterpene isolated from plant, against neuropathic and inflammatory persistent pain in mice. Author(s): Bortalanza LB, Ferreira J, Hess SC, Delle Monache F, Yunes RA, Calixto JB. Source: European Journal of Pharmacology. 2002 October 25; 453(2-3): 203-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398905&dopt=Abstract

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Antiepileptic drug therapy. Author(s): Podell M. Source: Clin Tech Small Anim Pract. 1998 August; 13(3): 185-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9775509&dopt=Abstract

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Antimyoclonic effect of gabapentin in a posthypoxic animal model of myoclonus. Author(s): Kanthasamy AG, Vu TQ, Yun RJ, Truong DD. Source: European Journal of Pharmacology. 1996 February 22; 297(3): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8666053&dopt=Abstract

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Determination of gabapentin in plasma by high-performance liquid chromatography. Author(s): Forrest G, Sills GJ, Leach JP, Brodie MJ. Source: Journal of Chromatography. B, Biomedical Applications. 1996 June 7; 681(2): 421-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8811458&dopt=Abstract

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Felbamate, gabapentin and topiramate as adjuvant antiepileptic drugs in experimental models of epilepsy. Author(s): Czuczwar SJ, Przesmycki K. Source: Pol J Pharmacol. 2001 January-February; 53(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785915&dopt=Abstract

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Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain. Author(s): Caraceni A, Zecca E, Martini C, De Conno F. Source: Journal of Pain and Symptom Management. 1999 June; 17(6): 441-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10388250&dopt=Abstract

Alternative Medicine 35

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Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. Author(s): De Sarro G, Spagnolo C, Gareri P, Gallelli L, De Sarro A. Source: European Journal of Pharmacology. 1998 May 22; 349(2-3): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9671096&dopt=Abstract

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Gabapentin, an adjuvant treatment for neuropathic pain in a cancer hospital. Author(s): Chandler A, Williams JE. Source: Journal of Pain and Symptom Management. 2000 August; 20(2): 82-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032490&dopt=Abstract

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Management of spasticity, pain, and paroxysmal phenomena in multiple sclerosis. Author(s): Schapiro RT. Source: Curr Neurol Neurosci Rep. 2001 May; 1(3): 299-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898533&dopt=Abstract

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Management of surgically hypogonadal patients unable to take sex hormone replacement therapy. Author(s): Nieman LK. Source: Endocrinology and Metabolism Clinics of North America. 2003 June; 32(2): 32536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800534&dopt=Abstract

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Myalgias and arthralgias associated with paclitaxel. Author(s): Garrison JA, McCune JS, Livingston RB, Linden HM, Gralow JR, Ellis GK, West HL. Source: Oncology (Huntingt). 2003 February; 17(2): 271-7; Discussion 281-2, 286-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632867&dopt=Abstract

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Novel treatments for bipolar disorder. Author(s): Bowden CL. Source: Expert Opinion on Investigational Drugs. 2001 April; 10(4): 661-71. Review. Erratum In: Expert Opin Investig Drugs 2001 July; 10(7): Following 1205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281816&dopt=Abstract

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R3 nociceptive reflex in multiple sclerosis patients with paroxysmal symptoms treated with gabapentin. Author(s): D'Aleo G, Rifici C, Sessa E, Di Bella P, Bramanti P. Source: Funct Neurol. 2000 October-December; 15(4): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11213523&dopt=Abstract

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Science reporters hear wide range of recent data at 12th annual conference. Author(s): Skolnick AA, Manack L. Source: Jama : the Journal of the American Medical Association. 1993 November 24; 270(20): 2413-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8230606&dopt=Abstract

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Treatment of postherpetic neuralgia. Author(s): Menke JJ, Heins JR. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 1999 March-April; 39(2): 217-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10079653&dopt=Abstract

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Use of gabapentin to treat taxane-induced myalgias. Author(s): van Deventer H, Bernard S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 January; 17(1): 434-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458265&dopt=Abstract

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Vincristine-induced allodynia in the rat. Author(s): Nozaki-Taguchi N, Chaplan SR, Higuera ES, Ajakwe RC, Yaksh TL. Source: Pain. 2001 July; 93(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406340&dopt=Abstract

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What nonhormonal therapies are effective for postmenopausal vasomotor symptoms? Author(s): Brewer D, Nashelsky J. Source: The Journal of Family Practice. 2003 April; 52(4): 324-5, 329; Discussion 329. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681094&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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

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

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

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

The following is a specific Web list relating to Neurontin; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation (some Web sites are subscription based): •

Herbs and Supplements Anticonvulsants Source: Healthnotes, Inc. www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. CLINICAL TRIALS AND NEURONTIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Neurontin.

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

Comparing Gabapentin and Lorazepam for Treating Alcohol Withdrawal Condition(s): Alcoholism Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study will evaluate a safe and useful medication for outpatient detoxification that is as effective as benzodiazepines in the short-term, and more effective in the protracted withdrawal period. gabapentin (Neurontin) will be compared to a standard benzodiazepine, lorazepam (Ativan), for its effectiveness in treating alcohol withdrawal. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011297

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Gabapentin For the Control of Hot Flashes in Women With Breast Cancer Condition(s): Anxiety Disorder; Breast Cancer; Depression; Hot Flashes; Quality of Life Study Status: This study is currently recruiting patients. Sponsor(s): James P. Wilmot Cancer Center; National Cancer Institute (NCI)

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: RATIONALE: gabapentin may be effective for the control of hot flashes. It is not yet known if gabapentin is effective in treating hot flashes. PURPOSE: Randomized clinical trial to study the effectiveness of gabapentin in controlling hot flashes in women who have breast cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022074 •

Gabapentin in Fibromyalgia Trial (GIFT) Condition(s): Fibromyalgia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will assess the safety and effectiveness of the drug gabapentin in reducing pain associated with primary fibromyalgia. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057278

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Gabapentin in Treating Hot Flashes in Patients With Prostate Cancer Condition(s): stage I prostate cancer; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer; Hot Flashes Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: gabapentin may be effective in relieving hot flashes in men who have prostate cancer. It is not yet known which regimen of gabapentin is most effective in treating hot flashes. PURPOSE: Randomized phase III trial to compare different regimens of gabapentin in treating men who have prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028574

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Gabapentin in Treating Peripheral Neuropathy in Cancer Patients Undergoing Chemotherapy Condition(s): neurotoxicity; Pain; Quality of Life Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: gabapentin may be effective in relieving pain and other symptoms of peripheral neuropathy. It is not yet known if gabapentin is effective in treating peripheral neuropathy in cancer patients undergoing chemotherapy. PURPOSE: Randomized phase III trial to determine the effectiveness of gabapentin in

Clinical Trials 41

treating pain and other symptoms of peripheral neuropathy in cancer patients undergoing chemotherapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027963 •

Gabapentin to treat itch in patients with liver disease Condition(s): Liver Disease; Cholestasis; Cirrhosis; Pruritus; Itching Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: In this study, the effect of the medication gabapentin to treat itching secondary to liver disease is being studied. There are some funds to cover travel expenses for patients who are not from New York. gabapentin is approved to treat seizures in human beings. In this study, patients with liver disease who meet inclusion criteria are admitted to the research hospital of the New York Presbyterian Hospital to record scratching behavior by the use of a machine designed for that purpose. Blood work will be obtained. After completion of recording, patients are assigned by chance to receive active medication or placebo (a capsule that does not contain active medication). The patients will come to the outpatient office of the research hospital 2 weeks into the study for an interview and blood work. After 4 weeks, patients are readmitted to the hospital to record scratching behavior. After data are collected, the code is broken, if patient had been on inactive drug, active drug will be supplied as per protocol for 4 weeks. Blood work will be obtained. If patient had been randomized to active medication, the study will provide one week supply of drug. After that, the referring physician, with whom the study was previously discussed, could prescribe the medication as it is available. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058890

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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 no longer recruiting patients. 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

42 Neurontin

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 •

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: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015106

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New Drugs in the Treatment of Mood Disorders Condition(s): Anxiety Disorder; Mood Disorder; Psychotic Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This clinical study compares the effectiveness of two anticonvulsants Lamotrigine (Lamictal) Monotherapy and gabapentin (Neurontin) in patients with treatment resistant affective disorders. We initially have found that the response rate to lamotrigine (51%) exceeded that of gabapentin (28%) or placebo (21%). In this study the placebo phase has been dropped so that we examine possible clinical and biological factors predictors of response. The drugs will be given in a randomized order for six weeks each and you will not know when you are on a given one. There will be a 2-4 week "washout" period between treatments. If you respond well to one of these treatments, a longer open continuation period will be offered at the end of this study. This would involve one or both drugs in combination. A variety of rating scales and brain imaging procedures will also be offered before and during each drug evaluation. Both lamotrigine and gabapentin are generally well tolerated. A serious potentially life threatening rash occurs in about 1/500 patients treated with lamotrigine, however. Common side effects are rash, dizziness, unsteadiness, double vision, blurred vision, nausea, vomiting, insomnia, sedation, and headache. These side effects are usually mild, and resolve with continued time on the drug or a decrease in dosage. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00001482

