DONEPEZIL A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Donepezil: 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: 0-597-84578-6 1. Donepezil-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on donepezil. 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 DONEPEZIL ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Donepezil .................................................................................... 10 E-Journals: PubMed Central ....................................................................................................... 21 The National Library of Medicine: PubMed ................................................................................ 21 CHAPTER 2. NUTRITION AND DONEPEZIL...................................................................................... 63 Overview...................................................................................................................................... 63 Finding Nutrition Studies on Donepezil ..................................................................................... 63 Federal Resources on Nutrition ................................................................................................... 65 Additional Web Resources ........................................................................................................... 65 CHAPTER 3. ALTERNATIVE MEDICINE AND DONEPEZIL ............................................................... 67 Overview...................................................................................................................................... 67 National Center for Complementary and Alternative Medicine.................................................. 67 Additional Web Resources ........................................................................................................... 71 General References ....................................................................................................................... 72 CHAPTER 4. PATENTS ON DONEPEZIL ............................................................................................ 73 Overview...................................................................................................................................... 73 Patents on Donepezil ................................................................................................................... 73 Patent Applications on Donepezil................................................................................................ 77 Keeping Current .......................................................................................................................... 82 CHAPTER 5. BOOKS ON DONEPEZIL ................................................................................................ 83 Overview...................................................................................................................................... 83 Book Summaries: Federal Agencies.............................................................................................. 83 Chapters on Donepezil ................................................................................................................. 84 CHAPTER 6. PERIODICALS AND NEWS ON DONEPEZIL .................................................................. 85 Overview...................................................................................................................................... 85 News Services and Press Releases................................................................................................ 85 Academic Periodicals covering Donepezil.................................................................................... 88 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 89 Overview...................................................................................................................................... 89 U.S. Pharmacopeia....................................................................................................................... 89 Commercial Databases ................................................................................................................. 90 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 93 Overview...................................................................................................................................... 93 NIH Guidelines............................................................................................................................ 93 NIH Databases............................................................................................................................. 95 Other Commercial Databases....................................................................................................... 97 APPENDIX B. PATIENT RESOURCES ................................................................................................. 99 Overview...................................................................................................................................... 99 Patient Guideline Sources............................................................................................................ 99 Finding Associations.................................................................................................................. 101 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 103 Overview.................................................................................................................................... 103 Preparation................................................................................................................................. 103 Finding a Local Medical Library................................................................................................ 103 Medical Libraries in the U.S. and Canada ................................................................................. 103 ONLINE GLOSSARIES................................................................................................................ 109 Online Dictionary Directories ................................................................................................... 109
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DONEPEZIL DICTIONARY........................................................................................................ 111 INDEX .............................................................................................................................................. 151
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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 donepezil 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 donepezil, 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 donepezil, 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 donepezil. 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 donepezil, 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 donepezil. 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 DONEPEZIL Overview In this chapter, we will show you how to locate peer-reviewed references and studies on donepezil.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and donepezil, 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 “donepezil” (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: •
Is the Placebo Control Obsolete in a World After Donepezil and Vitamin E? Source: Archives of Neurology. 55(11): 1420-1424. November 1998. Summary: This article addresses how known effective therapies for Alzheimer's disease (AD) should guide the choice of proper control processes in future AD clinical trials, particularly in light of the effective therapeutic drugs for AD produced from research on donepezil and vitamin E. It explains how the ethics of research involving the cognitively impaired sets standards for appropriate research risks and benefits that may outweigh the reasons for placebo control. It discusses choosing the best research design between placebo or active control to help assure the research community that a trial will change clinical practice and is potentially beneficial to subjects. The issue of informed consent, and proxy consent, when a cognitively impaired subject would be participating in an AD research trial also is addressed. The authors reveal that state legislation forbids AD
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research involving proxy consent 1) if the research risk is judged to be too high or 2) the possibility of direct benefit to the patient is too low or nonexistent. They then presents a way that risk and benefit assessment can settle clinical uncertainties: the condition of equipoise, where caregivers, patients or patient advocates, and the medical community negotiate clinical trial design. 35 references. •
Aricept: A Well-Tolerated and Clinically Effective Treatment for the Symptoms of AD-Results From World-Wide Clinical Trials Source: Alzheimer's Reports. 1(Supplement 1): S13-S14. November 1998. Summary: This article discusses donepezil hydrochloride (trade name: Aricept or E2020), the first selective cholinesterase inhibitor (ChEI) marketed for treating Alzheimer's disease (AD). The decline of cognitive function in AD is associated with deterioration in the cholinergic system in the cerebral cortex and other regions of the brain. The most successful therapeutic strategy to date delays the breakdown of acetylcholine (ACh) by inhibiting the enzyme acetylcholinesterase (AChE). The authors discuss the preclinical and clinical studies carried out and conclude that donepezil hydrochloride improves cognition and global function in patients with mild to moderately severe AD. 4 references.
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Effect of Donepezil Therapy on Health Costs in a Medicare Managed Care Plan Source: Managed Care Interface. 15(3): 63-70. March 2002. Summary: This article estimates the effect of donepezil therapy on health care costs in a large Medicare managed care plan. Patients with a diagnosis of Alzheimer's disease (AD) or related dementia were identified from the claims-and-encounters records of the plan. Costs for 204 patients with AD who were receiving donepezil were compared with a matched group of 204 AD patients who were not receiving donepezil. After controlling for age, gender, pharmacy benefits, comorbid conditions, and complications of dementia, annual costs for medical services and prescription drugs were found to be $3,891 lower for the donepezil group ($8,056 versus $11,947). Patients receiving longerterm therapy (270 days or longer) had greater savings ($4,192) than those receiving shorter-term therapy ($3,579). The results suggest that donepezil may be a cost-saving therapy for AD patients in Medicare managed care. 2 figures, 5 tables, 29 references.
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Impact of Donepezil on Caregiving Burden for Patients With Alzheimer's Disease Source: International Psychogeriatrics. 12(3): 389-401. September 2000. Summary: This article examines the effect of donepezil on caregiving burden reported by people caring for patients with Alzheimer's disease (AD) in the community. A selfadministered, nationwide survey of AD caregivers was used to match caregivers of patients treated with donepezil (n=274) to caregivers of patients not treated with donepezil (n=274). Matches were based on the age and physical health status of the caregiver. The Caregiver Burden Scale was used to measure time demands and distress associated with commonly performed caregiving tasks. Both groups of participants were an average of 60 years old, mostly female (77 percent), and mostly white (86 percent). There were more spouses in the donepezil group (52.6 percent) than in the non- donepezil group (40 percent). The donepezil caregivers reported significantly less difficulty for 10 of 15 caregiving tasks compared with non-donepezil caregivers, but the two groups did not differ with respect to reported demands on time. The authors conclude that better management of AD symptoms with donepezil treatment may reduce some of the burden of caregiving. 4 tables, 39 references.
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Donepezil for Mild and Moderate Alzheimer's Disease (Cockrane Review) Source: Cochrane Database of Systematic Reviews. 1: CD001190. 2001. Summary: This article presents a systematic review of clinical trials using donepezil as a treatment for mild and moderate Alzheimer's disease (AD). The Cochrane Dementia and Cognitive Improvement Group's specialized register was searched to identify all unconfounded, double blind, randomized controlled trials in which donepezil was compared with placebo for AD patients. Eight trials involving a total of 2,664 patients were included. The trials were of 12, 24, or 52 weeks duration in selected patients. Outcome data were available for cognitive function and global clinical state but not for several other important dimensions of outcome. Compared with placebo, both 5 and 10 mg/d of donepezil resulted in a significant improvement in cognition at 24 weeks, as did 10 mg/d of donepezil at 52 weeks. Results of three studies showed some improvement in global cognitive state in patients treated with 5 and 10 mg/d of donepezil compared with placebo at 12 and 24 weeks. However, patients' own ratings of quality of life showed no benefit of donepezil over placebo. More incidents of nausea, vomiting, diarrhea, and anorexia were reported in the 10 mg/d group compared with the 5 mg/d and placebo groups, but few patients left a trial as a direct result of the intervention. 6 tables, 41 references.
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Improving Visual Memory With Aricept (Donepezil Hydrochloride, E2020) in Mildto-Moderate Alzheimer's Disease Source: Clinical Gerontologist. 24(1-2): 55-73. 2001. Summary: This article reports an improvement of visual memory with donepezil (Aricept) treatment in patients with mild to moderate Alzheimer's disease (AD). Sixteen patients completed tests of cognitive and neuropsychological function at baseline and about 16 weeks later, after treatment with donepezil. The initial dose was 5 mg (mean of 84.9 days at 5 mg), followed by 10 mg when tolerated (mean of 24.9 days). All patients significantly improved their scores on tests measuring visual memory, visuospatial skills, and auditory verbal memory after treatment with donepezil. There were no significant changes on measures of depression and anxiety, suggesting that the enhanced memory functioning could not be attributed to a general improvement in mood. The findings are consistent with those of previous studies that found an overall increase in cognitive functioning with donepezil. However, they are unique in showing specific improvement in visual memory and visuospatial skills and auditory verbal memory. 3 figures, 7 tables, 53 references.
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Effects of Donepezil on Emotional/Behavioral Symptoms in Alzheimer's Disease Patients Source: Journal of Clinical Psychiatry. 61(7): 487-492. July 2000. Summary: This article reports the effects of the reversible cholinesterase inhibitor donepezil on emotional and behavioral symptoms in patients with Alzheimer's disease (AD). Twenty-five patients with a diagnosis of AD were treated with donepezil for 1 year. For most patients, dosage was increased at 4 months from 5 to 10 mg q.h.s. The Mini- Mental State Examination (MMSE) and the CERAD Behavior Rating Scale for Dementia (CBRSD) were administered at baseline and at 1, 3, 4, and 12 months. Outcomes were compared with those for a reference group (n= 153) that received no donepezil or other anticholinesterase. Donepezil treatment was associated with improvement in MMSE and CBRSD total scores at 3 months. CBRSD depression and behavioral dysregulation scores improved transiently at 4 months. MMSE and CBRSD
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total, depression, and behavioral dysregulation scores returned to baseline levels at 12 months. In the untreated reference group, MMSE and CBRSD total scores deteriorated minimally over the 12 months. The results suggest that donepezil has a mildly positive effect on emotional and behavioral symptoms in AD in addition to its effect on cognitive function. 2 figures, 3 tables, 30 references. •
24-Week, Double-Blind, Placebo-Controlled Trial of Donepezil in Patients With Alzheimer's Disease Source: Neurology. 50: 136-145. January 1998. Summary: This journal article describes a multicenter study of the efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD). A total of 473 patients with AD, aged 50 years or older, were randomly assigned to 3 treatment groups: donepezil 5 mg/d (n=154), donepezil 10 mg/d (n=157), and placebo (n=162). The patients were assessed at baseline and every 6 weeks thereafter with the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-COG), the Clinician's Interview Based Assessment of Change-Plus (CIBIC Plus), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and a patient-rated quality of life scale (QOL). Both the 5 mg/d and 10 mg/d donepezil groups showed significant improvement on the ADAS-COG, CIBIC Plus, MMSE, and CDR-SB compared with the placebo group; there was no consistent effect on the QOL measure. Cholinergic side effects occurred more often in the 10 mg/d donepezil group than in either the 5 mg/d or placebo group, but they were transient and generally mild in severity. The authors conclude that donepezil may improve cognitive and global function in patients with mild to moderate AD. 7 figures, 4 tables, 33 references.
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Purpuric Rash With Donepezil Treatment Source: BMJ. 317: 787. September 19, 1998. Summary: This journal article describes a reaction to the drug donepezil in an 82 year old woman with Alzheimer's disease. While previously reported side effects to donepezil have been gastrointestinal, this is the first report of a purpuric rash associated with the drug. Donepezil was thought to be the cause of the skin rash because it occurred with initial treatment, cleared when the drug was stopped, and reoccured when donepezil was started again. 2 references, 1 figure.
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Addition of Vitamin E to Donepezil as a Treatment for Alzheimer's Disease Source: Alzheimer's Reports. 2(3): 143-146. 1999. Summary: This journal article describes a study comparing donepezil alone and donepezil with vitamin E in the treatment of mild to moderate Alzheimer's disease (AD). Nineteen patients with probable AD, mean age 73.63 years, were randomly assigned to receive either 5 mg of donepezil alone or 5 mg of donepezil plus 1,200 mg of vitamin E daily for 12 weeks. All participants were assessed at 6 and 12 weeks with the Mini-Mental State Examination, Clinical Global Improvement scale, Empirical Behavioral Pathology in Alzheimer's disease scale, and a measure of extrapyramidal symptoms. No significant differences in efficacy or safety were found between the two treatment regimens. Patients with behavioral symptoms were more likely to improve on the combined regimen, but the difference was not significant and was lost after week 12. The authors conclude that the combined therapy should be studied for a longer period of time. 2 tables, 12 references
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Donepezil Improves Symptoms of Delirium in Dementia: Implications for Future Research Source: Journal of Geriatric Psychiatry and Neurology. 11: 159-161. Fall 1998. Summary: This journal article discusses a case study of delirium, complicated by preexisting dementia, that was resolved rapidly following initiation of the cholinesterase inhibitor donepezil. The authors suggest that cholinergic dysfunction may have played a role in the etiology of the patient's delirium. Delirium is a common complication of dementia that may produce agitation, which may be refractory to conventional medications such as antipsychotics and benzodiazepines. Delirium may also produce considerable morbidity. Delirium is not always reversible and there is no specific treatment for persistent delirium; the main treatment approach is to treat the underlying medical problem. The authors state that future research needs to be directed at the issue of cholinergic activity in delirium through monitoring serum anticholinergic activity and its response to procholinergic therapy. 17 references. (AA-M).