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 “Neurontin” (or synonyms). 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 5. PATENTS ON NEURONTIN 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 “Neurontin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Neurontin, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Neurontin By performing a patent search focusing on Neurontin, 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 Neurontin: •

Combination of riluzole and of gabapentin and its use as a medicament Inventor(s): Bohme; Andrees (Paris, FR), Henderson; Christopher (Cassis, FR) Assignee(s): Aventis Pharma S.A. (Antony Cedex, FR) Patent Number: 6,350,768 Date filed: November 22, 2000 Abstract: The present invention relates to the combination of riluzole and of gabapentin or one of their pharmaceutically acceptable salts and its use as a medicament which is useful in particular for the prevention and/or treatment of motoneuron diseases. Excerpt(s): The present invention relates to the combination of riluzole and of gabapentin or one of their pharmaceutically acceptable salts and its use as a medicament which is useful in particular for the prevention and/or treatment of motoneuron diseases.... Motoneuron diseases include in particular amyotrophic lateral sclerosis, progressive spinal amyotrophy, infantile spinal amyotrophy and primary lateral sclerosis. They are caused by a progressive loss of motoneurons in the spinal cord.... Amyotrophic lateral sclerosis (ALS), also known by the name of CHARCOT's disease and LOU GEHRIG's disease, was described for the first time by CHARCOT in 1865. It is the most important motoneuron disease. ALS is a fatal disease resulting from degeneration of the motoneurons. The disease is accompanied by progressive paralysis, leading to the loss of motor and respiratory functions and then to death within a period of two to eight years after the appearance of the first symptoms. Web site: http://www.delphion.com/details?pn=US06350768__

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Gabapentin mohohydrate and a process for producing the same Inventor(s): Greenman; Barbara J. (Door, MI), Butler; Donald E. (Holland, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 4,960,931 Date filed: October 6, 1989 Abstract: A novel crystalline form of gabapentin and a novel processes for the small and large scale preparations of the anticonvulsant compound in a highly pure state is disclosed. This novel hydrate is produced by a cost effective process which provides an additional purification stage. Excerpt(s): All examples of the syntheses end in an isocyanate or urethane that can easily be converted into the desired (1-aminomethyl)-1-cyclohexaneacetic acid by acidic hydrolysis (preferred) to give an acid or basic hydrolysis to give a basic salt or followed by acidification to give an acid salt.... The present invention provides crystalline gabapentin monohydrate, a novel, highly pure substance of reasonable bulk density suitable for formulation in the desired forms such as capsules or tablets. Its properties are those sought in a pharmaceutical product. The present invention provides both a small scale and a large scale method for producing gabapentin monohydrate. This form, the hydrate of the free amino acid, has the advantage of being less expensive to produce than the known form of gabapentin. The process has the advantage of having barely

Patents 47

detectable residues of solvents such as 2-propanol. No detectable methanol or ethanol residuals remain. Also, the process for producing the hydrate provides an extra purification step even if one goes on to produce the anhydrous material. The hydrate saves 12-13% of the total yield of gabapentin by eliminating the losses confronted in the final recrystallization. The hydrate also saves the cost of solvents, man hours, and utilities used in the final recrystallization The product is a very pretty crystal which is stable at ambient temperatures (20-25.degree. C.).... The instant invention is a novel form of gabapentin, crystalline gabapentin monohydrate with the following unique X-ray diffraction properties. Web site: http://www.delphion.com/details?pn=US04960931__ •

Gabapentin monohydrate and a process for producing the same Inventor(s): Greenman; Barbara J. (Door, MI), Butler; Donald E. (Holland, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 4,894,476 Date filed: May 2, 1988 Abstract: A novel crystalline form of gabapentin and a novel processes for the small and large scale preparations of the anticonvulsant compound in a highly pure state is disclosed. This novel hydrate is produced by a cost effective process which provides an additional purification stage. Excerpt(s): All examples of the syntheses end in an isocyanate or urethane that can easily be converted into the desired (1-aminomethyl)-1-cyclohexaneacetic acid by acidic hydrolysis (preferred) to give an acid or basic hydrolysis to give a basic salt or followed by acidification to give an acid salt.... The present invention provides crystalline gabapentin monohydrate, a novel, highly pure substance of reasonable bulk density suitable for formulation in the desired forms such as capsules or tablets. Its properties are those sought in a pharmaceutical product. The present invention provides both a small scale and a large scale method for producing gabapentin monohydrate. This form, the hydrate of the free amino acid, has the advantage of being less expensive to produce than the known form of gabapentin. The process has the advantage of having barely detectable residues of solvents such as 2-propanol. No detectable methanol or ethanol residuals remain. Also, the process for producing the hydrate provides an extra purification step even if one goes on to produce the anhydrous material. The hydrate saves 12-13% of the total yield of gabapentin by eliminating the losses confronted in the final recrystallization. The hydrate also saves the cost of solvents, man hours, and utilities used in the final recrystallization. The product is a very pretty crystal which is stable at ambient temperatures (20.degree.-25.degree. C.).... The instant invention is a novel form of gabapentin, crystalline gabapentin monohydrate with the following unique X-ray diffraction properties. Web site: http://www.delphion.com/details?pn=US04894476__

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Pharmaceutical tablet formulation containing gabapentin with improved physical and chemical characteristics and method of making the same Inventor(s): Vilkov; Zalman (Dingman's Ferry, PA) Assignee(s): Purepac Pharmaceutical Co. (Elizabeth, NJ) Patent Number: 6,465,012 Date filed: June 6, 2001 Abstract: A pharmaceutical formulation form with improved physical and chemical characteristics, comprising gabapentin in tablet form for oral administration. The tablet form can be prepared by spray-coating gabapentin with a binder solution and compressing the spray-coated gabapentin into non-friable, stable tablets. This method is particularly useful for tablet formulations that require large doses of active drug. Excerpt(s): This invention is generally directed to pharmaceutical formulations with improved physical and chemical characteristics, comprising gabapentin in tablet form for oral administration. The tablet form can be prepared by spray-coating gabapentin with a binder solution and compressing the spray-coated gabapentin into non-friable, stable tablets. This invention is also generally directed to a method of producing pharmaceutical formulations in tablet form which contain large doses of active drug by spray-coating the active drug with a binder solution and compressing the spray-coated active drug into tablets.... Prior art methods for improving the compression characteristics of pharmaceutical formulations involve introducing additional excipients, such as microcrystalline cellulose, as compression aids to prevent fracturing of granules and tablets. However, the inclusion of additional excipients can be expensive and time consuming, can effect the stability of the active drug agent, and can increase the size of the tablet.... Other methods for improving the compression characteristics of pharmaceutical formulations include dissolving the active drug in a binder solution to form a drug solution, spray drying the drug solution to form a powder and then compressing the powder into a tablet. This method, however, is inefficient because it requires a large amount of binder solution. Moreover, dissolving the active drug in a solution can cause stability problems, polymorph conversion, and changes in the crystalline structure of the drug. Web site: http://www.delphion.com/details?pn=US06465012__

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Preparation of gabapentin Inventor(s): Singer; Claude (Kfar Saba, IL), Pesachovich; Michael (Givat Shmuel, IL), Pilarski; Gideon (Holon, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (Petah Tiqva, IL) Patent Number: 6,255,526 Date filed: June 22, 1999 Abstract: There is disclosed a method of converting gabapenting hydrochloride substantially free of inorganic salts to gabapenting form II. The method comprises the steps of: (1) obtaining gabapentin hydrochloride that is substantially free of inorganic salts; (2) mixing a solution of the gabapenting hydrochloride with an additional amine in a first solvent so as to obtain a precipitate comprising gabapenting; and then (3) recovering gabapentin form II from the precipitate. The precipitated gabapentin is a novel polymorphic form of gabapentin possessing a crystalline structure characterized

Patents 49

by novel sets of peaks in the powder X-ray diffraction pattern and in the FTIR spectra. This newly disclosed polymorph of gabapentin is characterized herein as gabapentin form III. The recovery step may comprise, for example, one of two alternative methods, slurrying the gabapentin form II in methanol, and then filtering the suspension to obtain gabapentin form II, or solubilizing the gabapentin form III in methanol with heating by reflux, and then cooling the solution to obtain gabapentin form II by crystallization. Excerpt(s): This invention relates to a new process for converting gabapentin hydrochloride salt to gabapentin via a novel polymorphic form of gabapentin.... Gabapentin is used in the treatment of cerebral diseases such as epilepsy. The literature describes many ways of preparing gabapentin from a variety of starting materials. U.S. Pat. No. 4,024,175 describes at least three methods of preparing gabapentin from cyclohexyl-1,1-diacetic acid. Each of these methods results in the formation of gabapentin hydrochloride salt, which may be converted to 1-(aminomethyl)-1cyclohexaneacetic acid by treatment with a basic ion exchanger and then crystallized from a solvent such as ethanol/ether.... U.S. Pat. No. 4,894,476 specifically discloses an improved method for converting the hydrochloride salt into the free amino acid. This involves pouring a deionized water solution of the salt over an ion exchange column, eluting with deionized water, producing a slurry from the eluate, adding an alcohol to the slurry, centrifuging and drying the slurry to obtain the free amino acid. Web site: http://www.delphion.com/details?pn=US06255526__ •