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Donepezil for Treatment of Dementia With Lewy Bodies: A Case Series of Nine Patients Source: International Psychogeriatrics. 10(3): 229-238. September 1998. Summary: This journal article discusses a study of nine Canadian patients (seven males, two females; 67-84 years) with dementia with Lewy bodies (DLB) who had been treated previously with donepezil (2.5-5.0 mg/day in 4 patients, and 10 mg/day in 5 patients). The symptoms evaluated included hallucinations, parkinsonism, and decreased cognitive and functional abilities. Cognition improved in seven of the nine patients, remained the same in one, and fluctuated in one according to cognitive testing and family reports. Six of the nine patients demonstrated an improved or stable level of functioning. This fluctuated in the other two patients. Hallucinations decreased in frequency and duration in eight of the nine patients; one patient reported worse hallucinations initially and then fluctuation in hallucinations. Treatment with donezepil was associated with worsening parkinsonism in three of the patients, but they responded to treatment with levodopa/carbidopa. The authors concluded that treatment of DLB patients with donezepil for 12 weeks often improved hallucinations and sometimes improved cognition and overall function. 2 tables, 23 references (AA-M).
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Relationship Between Donepezil and Behavioral Disturbances in Patients With Alzheimer's Disease Source: American Journal of Geriatric Psychiatry. 8(2): 134-140. Spring 2000. Summary: This journal article examined the relationship between donepezil use and behavioral disturbances in patients with Alzheimer's disease (AD). Caregivers of AD patients completed a survey twice at a six month interval. Patients taking donepezil had significantly lower levels of behavioral disturbances than those not taking the medication. Donepezil users were described as less likely to be threatening, destructive, or disruptive. Caregivers of donepezil users also reported being less upset by the patient's behaviors, but the difference between groups was not significant. Significantly fewer donepezil users than non-users were treated with sedatives. These findings add to the evidence that cholinesterase inhibitors may reduce behavioral disturbances in patients with AD. 2 figures, 4 tables, 30 references.
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Sustained Cognitive Improvement Following Treatment of Alzheimer's Disease With Donepezil Source: International Journal of Geriatric Psychiatry. 15: 50-53. 2000. Summary: This journal article examines responses to the anticholinesterase inhibitor donepezil (Aricept) in people referred to a specialist memory clinic. Participants were 282 individuals referred to a British clinic with the diagnosis of probable mild to moderate Alzheimer's disease (AD). Results indicated that over 65 percent of participants had improved cognitive functioning at 3 months. There was significantly more improvement in people under age 64 years. Caregiver and professional reports of behavioral improvement did not always relate to cognitive improvement. There was a trend toward increased improvement in people on concomitant antidepressant drug therapy. The researchers conclude that younger people should be targeted for early assessment and treatment. 1 table, 12 references.
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Defining Meaningful Change in Alzheimer's Disease Trials: The Donepezil Experience Source: Journal of Geriatric Psychiatry and Neurology. 12: 39-48. Spring 1999. Summary: This journal article looks at recent clinical trials of donepezil to illustrate how the efficacy of a new therapy for Alzheimer's disease (AD) is evaluated. Regulatory guidelines in the United States and Europe generally require that a drug specifically indicated for treating AD must demonstrate an effect on the core manifestations of dementia. Progressive declines in cognition and function are the defining features of AD. In the United States, current guidelines require that new AD treatments show effectiveness on performance-based measures of cognition and on clinician rated global assessments. European guidelines also emphasize improvement in function. The primary instruments that have been used to evaluate changes in cognition and global function in most recent AD trials are the cognitive subscale of the Alzheimer's Disease Assessment Scale and a version of the Clinician's Interview Based Impression of Change, respectively. This article uses key results from recent trials of donepezil to illustrate how these tools are used to establish the efficacy of a new treatment for AD. 7 figures, 1 table, 46 references.
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Cost-Effectiveness of Donepezil in the Treatment of Mild or Moderate Alzheimer's Disease Source: Neurology. 52: 1138-1145. April 1999. Summary: This journal article presents a cost-effectiveness analysis of donepezil in treating patients with mild or moderate Alzheimer's disease (AD). The authors developed a model to estimate the incremental cost-effectiveness of donepezil compared with no treatment. They determined costs per quality-adjusted life-years gained, and projected the progression of AD patients into more severe disease stages and nursing home admission. Data from a randomized clinical trial of donepezil were used to assess the drug's effects on the 6-week probability of progression. Data on costs and health-related quality of life (HRQL) associated with different disease stages and settings were taken from published estimates and a companion cross-sectional study, respectively. The results suggest that the cost of donepezil is partially offset by a reduction in the costs of care due to enhancement of cognitive functioning and delay in progression to more costly disease stages and settings. The magnitude of the cost offset and effect on HRQL depend on assumptions about the duration of the drug's effect, for which controlled data are lacking. If the drug effect exceeds 2 years, the model predicts
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that for mild AD the drug would pay for itself in costs offset. 2 figures, 5 tables, 32 references. (AA-M). •
Donepezil Therapy in Clinical Practice: A Randomized Crossover Study Source: Archives of Neurology. 57: 94-99. January 2000. Summary: This journal article reports the efficacy of donepezil hydrochloride for the treatment of Alzheimer's disease (AD) in clinical practice. Sixty patients from the memory disorders units of two hospitals in Boston, Massachusetts, were enrolled in a randomized, placebo-controlled, double-blind crossover study. All patients completed a 6-week placebo wash-in period, followed by random assignment to one of two treatment sequences: 6 weeks each of placebo treatment, donepezil therapy, and placebo washout; or 6 weeks each of donepezil therapy, placebo washout, and placebo treatment. The main outcome measure was change in scores on the Alzheimer's Disease Assessment Scale cognitive subscale. Among the 48 patients who completed treatment and testing for both periods, subscale scores improved 2.17 points during donepezil therapy compared with placebo therapy. Scores returned to baseline within 3 weeks of drug washout. Contrary to studies with tacrine (Cognex), the presence of the apolipoprotein E4 allele did not predict treatment failures. Most of the adverse events related to donepezil therapy were not severe. The authors conclude that donepezil therapy modestly improves cognition in patients with AD drawn from clinical practice. 2 figures, 4 tables, 24 references.