Process for producing gabapentin or pharmaceutical grade Inventor(s): Onrubia Miguel; Ma del Carmen (Barcelona, ES), Bosch Llado; Jordi (Girona, ES), Pagans Lista; Eugenia (Celra, ES) Assignee(s): Medichem, S.A. (Barcelona, ES) Patent Number: 6,528,682 Date filed: October 18, 2001 Abstract: The invention describes a process for the preparation of pharmaceutical grade gabapentin, consisting of neutralizing an alcoholic solution of gabapentin hydrochloride with basic ion exchange resins and thereafter directly isolating the gabapentin, without requiring either the formation or the isolation of intermediates other than the pharmaceutical grade product. Excerpt(s): The present invention relates to a process for the preparation of gabapentin suitable for pharmaceutical use by neutralization of alcoholic solutions of gabapentin hydrochloride with basic ion exchange resins.... The said compound has a therapeutical activity for convulsive type cerebral disorders, such as epilepsy, hypokinesia, including fainting, and other brain trauma and, in general, it is deemed to produce an improvement of the cerebral functions.... Gabapentin and several processes for the preparation thereof are described in Spanish patent ES-A-443 723, corresponding to U.S. Pat. No. 4,024,175, Example 1 of which describes the preparation of the free amino acid from the hydrochloride thereof, by treatment of an aqueous solution thereof with a basic ion exchanger, evaporation of the solvent and subsequent crystallization from a mixture of ethanol/ether. This process, which is only outlined without details in the said patents, has drawbacks for the industrial application thereof derived from having to evaporate large amounts of water, with the high energy consumption required thereby, and involving the use of a solvent such as ether, which is extremely dangerous and hard to handle on an industrial scale.

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Web site: http://www.delphion.com/details?pn=US06528682__ •

Process for the preparation of gabapentin Inventor(s): Caraccia; Nicola (Novi Ligure, IT), Giordani; Cristiana (Novi Ligure, IT), Tenconi; Franco (Novi Ligure, IT) Assignee(s): Bioindustria Laboratorio Italiano Medicinali S.p.A. (Novi Ligure, IT) Patent Number: 6,576,790 Date filed: February 25, 2002 Abstract: A process for the preparation of gabapentin starting from gabapentin hydrochloride, which comprises the following steps: preparing a gabapentin hydrochloride aqueous solution; adjusting the pH of the solution to or about to gabapentin isoelectric point by addition of a basic compound comprising a monovalent anion; diafiltering the solution through a membrane highly selective for organic compounds with molecular weight higher than 150 and poorly selective for inorganic monovalent ions, to separate the solution into an aqueous permeate containing chloride ions and a retentate containing unsalified gabapentin substantially free from chloride ions; concentrating the retentate by increasing the pressure exerted on the membrane to obtain a concentration of unsalified gabapentin in the retentate not lower than 5%; evaporating the retentate under reduced pressure and at T.degree.<35.degree. precipitating gabapentin by addition of an alcohol. Excerpt(s): The present invention generally relates to the pharmaceutical chemistry field.... Gabapentin is an active ingredient used in the treatment of various cerebral diseases, such as epilepsy, hypokinesia, cranial traumas and the like and is the object of U.S. Pat. No. 4,024,175 and U.S. Pat. No. 4,087,544.... A number of processes for preparation of gabapentin are reported in literature; U.S. Pat. No. 4,024,175, for example, discloses some preparation methods starting from cyclohexyl-1,1-diacetic acid. Web site: http://www.delphion.com/details?pn=US06576790__

•

Stable gabapentin containing more than 20 ppm of chlorine ion Inventor(s): Schwartz; Edward (Rehovot, IL), Pilarski; Gideon (Holon, IL), Singer; Claude (Kfar Saba, IL), Pesachovich; Michael (Givat Shmuel, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (Petah Tiqva, IL) Patent Number: 6,531,509 Date filed: June 15, 2001 Abstract: Pharmaceutical compositions containing substantially pure and stable gabapentin are disclosed wherein gabapentin contains an anion of a mineral acid, such as chloride, in amounts greater than 20 ppm. Excerpt(s): The present invention relates to a pharmaceutical composition containing therapeutically effective amount of gabapentin and its derivatives in combination with effective carriers. More particularly, the present invention relates to a composition and a process for manufacturing pure and stable gabapentin having greater than 20 ppm of chloride ion.... Gabapentin is used for treating cerebral diseases such as epilepsy, faintness attacks, hypokinesis and cranial traumas. U.S. Pat. No. 4,024,175 to Satzinger et al., incorporated herein by reference, discloses that gabapentin of formula (I) shows

Patents 51

hypothermal and, in some cases, narcosis-potentiating or sedating properties as well as protective effect against cardiozole cramp in animals. Finally, gabapentin has been found especially useful in treating geriatric patients. As such, there has been a need for producing pure and stable gabapentin.... forms during the preparation and storage of gabapentin. According to Augart, because the lactam has a higher toxicity than gabapentin, its presence in gabapentin should be limited if not eliminated. To combat lactam formation and provide product stability, Augart stresses the importance of (i) starting with gabapentin raw material that contains 0.5% or less of corresponding lactam, (ii) not allowing the anion of a mineral acid in the composition to exceed 20 ppm, and (iii) using a specifically selected adjuvant that is not adverse to gabapentin stability. Web site: http://www.delphion.com/details?pn=US06531509__ •

Stereoselective processes for the preparation of gabapentin analogues Inventor(s): Morrell; Andrew Ian (Kent, GB), Bryans; Justin Stephen (Balsham, GB) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,465,689 Date filed: December 8, 1999 Abstract: This invention is novel processes for the stereoselective preparation of gabapentin analogues. Excerpt(s): The instant invention provides a stereoselective synthesis for the ringsubstituted analogs of gabapentin and to gabapentin itself. The advantages of the instant syntheses are: control of stereochemistry and no resolution is required at the end of the synthesis.... The invention encompasses a novel synthetic route for the preparation of substituted gabapentin analogues. The route enables the synthesis of certain single stereoisomers of individual alkylated gabapentin derivatives with a high degree of stereochemical purity.... The invention is outlined in the general route shown below. The first step involves conversion of a substituted cyclohexanone to an (.alpha.,.beta.unsaturated ester via use of a trialkylphosphonoacetate or an (alkoxycarbonylmethyl)triphenyl-phosphonium halide and a base, such as sodium hydride, potassium hydride, lithium- or sodium- or potassium-hexamethyldisilazide, butyllithium or potassium t-butoxide in a solvent such as tetrahydrofuran, dimethylformamide, diethylether, or dimethylsulfoxide at a suitable temperature in the range from -78.degree. C. to 100.degree. C. Web site: http://www.delphion.com/details?pn=US06465689__

•

Use of GABA analogs such as Gabapentin in the manufacture of a medicament for treating inflammatory diseases Inventor(s): Westlund High; Karin Nanette (League City, TX), Taylor, Jr. Charles Price (Chelsea, MI), Schrier; Denis (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,329,429 Date filed: October 25, 1999

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Abstract: GABA analogs such as gabapentin and pregabalin are useful to prevent and treat inflammatory diseases. Excerpt(s): This invention relates to a method for treating inflammatory diseases by administering a gamma-aminobutyric acid (GABA) analog.... Inflammatory diseases are characterized by a complex series of histological events, including dilatation of arterioles, capillaries, and venules, with increased permeability and blood flow; exudation of fluids, including plasma proteins; and leukocytic migration into the inflammatory focus. Many forms of inflammation are localized protective responses elicited by injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. The inflammatory response itself is also responsible for pathologic tissue damage. Arthritis is a particularly devastating inflammatory disease, generally affecting older people, and is characterized by the inflammatory lesions being primarily confined to articular joints. The disease is marked by pain, heat, redness, swelling, and tissue destruction. Rheumatoid arthritis is a chronic systemic disease of the joints, marked by inflammatory changes in the synovial tissue and articular structures, and by atrophy and rarefaction of the bones. This form of inflammatory disease generally progresses to deformity and ankylosis.... Numerous anti-inflammatory treatments are known and commonly used. The most common are the nonsteroidal anti-inflammatory agents such as naproxen, diflunisal, mefenamic acid, and ketorolac tromethamine. These agents generally are used to treat short term mild inflammation and pain. More severe inflammatory disease, such as arthritis, are treated with steroidal hormones and glucocorticoids, for example prednisolone, hydrocortisone acetate, and betamethasone sodium phosphate. Web site: http://www.delphion.com/details?pn=US06329429__

Patent Applications on Neurontin 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 Neurontin: •

Anhydrous crystalline forms of gabapentin Inventor(s): Tobias, Brian; (Ann Arbor, MI), Babu, Suresh R. (Canton, MI), Chen, Linna R. (West Linn, OR), Calvitt, Claude Jeffrey; (Saline, MI) Correspondence: MERCHANT & GOULD PC; P.O. BOX 2903; MINNEAPOLIS; MN; 55402-0903; US Patent Application Number: 20030092933 Date filed: September 25, 2002 Abstract: Described are new crystalline anhydrous forms of gabapentin formed from gabapentin monohydrate. The new crystalline forms provide advantages in the manufacture of the therapeutic agent. Excerpt(s): This application claims benefit of application Ser. No. 60/328,375 of Oct. 9, 2001, which application is incorporated herein by reference.... The present invention relates to new anhydrous crystalline forms of gabapentin prepared from gabapentin

10

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

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monohydrate.... It is useful in therapy of certain cerebral disorders such as certain forms of epilepsy, faintness attacks, hypokinesia, and cranial traumas. U.S. Pat. Nos. 4,024,175 and 4,087,544 cover the compound and its uses. They also disclose an acid salt, i.e., gabapentin hydrochloride hydrate in a ratio of 4:4:1 and a sodium salt of gabapentin hydrate at a ratio of 2:1. U.S. Pat. No. 4,894,476 describes gabapentin monohydrate and a process for producing it. These patents are incorporated by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Gabapentin prodrugs and formulations Inventor(s): Chen, Jane; (Davie, FL), Chen, Chih-Ming; (Davie, FL) Correspondence: DAVIDSON, DAVIDSON & KAPPEL, LLC; 485 SEVENTH AVENUE, 14TH FLOOR; NEW YORK; NY; 10018; US Patent Application Number: 20020107208 Date filed: October 23, 2001 Abstract: The present invention relates to novel prodrugs of gabapentin and to pharmaceutical formulations and sustained release formulations containing the prodrugs. Excerpt(s): This application claims priority to provisional application no. 60/242,924 filed Oct. 24, 2001, the disclosure of which is hereby incorporated by reference.... Gabapentin is a cyclohexaneacetic acid derivative that is sold under the trademark NEURONTIN for the treatment of partial seizures in adults with epilepsy. The current administration regimen requires 900 to 1800 mgs/day and given in divided doses of three times per day using 300-400 mg capsules. While the drug is highly effective for its prescribed use, there is a need to develop a version of the drug that is administered in a once-a-day regimen and which provides an equally efficacious pharmaceutical product and improved side effect profile.... Gabapentin is 1-(aminomethyl)cyclohexaneacetic acid. This compound is highly soluble in water and in both basic and acidic conditions. The drug per se is not extensively metabolized in humans and is eliminated via renal excretion essentially unchanged. At the typical dosage range (300-600 mgs T.I.D.) the oral bioavailability is approximately sixty percent. The gabapentin elimination half life is five to seven hours and is unaltered by dose or following multiple dosing. Thus, there is a need for an improved product profile that increases bioavailability and provides for a once a day dosing regimen. U.S. Pat. No. 4,087,544 discloses the compound known as gabapentin and various analogs thereof including, for example, the alkyl esters having an R group in place of the carboxylic acid hydrogen wherein R is selected from an alkyl radical containing up to 8 carbon atoms. Specific alkyl groups disclosed include ethyl, methyl and n-butyl. Pharmaceutical compositions and methods of use are also generically disclosed. There is no teaching of therein or reference to the use of any of these compounds in a sustained release formulation. U.S. Pat. No. 5,955,103 discloses certain dosage forms that may contain various active ingredients including gabapentin but it does not disclose or relate to sustained release dosage forms containing pro-drugs of gabapentin. There is a need to combine the advantages of a prodrug of gabapentin and a sustained release delivery system to provide the slow and efficacious delivery of the pro-drug and ultimately the active metabolite of said prodrug-gabapentin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Methods of treatment using a gastric retained gabapentin dosage Inventor(s): Hou, Sui Yuen Eddie; (Foster City, CA), Berner, Bret; (El Granada, CA), Gusler, Gloria M. (Cupertino, CA) Correspondence: COOLEY GODWARD, LLP; 3000 EL CAMINO REAL; 5 PALO ALTO SQUARE; PALO ALTO; CA; 94306; US Patent Application Number: 20030100611 Date filed: January 22, 2003 Abstract: A method of treatment for epilepsy and other disease states is described, which comprises the delivery of gabapentin in a gastric retained dosage form. Excerpt(s): The present invention relates to the use of gabapentin in a gastric retained dosage form. More specifically, the invention relates to the use of such dosage form to treat epilepsy and other disease states.... Gabapentin (1-(aminomethyl)cyclohexaneacetic acid) is an anti-epileptic drug that is currently available in 100 mg, 300 mg and 400 mg hard shell capsule as well as 600 mg and 800 mg tablet dosage forms, with recommended dosing of 900 mg to 1800 mg total daily dose in three divided dosages. The oral bioavailability is dose-dependent, with approximately 60% bioavailability for a dose in the range of 300-400 mg, but with only 35% bioavailability for a dose of 1600 mg (Bourgeois, Epilepsia 36 (Suppl. 5):S1-S7 (1995); Gram, Epilepsia 37 (Suppl. 6):S12-S16 (1996)). The decrease in bioavailability with dose has been attributed to carrier-mediated absorption (Stewart, et al., Pharmaceutical Research 10(2):276-281 (1993).... In early work with rats, Vollmer, et al., Arzneim-Forsch/Drug Research 36(1, Nr. 5):781-892 (1986) found that the absorption site for gabapentin was the duodenum. The absorption of gabapentin occurs relatively slowly with the peak plasma concentration occurring approximately 2-6 hours after dosing (Bourgeois, supra). The elimination of gabapentin is exclusively through renal pathways (Chadwick; The Lancet 343:89-91 (1994); Vollmer, supra; Thomson, et al., Clin. Pharmacokinet. 23(3):216-230 (1992); and Riva, et al., Clin. Pharmacokinet. 31(6):470-493 (1996)) with reported half-lives of 5-7 hours (Chadwick, supra) and 6-7 hours (Gram, supra). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Pharmaceutical tablet formulation containing gabapentin with improved physical and chemical characteristics and method of making the same Inventor(s): Vilkov, Zalman; (Dingman's Ferry, PA) Correspondence: Robert G. Mukai; BURNS, DOANE, SWECKER & MATHIS, L.L.P. P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030008004 Date filed: August 29, 2002 Abstract: A pharmaceutical formulation form with improved physical and chemical characteristics, comprising gabapentin in tablet form for oral administration. The tablet form can be prepared by spray-coating gabapentin with a binder solution and compressing the spray-coated gabapentin into non-friable, stable tablets. This method is particularly useful for tablet formulations that require large doses of active drug. Excerpt(s): This invention is generally directed to pharmaceutical formulations with improved physical and chemical characteristics, comprising gabapentin in tablet form for oral administration. The tablet form can be prepared by spray-coating gabapentin