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Donepezil Source: Drugs and Aging. 10(3): 234-241. March 1997. Summary: This journal article reviews the actions, efficacy, and safety of donepezil in the treatment of patients with Alzheimer's disease (AD). It describes the inhibitory effects of donepezil on cholinesterase activity in tissues and animal studies, and the pharmacokinetics of donepezil in patients with AD and healthy volunteers. Findings from clinical trials in patients with mild to moderate AD revealed that doses of donepezil of 5 or 10 mg/day were associated with significant improvements on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) after 14 and 30 weeks, and on a measure of global function after 30 weeks. After 2 years of treatment, the ADAS-cog score of treated patients with AD was about 4 points better than would be expected in untreated patients. The most commonly reported adverse effects were gastrointestinal problems and dizziness; no toxic effects on liver function were reported after 12 weeks of treatment. Two guest commentaries follow the article. In the first comment, Richard C. Mohs notes that donepezil appears to have all the beneficial effects of tacrine but has less adverse effects and is easier to administer. More studies are needed to document effects of using it for long-term treatment. In the second comment, Peter J. Whitehouse observes that donepezil has theoretical advantages over tacrine and its practical advantages will allow it to be used successfully by more patients. However, no evidence exists that shows donepezil slows the progression of AD by affecting neuronal viability. 4 figures, 1 table, 26 references.
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Donepezil: Pharmacoeconomic Implications of Therapy Source: Pharacoeconomics. 16(1): 99-114. July 1999. Summary: This journal article reviews the literature on the pharmacoeconomics of donepezil. Donepezil is a specific acetylcholinesterase inhibitor that can improve the symptoms of mild to moderate Alzheimer's disease (AD). In these patients, cognitive
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function may be maintained above baseline levels for up to 1 year, and normal decline of cognitive function is slowed. Neuropsychiatric symptoms and the ability to perform daily activities also may be improved by donepezil, but data are limited. Donepezil is not expected to alter the underlying neurodegenerative process, and response to the drug varies between individuals. In the absence of validated instruments to measure quality of life, it is not clear how donepezil affects this parameter. In a United States (US) survey of AD patients being cared for at home, treatment with donepezil over a 6month period did not increase overall direct medical costs. The authors conclude that the cost effectiveness of donepezil may depend largely on the ability of the drug to improve the patient's daily functioning and behavior (thereby reducing caregiver burden) and to delay institutionalization. 4 figures, 2 tables, and 65 references. •
Donepezil for Dementia With Lewy Bodies: A Case Study Source: International Journal of Geriatric Psychiatry. 14: 69-74. 1999. Summary: This letter to the editor reports on a patient with dementia with Lewy bodies (DLB) who had prominent visual hallucinations and who showed a marked response to treatment with donepezil. The authors describe the patient's presenting history, clinical evaluation, and treatment program. After treatment with donepezil, the patient had less visual hallucinations and showed improvement in cognition and performing activities of daily living. The authors believe that treatment with donepezil was the main reason for the improvement; they state that this is the first report of a patient with DLB who showed an early, marked, and enduring response after treatment with a cholinesterase inhibitor. Future clinical studies of cholinesterase inhibitors should explore safety and efficacy in patients with DLB. (1 figure, 1 table, 11 references)
Federally Funded Research on Donepezil The U.S. Government supports a variety of research studies relating to donepezil. 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 donepezil. 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 donepezil. The following is typical of the type of information found when searching the CRISP database for donepezil: •
Project Title: A CLINICAL TRIAL OF DONEPEZIL FOR DOWN SYNDROME Principal Investigator & Institution: Kishnani, Priya S.; Assistant Professor; Pediatrics; Duke University Durham, Nc 27706
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract): The primary hypotheses of the proposed project is that administration of Donepezil to young adults with Down syndrome (DS) will improve adaptive functioning and expressive language as measured by a change from baseline to endpoint at 24 weeks of therapy. DS is the most common genetic cause of mental retardation worldwide. Cognitive and functional deficits, of variable degree, are seen in all subjects with DS and currently there is no approved treatment for these domains. An impaired cholinergic system, which persists throughout the lifespan, has been detected early in life in individuals with DS. This cholinergic deficit is believed to underlie many of the cognitive and functional impairments in DS. A therapy that increases the bioavailability of acetylcholine could produce improvements in cognition and consequently, adaptation in DS. Alzheimer's disease (AD) is a model for this effect. Donepezil Hydrochloride, an FDA-approved second generation cholinesterase inhibitor, is currently the most widely-used medication for the pharmacotherapy of cognitive and functional deficits in AD. A previous open label study of DS adults found Donepezil to be well tolerated with improvement in expressive language and adaptive domains. Rationale for its use in young DS individuals is to enhance availability of acetylcholine because of its key role in learning and not to treat symptoms of AD in DS. The proposed study is a single Center, randomized 24-week double-blind, placebo-controlled study with a subsequent 24-week open treatment and six-week washout phases. Sixty individuals with DS will participate, and half will receive drug during the first 24 weeks. The primary endpoints are the adaptive behavior composite score of the Vineland Adaptive Behavior Scales (VABS) and expressive language subtests of the Clinical Evaluation of Language Fundamentals (CELF-3) comparing the treated group to the control group after the 24 weeks of blinded treatment. A number of secondary aims will investigate effects of treatment of specific components of cognition, i.e., memory and mood. Safety and tolerability will also be evaluated. As DS individuals are now living longer, improving their quality of life and maximizing their developmental potential are of paramount importance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITIVE ENHANCERS EXPLORED WITH PET IMAGING Principal Investigator & Institution: Schultz, Susan K.; Associate Professor; Psychiatry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 30-JUN-2004 Summary: (provided by applicant) This application responds to PA-99- 134, using the Exploratory/Development Grant for Intervention Pilot Research (R2 1) mechanism. The overarching goal of this proposal is to investigate how cognitive enhancing agents affect functional brain activity in elderly subjects early in the course of cognitive decline. This study will also determine whether a novel combination of agents may have enhanced or distinct effects on brain activity and cognition. Specifically, we propose a placebocontrolled trial of the cholinesterase inhibitor donepezil in the treatment of elderly subjects with mild cognitive impairment. We will also test whether augmentation with another agent, ginkgo biloba extract (GBE), may increase the therapeutic benefit. Outcome measures will include cognitive testing as well as an assessment of functional brain activity during a verbal recall activation task using H20 positron emission tomography (PET). Treatment effects on cognition, cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in elderly adults (over 65 years) will be examined. The treatment trial will be encompass a one year period, with initially a six
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month placebo-controlled donepezil trial followed by randomization to donepezil with and without GBE augmentation for a subsequent six month treatment period. PET imaging will be performed at intake, six months and one year to isolate the effects of each treatment condition. The PET imaging will assess brain activity during a specific memory activation task, and also during an acetazolamide challenge to measure total vasodilatory capacity. This will allow the investigators to determine whether treatment is associated with increased CBF during the cognitve task and/or associated with changes in cerebrovascular reserve (CVR). At the present time, there are no defmitive treatments for cognitive deterioration. The poor prognosis of dementia necessitates that every therapeutic option be investigated with rigorous scientific methods. The therapeutic effects of cholinesterase inhibitors have not yet been definitively mapped to regional changes in cerebral activity, nor have they been mapped to specific cognitive tasks. Similarly, GBE is currently being used widely, both in the context of dementia in the healthy adult population, yet the effects of this agent on cerebral blood flow and its relationship to cognition have not been quantified. The possible therapeutic effects of GBE should be tested through placebo-controlled, double-blinded research designed to objectively measure relevant disease parameters. This study will add to a foundation for future research on the use of cholinesterase inhibitors and/or GBE in specific neurodegenerative states (e.g., vascular dementia) by establishing their effects on CNS hemodynamics and cognitive function in the elderly adult. This study will specifically examine subjects with early cognitive impairment with the idea that clinical benefits may be detectable over long-term treatment due to both neuroprotective and direct flow effects, and that this particular population may benefit to the greatest extent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTICOLIMBIC DEGENERATION AND TREATMENT OF DEMENTIA Principal Investigator & Institution: Csernansky, John G.; Gregory B. Couch Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 06-DEC-2000; Project End 30-NOV-2004 Summary: (Adapted from applicant's abstract) Neuronal loss occurs in the hippocampus and other related brain areas during the development of Alzheimer's disease. Since the anatomic integrity of the hippocampus has been shown in both animals and humans to be a critical for memory, neurodegeneration of this brain structure may form the basis for memory losses in patients with dementia of the Alzheimer type (DAT). While cholinesterase inhibitors have been shown to ameliorate memory losses in patients with DAT, not all patients improve with treatment. Unfortunately, because we cannot predict how patients will respond, many patients with DAT are needlessly exposed to the substantial costs and side effects of ineffective therapy. Hippocampal neurons receive cholinergic afferents from the nucleus basalis of Meynert. In this project, we propose to test the hypothesis that the integrity of such neurons determines the outcome of cholinesterase inhibitor therapy, using two experimental approaches: 1) predicting the outcome of donepezil treatment in DAT subjects using in vivo neuromorphometry of the hippocampus and related brain structures, and 2) examining the effects of cholinomimetics on memory-related tasks in animals subjected to pharmacologic, excitotoxic and metabolic lesions of the hippocampus. While the first experiment has direct clinical application, the animal model experiments are critical for determining the neurobiological basis of any relationship between hippocampal neurodegeneration and treatment responsiveness in patients with DAT. Specific Aim 1: Fifty subjects with very mild-to mild DAT will be recruited from the Memory Diagnostic Center at Washington
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University to receive a high resolution MR scan and open label treatment with donepezil for two years. Clinical assessments will occur every three months. High resolution MR scans will be analyzed with high dimensional brain mapping tools to assess the volume and shape characteristics of the hippocampus and related brain structures. Specific Aim 2: The efficacy of cholinomimetic drugs will be studied in three animal models of hippocampal neurodegeneration: 1) pharmacological blockade of NMDA receptors using MK-801; 2) excitotoxic lesions of the hippocampus: and 3) transgenic mice expressing mutant forms of human genes encoding amyloid precursor protein and presenilin 1. In each of these animal models, memory-related deficits occur that are similar to memory deficits in DAT patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DONEPEZIL HCL: TREATING COGNITIVE DEFICIT IN AUTISM Principal Investigator & Institution: Handen, Benjamin L.; Associate Professor and Program Director; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Children with autism spectrum disorders (ASD) are characterized by deficits in social interaction, impaired communication, and repetitive and stereotyped patterns of behavior, interests, and activities (APA, 1994). Interest in the amelioration of some of the core and secondary features of ASD has led the use of a wide range of pharmacological interventions, with inattention and overactivity, ritualistic behavior, self-injury and agitation/aggression among the most frequently targeted symptoms. Recent survey data indicates that up to 34 percent of individuals with ASD are prescribed medication and/or vitamins for control of a wide range of behaviors (Aman et al., 1995). While most pharmacological research to date has attempted to treat many of the behavioral deficits commonly associated with ASD, few pharmacological studies have attempted to ameliorate the core features of this disorder (an area of particular interest for this RFA). Donepezil HC1, a cholinesterase inhibitor which increases brain levels of acetylcholine, is purported to enhance cognitive functioning in a range of disorders, including multiple sclerosis, Alzheimer's disorder, and ADHD. A recent open-label study of the safety and efficacy of donepezil HC1 in 25boys with ASD found significantly increased speech production and a statistical trend toward improvement in core symptoms of ASD (Chez et al., 2000). The present application will provide an opportunity to conduct further pilot testing of the tolerability, safety and effect of donepezil HCl on the cognitive deficits presumed to underlie the core features of ASD. Forty children and adolescents with ASD will be recruited to participate in a 10-week, double blind, placebo-controlled parallel groups study of donepezil HC1. This feasibility study is designed to provide documentation of medication-enhanced cognitive functioning in ASD using a 5mg and 10 mg/day donepezil HC1 dose. This study will also examine the side effects profile of donepezil HC1 in children with ASD, explore possible correlates of treatment response, and provide an opportunity to obtain initial pilot data to determine the sample size needed to conduct a full-scale intervention trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DONEPEZIL HYDROCHLORIDE (ARICEPT) PHARMACOKINETICS Principal Investigator & Institution: Bolton, W. Kline.; Professor and Chief; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904