Patents 55

with a binder solution and compressing the spray-coated gabapentin into non-friable, stable tablets. This invention is also generally directed to a method of producing pharmaceutical formulations in tablet form which contain large doses of active drug by spray-coating the active drug with a binder solution and compressing the spray-coated active drug into tablets.... Prior art methods for improving the compression characteristics of pharmaceutical formulations involve introducing additional excipients, such as microcrystalline cellulose, as compression aids to prevent fracturing of granules and tablets. However, the inclusion of additional excipients can be expensive and time consuming, can effect the stability of the active drug agent, and can increase the size of the tablet.... Other methods for improving the compression characteristics of pharmaceutical formulations include dissolving the active drug in a binder solution to form a drug solution, spray drying the drug solution to form a powder and then compressing the powder into a tablet. This method, however, is inefficient because it requires a large amount of binder solution. Moreover, dissolving the active drug in a solution can cause stability problems, polymorph conversion, and changes in the crystalline structure of the drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Stable gabapentin compositions Inventor(s): Nicoli, Andrea; (Vicenza, IT), Corcella, Francesco; (Rozzano, IT), Cannata, Vincenzo; (Sasso Marconi, IT) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C. 1940 DUKE STREET; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030119908 Date filed: December 21, 2001 Abstract: Stable compositions containing gabapentin compositions, methods of preparing such compositions, and methods of using such compositions. Excerpt(s): The present invention relates to stable gabapentin compositions. The present invention also relates to methods of preparing these compositions and to methods of using these compositions.... Gabapentin (1-aminomethyl)cyclohexaneacetic acid) is a well-known therapeutic for treating and improving a variety of neurological/cerebral conditions and also improve cerebral functions. Examples of such conditions include epilepsy, faintness attacks, hypokinesia, cranial traumas, as described in, for example, U.S. Pat. No. 4,024,175.... However, these methods are not entirely satisfactory for prodcuing gabapentin of high purity. Accordingly, there remains a need in the art for stable gabapentin compositions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stable gabapentin containing more than 20 ppm of chlorine ion Inventor(s): Singer, Claude; (Kfar Saba, IL), Pilarsky, Gideon; (Holon, IL), Pesachovich, Michael; (Givat Shmuel, IL) Correspondence: KENYON & KENYON; 1500 K STREET, N.W., SUITE 700; WASHINGTON; DC; 20005; US Patent Application Number: 20020061931 Date filed: June 15, 2001 Abstract: Pharmaceutical compositions containing substantially pure and stable gabapentin are disclosed wherein gabapentin contains an anion of a mineral acid, such as chloride, in amounts greater than 20 ppm. Excerpt(s): This invention relates to PCT Application No. WO 98/28255, filed Jul. 2, 1998, also assigned to the assignee of the present invention and incorporated herein by reference; this invention also claims priority to U.S. Provisional Application No. 60/211,967 filed Jun. 16, 2001.... The present invention relates to a pharmaceutical composition containing therapeutically effective amount of gabapentin and its derivatives in combination with effective carriers. More particularly, the present invention relates to a composition and a process for manufacturing pure and stable gabapentin having greater than 20 ppm of chloride ion.... Gabapentin is used for treating cerebral diseases such as epilepsy, faintness attacks, hypokinesis and cranial traumas. U.S. Pat. No. 4,024,175 to Satzinger et al., incorporated herein by reference, discloses that gabapentin of formula (I) shows hypothermal and, in some cases, narcosis-potentiating or sedating properties as well as protective effect against cardiozole cramp in animals. Finally, gabapentin has been found especially useful in treating geriatric patients. As such, there has been a need for producing pure and stable gabapentin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Stable gabapentin having pH within a controlled range Inventor(s): Pesachovich, Michael; (Givat Shmuel, IL), Pilarski, Gideon; (Holon, IL), Singer, Claude; (Kfar Saba, IL), Pesachovich, Michael; (Givat Shmuel, IL), Pilarski, Gideon; (Holon, IL), Singer, Claude; (Kfar Saba, IL) Correspondence: KENYON & KENYON; 1500 K STREET, N.W., SUITE 700; WASHINGTON; DC; 20005; US, KENYON & KENYON; 1500 K STREET, N.W., SUITE 700; WASHINGTON; DC; 20005; US Patent Application Number: 20030055109 Date filed: August 26, 2002 Abstract: A pharmaceutical composition containing substantially pure and stable gabapentin are disclosed wherein gabapentin has a pH of between 6.8 to 7.3. Excerpt(s): This invention relates to PCT Application No. WO 98/28255, filed Jul. 2, 1998, also assigned to the assignee of the present invention and incorporated herein by reference; the present invention also claims priority to U.S. Provisional Application No. 60/211,966, filed Jun. 16, 2000.... This invention relates to PCT Application No. WO 98/28255, filed Jul. 2, 1998, also assigned to the assignee of the present invention and incorporated herein by reference; the present invention also claims priority to U.S. Provisional Application No. 60/211,966, filed Jun. 16, 2000.... The present invention relates to a pharmaceutical composition containing therapeutically effective amount of

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gabapentin and its derivatives in combination with effective carriers. More particularly, the present invention relates to a stable composition and a process for manufacturing pure and stable gabapentin having a pH in the range of 6.8 to 7.3.... The present invention relates to a pharmaceutical composition containing therapeutically effective amount of gabapentin and its derivatives in combination with effective carriers. More particularly, the present invention relates to a stable composition and a process for manufacturing pure and stable gabapentin having a pH in the range of 6.8 to 7.3.... Gabapentin is used for treating cerebral diseases such as epilepsy, faintness attacks, hypokinesis and cranial traumas. U.S. Pat. No. 4,024,175 to Satzinger et al., incorporated herein by reference, discloses that gabapentin of formula (I) shows hypothermal and, in some cases, narcosis-potentiating or sedating properties as well as protective effect against cardiozole cramp in animals. Finally, gabapentin has been found especially useful in treating geriatric patients. As such, there has been a need for producing pure and stable gabapentin.... Gabapentin is used for treating cerebral diseases such as epilepsy, faintness attacks, hypokinesis and cranial traumas. U.S. Pat. No. 4,024,175 to Satzinger et al., incorporated herein by reference, discloses that gabapentin of formula (I) shows hypothermal and, in some cases, narcosis-potentiating or sedating properties as well as protective effect against cardiozole cramp in animals. Finally, gabapentin has been found especially useful in treating geriatric patients. As such, there has been a need for producing pure and stable gabapentin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Stable gabapentin having pH within a controlled range Inventor(s): Pesachovich, Michael; (Givat Shmuel, IL), Pilarski, Gideon; (Holon, IL), Singer, Claude; (Kfar Saba, IL), Pesachovich, Michael; (Givat Shmuel, IL), Pilarski, Gideon; (Holon, IL), Singer, Claude; (Kfar Saba, IL) Correspondence: KENYON & KENYON; 1500 K STREET, N.W., SUITE 700; WASHINGTON; DC; 20005; US, KENYON & KENYON; 1500 K STREET, N.W., SUITE 700; WASHINGTON; DC; 20005; US Patent Application Number: 20030055109 Date filed: August 26, 2002 Abstract: A pharmaceutical composition containing substantially pure and stable gabapentin are disclosed wherein gabapentin has a pH of between 6.8 to 7.3. Excerpt(s): This invention relates to PCT Application No. WO 98/28255, filed Jul. 2, 1998, also assigned to the assignee of the present invention and incorporated herein by reference; the present invention also claims priority to U.S. Provisional Application No. 60/211,966, filed Jun. 16, 2000.... This invention relates to PCT Application No. WO 98/28255, filed Jul. 2, 1998, also assigned to the assignee of the present invention and incorporated herein by reference; the present invention also claims priority to U.S. Provisional Application No. 60/211,966, filed Jun. 16, 2000.... The present invention relates to a pharmaceutical composition containing therapeutically effective amount of gabapentin and its derivatives in combination with effective carriers. More particularly, the present invention relates to a stable composition and a process for manufacturing pure and stable gabapentin having a pH in the range of 6.8 to 7.3.... The present invention relates to a pharmaceutical composition containing therapeutically effective amount of gabapentin and its derivatives in combination with effective carriers. More particularly, the present invention relates to a stable composition and a process for manufacturing pure and stable gabapentin having a pH in the range of 6.8 to 7.3....

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Gabapentin is used for treating cerebral diseases such as epilepsy, faintness attacks, hypokinesis and cranial traumas. U.S. Pat. No. 4,024,175 to Satzinger et al., incorporated herein by reference, discloses that gabapentin of formula (I) shows hypothermal and, in some cases, narcosis-potentiating or sedating properties as well as protective effect against cardiozole cramp in animals. Finally, gabapentin has been found especially useful in treating geriatric patients. As such, there has been a need for producing pure and stable gabapentin.... Gabapentin is used for treating cerebral diseases such as epilepsy, faintness attacks, hypokinesis and cranial traumas. U.S. Pat. No. 4,024,175 to Satzinger et al., incorporated herein by reference, discloses that gabapentin of formula (I) shows hypothermal and, in some cases, narcosis-potentiating or sedating properties as well as protective effect against cardiozole cramp in animals. Finally, gabapentin has been found especially useful in treating geriatric patients. As such, there has been a need for producing pure and stable gabapentin. 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 Neurontin, 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 “Neurontin” (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 Neurontin. You can also use this procedure to view pending patent applications concerning Neurontin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON NEURONTIN Overview This chapter provides bibliographic book references relating to Neurontin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Neurontin include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Neurontin” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

11

New trends in epilepsy management: the role of gabapentin: proceedings of a satellite symposium held during Epilepsy Europe 1992 Author: Chadwick, David.; Year: 1993; London; New York: Royal Society of Medicine Services, 1993; ISBN: 1853151947 http://www.amazon.com/exec/obidos/ASIN/1853151947/icongroupinterna

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Chapters on Neurontin In order to find chapters that specifically relate to Neurontin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Neurontin using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “Neurontin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Neurontin: •