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Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN MODULATION OF BRAIN ABETA METABOLISM IN VIVO Principal Investigator & Institution: Gandy, Samuel E.; Director; Psychiatry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 15-DEC-2000; Project End 30-JUN-2002 Summary: Description (From the Applicant's abstract): Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation in the brain o aggregated forms of the 40- and 42-amino acid amyloid about peptide (AB340, AB42). Epidemiological studie indicate that estrogen replacement therapy (ERT) in postmenopausal women appears to decrease the risk of AD or to delay its onset, but the mechanism by which estrogen exerts this neuroprotective role remains elusive Evidence suggests that physiological concentrations of 176-estradiol reduce the release of AB40 and AB42 peptides by primary neuronal cultures from rat, mouse or human embryonic cerebral cortex, providing a possible mechanism by which ERT may act. In order to test whether estrogen modulates the metabolism of AB peptides in vivo, we propose in Aim 1 of this application to investigate the effects of ovariectomy (ovx) and estrogen replacement on brain AB40 and At342 levels in guinea pigs. We also propose to determine whether estrogen action on brain is likely to involve conventional estrogen receptors by treating ovx animals with estrogen during the concomitant administration of the estrogen receptor antagonist tamoxifen or its active metabolite, 4 hydroxytamoxifen. We will also assess the potential "agonist" or "antagonist" activity of the enantiomer, 17 alpha-estradiol, which is inactive at the best studied conventional estrogen receptor, estrogen receptor alpha. Finally, since hormonal treatment of cultured cells has been demonstrated to potentiate the nonamyloidogenic processing of the the Alzbeimer amyloid precursor when cholinergic stimuli are applied, we will also test whether brain AB340 and AB42 levels are (as predicted by the cell culture model) sharply diminished when 17B-estradiol and the clinically relevant cholinesterase inhibitor donepezil are administered simultaneously. Since one molecular explanation for estrogen action on brain AB could involve the inhibition of B-secretase activity, we will measure soluble APP-D and BACE mRNA levels in the brains of control, ovx and pharmacologically treated guinea pigs. In Aim 2, we propose to generate transgenic mice utilizing genetically engineered chimeri molecules from which AD is generated only in restricted subcellular compartments. These mice will be subjected to ovariectomy or sham surgery, and their brain AB40 and AB42 ievels will be determined. This study will implicate the subcellular compartment(s) which contain hormonesensitive AB-generating machinery. Taken together, these data will test whether the currently available neuronal cell culture data on hormonal regulation of AB metabolism are relevant in the brain of living experimental animals. In addition, novel insights will be gained into the roles of certain subcellular compartments as sites of estrogensensitive AB metabolism and into the roles (if any) in estrogen-sensitive AB metabolism which are played by the conventional estrogen receptor (estrogen receptor alpha) and/or the expression or activity of B-secretase (the rate-limiting enzyme for AD generation). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MAINTENANCE THERAPIES IN LATE-LIFE DEPRESSION-III Principal Investigator & Institution: Reynolds, Charles F.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-MAR-1989; Project End 28-FEB-2009 Summary: (provided by applicant): In this second competing continuation of R37 MH43832-16 ("Maintenance Therapies in Late Life Depression": MTLD-III), we aim to investigate pharmacologic strategies for improving and stabilizing cognitive functioning in late-life depression and minimizing progression of cognitive and associated functional impairment. Cognitive impairment in late-life depression has not been adequately addressed in previous intervention research, is a core feature of the illness, contributes markedly to disability and impaired quality of life, and is an overlooked but potentially critical target of intervention. Data from the current MTLD-II study suggest that Mild Cognitive Impairment is highly prevalent in late-life depression; and that treating depression does not normalize cognitive functions and does not prevent their progression, e.g., patients continue to demonstrate loss of memory and of executive functions despite continued recovery from depression on SSRI pharmacotherapy with paroxetine. Therefore, in MTLD-III, we will test a pharmacologic strategy involving the cholinesterase inhibitor (ChEI) donepezil, in combination with maintenance citalopram therapy (CIT + DON), to improve and to maintain cognitive functioning and functional competence in elderly patients with major depression. This work will be pursued collaboratively with our Alzheimer Disease Research Center. We hypothesize that citalopram (CIT) combined with donepezil (DON) will be superior to CIT combined with placebo/clinical management in: (1) improving cognitive performance; and (2) slowing progression of cognitive impairment and decline in functional competence. Two hundred patients aged 70 and above in current episodes of major depression will be recruited. Those who respond to antidepressant pharmacotherapy with citalopram (or to venlafaxine, in the case of citalopram non-response) will then be randomly assigned on a double-blind basis to one of two 24-month treatments (n=70-80/cell): 1) citalopram + donepezil/clinical management; or 2) CIT+placebo/clinical management. Randomization will be stratified by the presence/absence of Mild Cognitive Impairment. Depressed subjects will undergo repeated assessment of cognitive and functional status after response to antidepressant treatment (T1) and after three (T2), twelve (T3), and 24 months (T4) of maintenance treatment with either (CIT + DON) or (CIT + PBO). Subjects will exit the study if they demonstrate: (a) failure to respond to initial antidepressant pharmacotherapy; (b) recurrence of a major depressive episode during maintenance; or (c) dementia. Non-depressed control subjects (n=50) will participate in an identical schedule of assessments to provide a bench mark for interpreting both cognitive and functional trajectories seen in depressed subjects. The MTLD-III study will be the first controlled, long-term evaluation of strategies for improving and maintaining cognitive and functional competence in late-life depression. Testing ways of "staying well, staying sharp" is the objective of the MTLD-III protocol. The application has been amended (A1). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF CHOLINESTERASE INHIBITORS ON BETAAMYLOID Principal Investigator & Institution: Lahiri, Debomoy K.; Professor; Psychiatry; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007
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Summary: Alzheimer's disease (AD) is characterized by the severe loss of cholinergic neurons and depositions of amyloid beta peptide (Abeta). Three FDA- approved drugs (tacrine, donepezil and rivastigmine) for treating AD subjects belong to the category of cholinesterase (ChE) inhibitor (ChEI), which works by increasing the brain's supply of acetylcholine, a nerve communication chemical that is deficient in AD. These drugs are approved for treatment of mild to moderate AD and may not be as useful in more advanced stages. Our goal is to study the mechanism of ChEI drugs on amyloidogenic pathways that process beta-amyloid precursor protein (APP) to potentially neurotoxic Abeta. Such study is significant as there is increasing evidence that Abeta plays an important role in AD pathogenesis. This proposal is based on our discovery that treating cultured cells with certain ChEIs, such as tacrine and phenserine, significantly reduced levels of secreted APP (sAPP) and Abeta and may serve to slow the progression of AD as well as improve cognition. Notably, the mechanism of reduction of Abeta did not increase known alternative processing pathways and may therefore be less damaging. We are interested in identification of the mechanisms by which ChEIs block Abeta secretion to take advantage of the Abeta lowering property in developing novel therapeutic agents. SPEC. AIMS: The specific aims are: 1. To study the effects of acetylChEI (AChEI) and butyrl-ChEI (BchEI) on sAPP and Abeta levels. To examine the specificity of their actions, effects of i) AchEI (e.g., pheneserine) ii)BChEI (e.g. cymserine), and iii) compounds that are tacrine-derivatives (e.g. velnacrine) will be tested to identify structural aspects that lower Abeta. 2. To investigate the role of ChEIs on APP metabolism. Effects of ChEIs on i)APP processing in FAD-APP mutant cell lines and ii) the fate of APP carboxyl-truncated fragments will be tested. 3. To determine the possible targets of the drugs. Effects of ChEIs on the i) APP-cleaving enzyme (BACE), ii) 5' -untranslated region and iii) inhibition of Abeta levels in transgenic mice model of AD. We will mechanically select ChEIs that interact with the peripheral allosteric binding domain of ChEenzyme, or with the esteractic and anionic binding domains (phenserine and cymserine) and test it in APP/PS1 double transgenic mice. These results will indicate a unique effect of ChEIs on APP processing, which is independent of their selectivity for the enzyme. This property will be further investigated to maximize their potential effects in decreasing amyloid depositions, and which can be utilized to design better drugs for the treatment of AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODELING PHARMACOLOGICAL TREATMENTS IN THE TS65DN MOUSE Principal Investigator & Institution: Moran, Timothy H.; Paul R. Mchugh Professor & Vice Chair; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: The development of mouse models of Down Syndrome, with appropriate gene expression to mimic what takes place with a trisomy of human chromosome 21, provides test systems for potential therapeutic interventions aimed at improving cognitive performance. As detailed under Dr. Davisson's Project, the Ts65Dn mouse containing homologs to the majority of the genes on human chromosome 21. This segmental trisomy model has a number of distinct advantages over previous models, not the least of which is survival to adulthood. We and others have demonstrative a cognitive phenotype in the Ts65Dn mouse which has clear similarities to that seen in Down Syndrome. Ts65Dn mice demonstrate performance deficits in tests of learning and memory against a background of relatively intact motor and sensory abilities. Both acetylcholine and glutamate play important roles in learning and memory and are
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involved in neural organization during development. Alterations of cholinergic and glutamatergic activity in DS have been identified. The proposed experiments will 1) provide a more complete characterization of the development of cholinergic and glutamatergic systems in Ts65Dn mice. This characterization will provide a necessary background for proposed experiments aimed at, 2) assessing whether strategies aimed at blocking cholinergic degradation with the acetyl cholinesterase at, 2) assessing whether strategies aimed at blocking cholinergic degradation with the acetyl cholinesterase inhibitor donepezil or producing a development increase in cholinergic function with prenatal choline can improve performance in the Ts65Dn mouse, 3) assessing whether developmental treatment with piracetan alone, or piracetam combined with prenatal choline administration, improves performance in the Ts65Dn, and 4) assessing wheth4r developmental treatment with the neuroprotective agent acetyl-L-carnitine prevents cholinergic degeneration and results in improved cognitive performance in the Ts65Dn mouse. In these studies, we will assess performance in the Morris water maze and a cued and contextual conditioning paradigm. We will also monitor activity over the 24 hour cycle and in elevated plus maze paradigm. Behavioral assessments will be followed up by appropriate neurobiological analyses to determine whether the neurochemical systems impacted by these treatments respond similar in Ts65Dn and control mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NATURAL HISTORY, SEARCH FOR A MARKER AND THERAPY Principal Investigator & Institution: Sakkubai, Naidu; Kennedy Krieger Research Institute, Inc. Baltimore, Md 21205 Timing: Fiscal Year 2002 Summary: The goal of this project is to define the natural history, identify a diagnostic marker, understand the mechanism of neuronal dysfunction, and apply specific therapies early in the evolution of the disease to improve neurological status in Rett syndrome (RS). Based on the postulate that RS is a disorder of early brain growth, AIM 1 focuses on the identification of younger patients and delineation of early clinical features. Familial cases and their pedigrees will be documented in search of a genetic abnormality. Cases identified in Aim 1 will be a vital resource for all projects. In Aim 2 gene(s) defective in RS will be sought by classical cytogenetic approaches, and by representational difference analysis (RDA). Aim 2 will also search for proteins, and expressed genes that have up- or down regulated in RS, which may serve as a molecular fingerprint for the disease. Aim 3 is designed to study olfactory receptor neurons (ORNs) obtained from biopsies of olfactory neuroepithelium in RS girls, and compared to ORNs from normal and disease controls. A cell culture approach will provide direct access to RS neurons early in the course of the disease, and permit study of the evolution of neuronal defects in this disorder. In Aim 4 therapeutic interventions will attempt to prevent the devastating consequences of increased glutamate NMDA, and AMPA receptor induced neuronal injury by specific treatments with receptor antagonists, dextromethorphan and topiramate. To compensate for the significant reductions in choline acetyltransferase levels, treatment with an acetylcholine esterase inhibitordonepezil hydrochloride- to improve cognition will be tested. Efficacy of treatment will be monitored by clinical and neuroimaging techniques. Careful study of the nutritional status, and the role of dysphagia in growth failure will be examined in the light of therapeutic interventions. Use of growth factors or gene therapy will be considered when efficacy is established in the animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEW COGNITIVE TREATMENT FOR EARLY ALZHEIMER'S DISEASE Principal Investigator & Institution: Loewenstein, David A.; Professor; Psychiatry and Behavioral Scis; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: (from the application): Cognitive Rehabilitation has been shown to be effective in treating a variety of neurological disorders including traumatic brain injury and stroke. Until recently, there has been a paucity of research investigating the utility of this therapeutic modality with mildly impaired AD patients because of the assumption that any gains would be offset by progressive deterioration associated with the degenerative disease process. There is, however, data that suggest that techniques such as spaced retrieval" and other techniques which rely on procedural knowledge and implicit memory, motor learning and the provision of cognitive support at both encoding and retrieval of information can be beneficial to mildly impaired AD patients. The recently introduced cholinesterase inhibitors such as Donepezil (Aricept) have been empirically shown to slow the cognitive progression of AD to the point that they may enhance the efficacy of cognitive rehabilitation interventions when introduced early in the course of the illness. The potential synergistic effects of combined cognitive rehabilitation with pharmacological agents in AD is exciting, given the promise of newer and more effective pharmacological agents for this condition in the future. This has important implications for optimizing and maintaining the patient's cognitive and functional independence for the longest period of time. The proposed study is an evaluation of a new systematic cognitive retraining program for enhancing and maintaining the cognitive and functional status of AD patients receiving a cholinesterase inhibitor (Donepezil). In addition to its state of the-art cognitive approaches, the present theory-driven paradigm is unique in two other ways: its incorporation of a strong functional component and its use of the primary caregiver as a therapy extender to promote generalization and maintenance of gains attained in the clinical setting to the patient's everyday life. While prior efforts have included one or two of these elements in isolation, no previous program has offered this type of integrated