Oral Medications Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 81-112. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on oral medications used to treat IC is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. Oral medications, used alone or in combination with other medications, will improve symptoms in most patients with IC. Patients may still have some symptoms while on oral medications, but they may be improved to the point where they wish to wait before undergoing more invasive therapy. Most of the medications used cause few significant side effects. The author notes that most of the medications discussed in this chapter have been used for many years but for other purposes. Medications and dosages may need to be changed due to side effects or poor responses. The author first discusses medications thought to coat the bladder's surface, including pentosan polysulfate sodium (Elmiron), chondroitin sulfate, and glucosamine. The author then discusses the use of antidepressants (primarily to reduce pain), including amitriptyline (Elavil); selective serotonin reuptake inhibitors (SSRIs); antihistamines, including hydroxyzine (Atarax, Vistaril); cromolyn sodium (Gastrocrom); cimetidine (Tagamet); antiseizure medications, including gabapentin (Neurontin), and carbamazepine (Tegretol); nonsteroidal antiinflammatory drugs (NSAIDs); immunosuppressants, including steroids; muscle relaxants, notably diazepam (Valium); narcotic therapy; urinary anesthetics, including phenazopyridine hydrochloride (Pyridium), atropine sulfate, benzoic acid, hyoscyamine, methenamine, methylene blue, and phenyl salicylate (Urised); anticholinergic therapy; L arginine; calcium channel blockers, including nifedipine (Procardia); and alpha blockers. The author reviews the use of each of these drugs, along with the hypothesis about why they may be of use in IC.

•

Individual Antiepileptic Drugs Source: in Essentials of Clinical Epilepsy. Second Edition. Guberman, A.H. Bruni, J. Woburn, MA, Butterworth-Heinemann, pp. 115-149, 1999.

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Contact: Butterworth-Heinemann Publications, 225 Wildwood Avenue, Woburn, MA 01801-2041. (781) 904-2500. FAX: (781) 904-2620. INTERNET/EMAIL: http://www.bh.com. Summary: Individual Antiepileptic Drugs, a chapter in Essentials of Clinical Epilepsy, describes drugs used in the treatment of epilepsy, including (1) chemical features, (2) mechanism of action, (3) pharmacology, (4) daily dose, (5) efficacy, (6) principal adverse effects, (7) advantages, and (8) disadvantages. These drugs include carbamazepine (Tegretol, Tegretol-XR, Carbatrol, Tegretol CR in Canada), clobazam (Frisium), clonazepam (Klonopin, Rivotril in Canada), ethosuximide (Zarontin), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), oxcarbazepine (Trileptal), phenobarbital, primidone (Mysoline), phenytoin (Dilantin), tiagabine (Gabitril), topiramate (Topamax), valproate (Depakote, Epival in Canada, Depakene Syrup, Depacon IV, Epiject IV in Canada), and vigabatrin (Sabril).

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CHAPTER 7. PERIODICALS AND NEWS ON NEURONTIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Neurontin.

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

Ivax says first to seek ok for Neurontin generic Source: Reuters Industry Breifing Date: September 15, 2003 http://www.reutershealth.com/archive/2003/09/15/business/links/20030915inds018. html

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Court upholds Alpharma's Neurontin exclusivity Source: Reuters Industry Breifing Date: April 28, 2003

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Pfizer in talks on settling Neurontin inquiry -- WSJ Source: Reuters Industry Breifing Date: March 12, 2003

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Alpharma secures 180-day exclusivity period for generic Neurontin capsules Source: Reuters Industry Breifing Date: January 29, 2003

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Pfizer says appeals court upholds Neurontin ruling Source: Reuters Industry Breifing Date: January 16, 2003

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Apotex's generic Neurontin deemed approvable by FDA Source: Reuters Industry Breifing Date: December 09, 2002

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FDA takes issue with model brain used to promote Pfizer's Neurontin Source: Reuters Industry Breifing Date: July 19, 2002

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Pfizer says FDA clears antifungal Vfend, expands Neurontin indications Source: Reuters Industry Breifing Date: May 28, 2002

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Ivax says generic Neurontin approvable by FDA Source: Reuters Industry Breifing Date: May 07, 2002

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Pfizer's Warner-Lambert probed on Neurontin marketing Source: Reuters Medical News Date: March 14, 2002

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FDA grants pediatric indication to Parke-Davis' antiepileptic Neurontin Source: Reuters Industry Breifing Date: October 13, 2000

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Faulding sues Warner-Lambert for right to sell generic Neurontin Source: Reuters Industry Breifing Date: May 05, 2000

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•

Gabapentin may be new option for treatment of essential tremor Source: Reuters Medical News Date: April 22, 1999

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Gabapentin treats nerve pain Source: Reuters Health eLine Date: December 01, 1998 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Neurontin” (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 “Neurontin” (or synonyms). If you know the name of a company that is relevant to Neurontin, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Neurontin” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “Neurontin” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on Neurontin: •

Pharmacological Treatment of Vulvodynia Source: NVA News. 7(3): 1,3-8. Spring 2002. Contact: Available from National Vulvodynia Association. P.O. Box 4491, Silver Spring, MD 20914-4491. (301) 299-0775. Fax (301) 299-3999. Website: www.nva.org. Summary: This newsletter article provides health professionals with information on the pharmacological treatment of vulvodynia. Although the treatment of this disorder has traditionally been considered using the neuropathic pain model, it is unclear whether vulvodynia is actually a neuropathic pain disorder. Vulvodynia has been presumed to be a neuropathic pain disorder because patients usually report a painful vulvar burning sensation and vulvar allodynia. In addition, vulvodynia can sometimes be treated with tricyclic antidepressants, drugs commonly used to treat neuropathic pain conditions. However, these factors do not prove that vulvodynia is a neuropathic pain disorder. The article contends that most cases of vulvodynia, a seemingly localized pain disorder, are not primary neuropathic pain conditions, but rather, a part of a more generalized condition possibly related to fibromyalgia. If this is true, then the best pharmacological treatments for vulvodynia may be different than what was assumed to be the case using the neuropathic pain model of vulvodynia. In addition, the issue of causality of vulvodynia becomes even more complicated because all chronic pain conditions, regardless of whether they begin as true neuropathic pain conditions or not, can induce a central nervous system pathological process known as central sensitization. Therefore, pharmacological treatments that can reverse or prevent the process of central sensitization may be beneficial for both neuropathic and nonneuropathic chronic pain syndromes. The article recommends individualizing each patient's treatment and discusses the use of various drugs in treating vulvodynia, including antidepressants such as tricyclic antidepressants and extended release venlafaxine; anticonvulsants such as Neurontin, Trileptal, Gabitril, and Topamax; nonsteroidal antiinflammatory drugs such as Celebrex and Vioxx; and opioids such as Oxycontin.

Periodicals and News 67

Academic Periodicals covering Neurontin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Neurontin. In addition to these sources, you can search for articles covering Neurontin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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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 Institute12: •

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/

12

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

Physician Resources 73

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 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:14 •

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

•

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

•

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

•

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

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

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). 14 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Neurontin” (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 970 2 32 2 1 1007

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “Neurontin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

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

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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 75

Coffee Break: Tutorials for Biologists20 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.21 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.22 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/.

20 Adapted 21

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. 22 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 Neurontin 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 Neurontin. 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 Neurontin. 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 “Neurontin”:

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Other Guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Epilepsy http://www.nlm.nih.gov/medlineplus/epilepsy.html Multiple Sclerosis http://www.nlm.nih.gov/medlineplus/multiplesclerosis.html Trigeminal Neuralgia http://www.nlm.nih.gov/medlineplus/trigeminalneuralgia.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Neurontin. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Trigeminal Neuralgia: An Overview for Patients and Their Families Source: Barnegat Light, NJ: Trigeminal Neuralgia Association. 1998. 4 p. Contact: Available from Trigeminal Neuralgia Association. P.O. Box 340, Barnegat Light, NJ 08006. (609) 361-6250. Fax (609) 361-0982. E-mail: [email protected]. Website: www.tna-support.org. PRICE: Single copy free. Summary: Trigeminal neuralgia (TN) is a chronic disorder that usually affects people in middle or late life and is characterized by excruciating pain around the eyes, nose, lips, jaw, forehead, or scalp. This fact sheet provides an overview of the causes, symptoms, diagnosis, medical treatments, and surgical options for trigeminal neuralgia. TN is believed to be caused when a blood vessel presses on the trigeminal nerve (vascular compression) and causes the covering (myelin sheath) to deteriorate. This deterioration causes the nerve to send abnormal signals to the brain which can cause a soft touch or simple facial movement to feel painful. TN can be easily diagnosed by a dentist or physician familiar with its pain and symptoms. There is no specific test to confirm TN. Many patients find that TN can be effectively managed with medication, usually on an ongoing basis (at least four to six weeks on medications, then a gradual tapering off if the pain stays in remission). The most commonly prescribed medications for TN are anticonvulsants, which work by suppressing the abnormal signaling activity of the trigeminal nerve. Drugs prescribed for TN include carbamazepine (Tegretol), phenytoin

Patient Resources 79

(Dilantin), gabapentin (Neurontin), and baclofen (Lioresal, a muscle relaxant). Surgical options can include radiofrequency rhizotomy (or electrocoagulation), glycerol rhizotomy, balloon compression, microvascular decompression, and stereotactic (or gamma knife or LINAC) radiosurgery. The fact sheet concludes with information about the non profit Trigeminal Neuralgia Association (TNA), a group that sponsors support groups, a national patient network, and educational outreach (www.tna-support.org). 1 figure.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “Neurontin” (or synonyms). The following was recently posted: •

Guideline for the use of Neurontin® in the management of neuropathic pain Source: Washington State Department of Labor and Industries - State/Local Government Agency [U.S.]; 2002; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3550&nbr=2776&a mp;string=Neurontin

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 Neurontin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

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

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•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Neurontin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Neurontin. 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 Neurontin. 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 “Neurontin” (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 “Neurontin”. 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 “Neurontin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

Patient Resources 81

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 “Neurontin” (or a synonym) into the search box, and click “Submit Query.”

83

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.23

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

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

84 Neurontin

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)24: •

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/

24

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

Finding Medical Libraries 85

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

86 Neurontin

•

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 87

•

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/

88 Neurontin

•

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

89

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

91

NEURONTIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Propanol: An isomer of 1-propanol. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [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] 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] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [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] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at

92 Neurontin

a targeted site. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Ankylosis: Fixation and immobility of a joint. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] 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] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and

Dictionary 93

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] 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 vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Bullous: Pertaining to or characterized by bullae. [EU] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] 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] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an

94 Neurontin

effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [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] 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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]

Chronic: A disease or condition that persists or progresses over a long period of time. [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] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] 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

Dictionary 95

thought to involve inhibition of dopamine uptake. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [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] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] 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] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cutaneous: Having to do with the skin. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression

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applied through body openings. [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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diflunisal: A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of aspirin. [NIH] Digestive system: The organs that take in food and turn it into products that the body can 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] Dilatation: The act of dilating. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [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] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [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] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Erythromelalgia: Disease marked by paroxysmal, bilateral vasodilatation, particularly of the extremities, with burning pain, and increased skin temperature and redness. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethosuximide: An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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] Extraction: The process or act of pulling or drawing out. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Gamma knife: Radiation therapy in which high-energy rays are aimed at a tumor from many angles in a single treatment session. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gastric: Having to do with the stomach. [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.

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[NIH]

Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Glossodynia: Pain in the tongue; glossalgia. [EU] 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] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [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] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] 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] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [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]

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Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [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] Inorganic: Pertaining to substances not of organic origin. [EU] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] 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]

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] Ion Exchange Resins: High molecular weight, insoluble polymers which contain functional groups that are capable of undergoing exchange reactions (ion exchange) with either cations or anions. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a

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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] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to indomethacin. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH]

Library Services: circulation. [NIH]

Services offered to the library user. They include reference and

Ligands: A RNA simulation method developed by the MIT. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH]

Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Mefenamic Acid: A non-steroidal anti-inflammatory agent with analgesic, antiinflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment.

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Melanoma usually begins in a mole. [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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monotherapy: A therapy which uses only one drug. [EU] 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] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [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] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelin Sheath: The lipid-rich sheath investing many axons in both the central and peripheral nervous systems. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (Schwann cells in the peripheral and oligodendroglia in the central nervous system). Deterioration of the sheath in demyelinating diseases is a serious clinical problem. [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

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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] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] 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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neutralization: An act or process of neutralizing. [EU] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [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

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pharmacologically as a sympathomimetic. [NIH] Nystagmus: Rhythmical oscillation of the eyeballs, either pendular or jerky. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pentosan polysulfate: A drug used to relieve pain or discomfort associated with chronic inflammation of the bladder. It is also being evaluated for its protective effects on the gastrointestinal tract in people undergoing radiation therapy. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenazopyridine: A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity.

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[NIH]

Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: 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] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a

Dictionary 105

designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] 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] 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] 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] 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] 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] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [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] 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]

106 Neurontin

Reflux: The term used when liquid backs up into the esophagus from the stomach. [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] Response rate: treatment. [NIH]

The percentage of patients whose cancer shrinks or disappears after

Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] 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] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] 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] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or

Dictionary 107

cartilage. [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] 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] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [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]

Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic

108 Neurontin

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] 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] Trigeminal Nerve: The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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]

109

INDEX 2 2-Propanol, 47, 91 A Adjuvant, 33, 34, 35, 51, 91 Adverse Effect, 61, 91, 104, 106 Afferent, 91 Agonist, 27, 91, 92 Alternative medicine, 65, 91 Amine, 48, 91 Amino acid, 46, 47, 49, 91, 92, 100, 106, 108 Amitriptyline, 60, 91 Amyotrophy, 46, 91 Analgesic, 19, 22, 91, 96, 100, 101, 102 Analog, 4, 52, 91 Anesthetics, 60, 91 Anhydrous, 47, 52, 92 Animal model, 34, 92 Ankylosis, 52, 92 Anticholinergic, 60, 91, 92 Anticonvulsant, 11, 12, 22, 27, 28, 29, 46, 47, 92, 93, 94, 97, 100, 101, 104, 106 Antiepileptic, 11, 12, 28, 29, 34, 41, 60, 61, 64, 92 Antifungal, 22, 64, 92 Anti-inflammatory, 52, 92, 96, 98, 99, 100, 102, 106 Anti-Inflammatory Agents, 52, 92, 100 Anxiolytic, 29, 92 Aqueous, 49, 50, 92 Arginine, 60, 92 Arterioles, 52, 92, 93 Articular, 52, 92 Aspartate, 27, 92 Atrophy, 52, 92 Atropine, 60, 92 B Baclofen, 79, 92 Base, 51, 92, 96, 97, 100 Benzodiazepines, 39, 92 Benzoic Acid, 60, 92 Bioavailability, 53, 54, 92 Biotechnology, 8, 59, 65, 73, 92 Bipolar Disorder, 11, 13, 35, 78, 93 Bladder, 60, 93, 95, 101, 103, 105 Blood vessel, 78, 93, 107, 108 Branch, 27, 87, 93, 103, 107 Bullous, 18, 93

C Calcium, 19, 27, 28, 30, 60, 93, 102 Calcium channel blocker, 60, 93 Calcium Channel Blockers, 60, 93 Calcium Channels, 28, 93 Capsaicin, 16, 93 Capsules, 46, 47, 53, 64, 93, 96 Carbamazepine, 11, 12, 41, 60, 61, 78, 93 Case report, 9, 19, 93, 94 Case series, 10, 14, 93, 94 Causality, 66, 93 Cell, 91, 92, 93, 94, 97, 101, 105 Cell Death, 94 Cellulose, 48, 55, 94 Central Nervous System, 66, 93, 94, 97, 98, 101, 106 Cerebral, 20, 49, 50, 53, 55, 56, 57, 58, 94, 102 Chemotherapy, 11, 14, 40, 94 Chlorine, 50, 56, 94 Cholestasis, 8, 16, 41, 94 Chondroitin sulfate, 60, 94 Chronic, 20, 52, 66, 78, 94, 99, 103 Cimetidine, 60, 94 Climacteric, 94 Clinical study, 42, 94, 95 Clinical trial, 39, 40, 43, 73, 94, 95, 96, 105 Clonazepam, 61, 94 Cocaine, 42, 94 Cognition, 11, 95 Comorbidity, 11, 95 Complementary and alternative medicine, 33, 37, 95 Complementary medicine, 33, 95 Complete remission, 95, 106 Computational Biology, 73, 95 Consumption, 9, 49, 95 Contraindications, ii, 95 Controlled clinical trial, 13, 95 Controlled study, 10, 12, 26, 95 Convulsive, 49, 95 Cranial, 50, 53, 55, 56, 57, 58, 95, 98, 102, 103, 108 Cromolyn Sodium, 60, 95 Crystallization, 49, 95 Cutaneous, 8, 16, 95 Cystitis, 60, 95

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D Decompression, 79, 95 Dementia, 96 Density, 46, 47, 96, 105 Detoxification, 39, 96 Diabetes Mellitus, 3, 96 Diagnostic procedure, 45, 65, 96 Diflunisal, 52, 96 Digestive system, 43, 96 Dilatation, 52, 96 Direct, iii, 96, 105 Dizziness, 4, 42, 96 Dorsal, 27, 96 Dosage Forms, 53, 54, 96 Dose-dependent, 54, 96 Double-blind, 10, 12, 14, 15, 16, 17, 23, 26, 96 Double-blinded, 14, 96 Drug Evaluation, 42, 96 Drug Interactions, 41, 96 Duodenum, 54, 96 Dystrophy, 28, 96 E Efficacy, 11, 26, 29, 42, 61, 97 Electrocoagulation, 79, 97 Environmental Health, 72, 74, 97 Eosinophilia, 21, 97 Erythromelalgia, 14, 97 Escalation, 22, 97 Essential Tremor, 26, 65, 97 Ethanol, 14, 47, 49, 97 Ether, 49, 97 Ethosuximide, 61, 97 Excipients, 48, 55, 97 Excitability, 97, 102 Extraction, 10, 97 F Facial, 78, 97 Family Planning, 73, 97 Fluorescence, 10, 97 G Gamma knife, 79, 97 Ganglion, 27, 97, 108 Gastric, 54, 94, 96, 97 Gene, 59, 93, 97 Generator, 98 Genitourinary, 20, 28, 98 Glossodynia, 11, 98 Glucocorticoids, 52, 98 Glutamate, 98, 106 Glycerol, 79, 98 Grade, 49, 98

Gravis, 22, 98 H Headache, 12, 15, 16, 21, 42, 98 Hemicrania, 21, 98 Hemodialysis, 17, 98 Hepatotoxicity, 21, 98 Heterodimer, 28, 98 Hormone, 35, 98 Hormone Replacement Therapy, 35, 98 Hydrocortisone, 52, 98 Hydrogen, 53, 91, 92, 98 Hydrolysis, 46, 47, 99 Hydroxyzine, 60, 99 Hyperalgesia, 16, 18, 26, 99 Hypokinesia, 49, 50, 53, 55, 99 I Id, 30, 36, 79, 86, 88, 99 Impairment, 94, 99, 101, 105 Indomethacin, 21, 99, 100 Inflammation, 27, 52, 92, 95, 98, 99, 103, 107, 108 Inorganic, 48, 50, 99 Insomnia, 42, 99 Interferon, 33, 99 Interferon-alpha, 33, 99 Interstitial, 60, 99 Intubation, 17, 99 Invasive, 60, 99 Ion Exchange, 49, 94, 99 Ion Exchange Resins, 49, 99 Ions, 50, 92, 93, 98, 99, 100 Isoelectric, 50, 100 Isoelectric Point, 50, 100 Isoleucine, 100 K Kb, 72, 100 Ketorolac, 52, 100 Ketorolac Tromethamine, 52, 100 L Leucine, 100 Library Services, 86, 100 Ligands, 28, 100 Lithium, 51, 100 Liver, 41, 92, 96, 98, 100 Liver Transplantation, 100 Localized, 52, 66, 100 Lorazepam, 39, 100 M Malignancy, 18, 100 Mania, 15, 33, 100 Mastectomy, 9, 100 Medicament, 46, 51, 100

Index 111

MEDLINE, 73, 100 Mefenamic Acid, 52, 100 Melanoma, 33, 100 Memantine, 101 Membrane, 50, 93, 97, 101, 104 Mental, v, 42, 44, 72, 74, 95, 96, 99, 100, 101, 105, 106 Mental Disorders, 44, 99, 101, 105 Metabolite, 53, 99, 101, 105 Methanol, 47, 49, 101 Methylene Blue, 60, 101 Mexiletine, 22, 101 MI, 9, 26, 46, 47, 51, 52, 89, 101 Migration, 52, 101 Molecular, 9, 22, 50, 73, 75, 93, 95, 99, 101, 108 Monotherapy, 3, 10, 17, 42, 101 Morphine, 9, 101, 102 Multiple sclerosis, 35, 101 Muscle relaxant, 60, 79, 101, 104 Myasthenia, 22, 101 Myelin, 78, 101 Myelin Sheath, 78, 101 Myoclonus, 34, 101 N Naltrexone, 102 Naproxen, 52, 102 Narcosis, 51, 56, 57, 58, 102 Narcotic, 60, 101, 102 Nausea, 11, 42, 96, 102 NCI, 1, 39, 40, 43, 71, 102 Need, 3, 51, 53, 55, 56, 57, 58, 60, 66, 80, 102 Neocortex, 19, 102 Nerve, 65, 78, 91, 97, 101, 102, 103, 104, 106, 108 Neuralgia, 10, 17, 78, 102, 104 Neuronal, 16, 19, 93, 102 Neurons, 28, 94, 101, 102 Neuropathy, 3, 40, 91, 102, 103 Neurotoxicity, 40, 102 Neutralization, 49, 102 Nifedipine, 60, 102 Norepinephrine, 28, 91, 102 Nystagmus, 19, 103 O Ocular, 103 Ophthalmoplegia, 15, 103 Outpatient, 3, 39, 41, 103 Overdose, 10, 20, 103 P Paclitaxel, 35, 103

Paradoxical, 18, 103 Paralysis, 46, 103 Paroxysmal, 35, 97, 103 Pathologic, 52, 103 Patient Education, 78, 84, 86, 89, 103 Pelvic, 103, 105 Pentosan polysulfate, 60, 103 Peripheral Nervous System, 101, 103 Peripheral Neuropathy, 3, 40, 103 Phantom, 16, 103 Pharmacokinetics, 26, 28, 103 Pharmacotherapy, 11, 12, 14, 15, 103 Phenazopyridine, 60, 103 Phenyl, 60, 104 Phenytoin, 61, 78, 93, 104 Plasma, 10, 19, 21, 34, 52, 54, 104 Plasma protein, 52, 104 Plexus, 13, 104 Polymorphic, 48, 49, 104 Postherpetic Neuralgia, 10, 22, 36, 104 Postmenopausal, 36, 104 Postoperative, 9, 100, 104 Postsynaptic, 28, 104 Potassium, 51, 104 Potentiates, 35, 104 Potentiating, 51, 56, 57, 58, 91, 104 Practice Guidelines, 74, 79, 104 Prednisolone, 52, 104 Presumptive, 20, 104 Prevalence, 104 Prodrug, 53, 105 Progressive, 46, 96, 97, 105 Prophylaxis, 15, 105 Propranolol, 26, 105 Prostate, 14, 40, 105 Protein S, 59, 93, 105 Protocol, 41, 105 Pruritus, 41, 99, 105 Psychiatry, 9, 10, 13, 15, 17, 18, 22, 26, 105 Psychosis, 18, 105 Public Policy, 73, 105 Q Quality of Life, 4, 39, 40, 105 R Randomized, 3, 9, 10, 13, 16, 26, 40, 41, 42, 97, 105 Rarefaction, 52, 105 Receptor, 27, 94, 99, 105, 106 Refer, 1, 96, 105 Reflex, 28, 35, 105 Reflux, 49, 106 Refractory, 10, 12, 20, 27, 28, 97, 106

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Regimen, 40, 53, 97, 103, 106 Remission, 78, 93, 106 Response rate, 42, 106 Restless legs, 20, 23, 106 Riluzole, 46, 106 S Salicylate, 60, 96, 106 Satellite, 59, 106 Schizophrenia, 18, 106, 108 Sclerosis, 16, 46, 78, 101, 106 Seizures, 9, 12, 15, 20, 26, 27, 28, 41, 42, 53, 93, 94, 97, 103, 104, 106, 107 Self Care, 60, 106 Sensitization, 16, 66, 106 Serine, 29, 106 Serotonin, 60, 91, 103, 106 Side effect, 41, 42, 53, 60, 91, 96, 100, 106 Skeleton, 106 Sodium, 51, 52, 53, 60, 102, 107 Solvent, 48, 49, 51, 91, 97, 98, 101, 107 Somnolence, 4, 107 Spasticity, 35, 92, 107 Specialist, 80, 107 Spectrum, 19, 107 Spinal cord, 13, 14, 16, 19, 33, 46, 92, 94, 97, 102, 103, 105, 107 Statistically significant, 4, 107 Status Epilepticus, 17, 107 Stereotactic, 79, 107 Steroids, 60, 107 Stress, 12, 102, 107

Stroke, 9, 34, 44, 72, 107 Support group, 79, 107 Synovial, 52, 107 Systemic, 52, 104, 107 Systemic disease, 52, 107 T Thermal, 26, 107 Threshold, 27, 97, 107 Tissue, 52, 92, 93, 98, 99, 100, 101, 102, 103, 106, 107, 108 Toxicity, 17, 51, 96, 103, 107 Toxicology, 10, 17, 74, 108 Trauma, 49, 98, 108 Tremor, 15, 108 Tricyclic, 66, 91, 108 Trigeminal, 78, 108 Trigeminal Nerve, 78, 108 U Urinary, 60, 95, 98, 103, 108 V Valine, 108 Vascular, 78, 93, 108 Vasculitis, 8, 108 Vasomotor, 36, 108 VE, 108 Venlafaxine, 66, 108 Venules, 52, 93, 108 Veterinary Medicine, 73, 108 W Withdrawal, 9, 14, 17, 18, 22, 39, 108

Index 113

114 Neurontin