approach in the treatment of AD among individuals who are receiving an effective pharmacological agent. In addition to the direct benefit to AD patients, the proposed cognitive rehabilitation intervention is also expected to reduce the caregiver's perceived burden and psychological distress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSIOLOGY OF CHOLINERGIC BASAL FOREBRAIN NEURONS Principal Investigator & Institution: Griffith, William H.; Professor; Medical Pharmacology & Toxicology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2003; Project Start 01-JAN-1989; Project End 31-AUG-2008 Summary: (provided by applicant): Disruption of neuronal calcium (Ca2+) homeostasis is associated with aging and cognitive decline in humans and animal models. However, cognitive impairment is variable in the aging population and certain neuronal cell-types are more susceptible to age-related changes than others. In humans, cholinergic neurons in the basal forebrain are preferentially affected by age-related dysfunction, including Alzheimer's disease. In rats, cholinergic dysfunction in the basal forebrain has been associated with cognitive impairment, but the cellular and molecular mechanisms that mediate cognitive dysfunction are largely unknown. Our lab has described age-related
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differences in gene expression and functional physiology of neurons from the rat medial septum and nucleus of the diagonal band (MS/nDB). To understand the cellular and molecular mechanisms responsible for age-related cognitive impairment, we need to define cell-type specific patterns of neuronal physiology/molecular biology relevant to cognitive decline in an aging model. We hypothesize that age-related changes in Ca2+ homeostatic function differentially affect specific subtypes of cholinergic neurons and that the initiation of these changes precipitates a cognitive decline that can be reversed or prevented by appropriate pharmacology. To investigate this, we will measure mRNA expression in acutely dissociated MS/nDB neurons from Fischer 344 rats of different ages (young, 1-4 months; middle, 12-16 months; aged, 24-26 months) using real-time fluorescent detection PCR to quantitate expression and identify cell-types. Molecular descriptions will be combined with functional assays of voltage-gated Ca2+ channels, Ca2+ homeostasis and mitochondria using patch-clamp electrophysiology, Ca2+ sensitive ratiometric microfluorimetry, laser scanning confocal microscopy and electron microscopy. Each rat will be behaviorally characterized as cognitively impaired or nonimpaired in a spatial memory test relevant to the basal forebrain cholinergic system (Morris water maze), allowing us to associate cellular results with cognitive status. We will define at least three functional and molecular properties from each animal. Finally, we will treat rats with donepezil (cholinesterase inhibitor) or nimodipine (Ca2+ channel blocker) to reverse age-related behavioral impairments and physiological changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPEUTIC CORRELATES OF ACHE PET IMAGING IN DEMENTIA Principal Investigator & Institution: Bohnen, Nicolas; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: Despite the widespread use of one acetylcholinesterase-inhibitor (AChE- I), donepezil, for treating cognitive deficits of Alzheimer's disease (AD), the efficacy of this and other AChE-I drugs has been modest, and highly variable. As most clinical trials of AChE-I agents have focused on gaining regulatory approval, little is known about what clinical symptoms in AD respond best to AChE-I therapy agents have focused on gaining regulatory approval, little is known about what clinical symptoms in AD respond best to AChE-I therapy. Preliminary work suggests that the primary cognitive effect of AChE-I therapy is on attention, rather than short-term memory, and there is burgeoning evidence that various non- cognitive symptoms in AD patients, particularly apathy, may also benefit from AChE-I therapy. Functions of attention and apathy have been shown to be functionally related to the prefrontal cortex. The aim of this study is to examine the degree to which cerebral cholinergic deficits, as measured by in vivo AChE binding activity using PET neuroimaging, are associated with clinical responsivity to AChE-I therapy. AChE PET imaging is a novel approach to s to the study of acetylcholine in the living. This study, to be hypothesis that AD patients have lower global cortical AChE binding activity compared to normal control subjects. In addition, we will examine the second hypothesis that specific symptom manifestations (i.e. attentional deficits and apathy) across AC patients may be a robust marker of regional (prefrontal) decreases in AChE activity, and associated with greater responses to donepezil in a 12 week open-label trial. The over-arching goal of this study is to evaluate clinical therapeutic challenge in conjunction with in vivo marker of AChE activity before and after donepezil treatment to identify specific clinical identifications
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for the use of AChE-I therapy. We will also study cerebral glucose metabolism before and after donepezil treatment in a subset of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATING DEMENTIA/PARKINSONISM
AGITATION/PSYCHOSIS
IN
Principal Investigator & Institution: Kurlan, Roger M.; Professor; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2005 Summary: Psychosis and agitation often occur in the course of dementia and are a major source of patient disability and caregiver stress. For the common situation in which extrapyramidal (parkinsonian) motor dysfunction accompanies dementia, there is a therapeutic dilemma since the most frequently used drugs to treat the behavioral problems, neuroleptic antipsychotics, can worsen parkinsonism and have been associated with severe extrapyramidal reactions in some types of dementia. To date, the efficacy and tolerability of the most promising alternative medications to treat psychosis and agitation, namely atypical antipsychotics and cholinesterase inhibitors, have not been tested in patients with a primary dementia selected for coexisting parkinsonism. Furthermore, no study has examined the possible additive benefits or risks of these 2 drug classes when used in combination. Proposed is a multicenter (20 member sites of the Alzheimer's Disease Cooperative Study [ADCS]), randomized, controlled clinical trial in which 120 subjects with a primary dementia (probable Alzheimer's disease [AD] or probable dementia with Lewy bodies [DLB]) and coexisting parkinsonism will be randomized according to a 2 X 2 factorial design to 1 of 4 treatments: quetiapine (QUET; an atypical antipsychotic with a favorable extrapyramidal side effect profile), donepezil (a cholinesterase inhibitor), the combination of QUET + DONEP, or placebo. Each subject participates in the trial for 10 weeks and systematic ratings of behavior, motor function, cognition, adverse events and other outcomes occur at baseline and after 6 and 10 weeks of assigned treatment. This study will provide important information regarding the optimal treatment of psychosis and agitation for patients with the commonly encountered combination of primary dementia and parkinsonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRIAL OF VITAMIN E AND DONEPEZIL HCL TO DELAY CLINICAL PROGRESSION IN ALZHEIMER'S Principal Investigator & Institution: Adair, John; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VITAMIN E & DONEPEZIL (ARICEPT) IN ALZHEIMER'S Principal Investigator & Institution: Growdon, John H.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VITAMIN E AND DONEPEZIL HCL (ARICEPT) TO DELAY PROGRESSION TO ALZHEIMER'S DISEASE Principal Investigator & Institution: Mesulam, Marek-Marsel M.; Director; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “donepezil” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for donepezil in the PubMed Central database: •
Purpuric rash with donepezil treatment. by Bryant CA, Ouldred E, Jackson SH.; 1998 Sep 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28670
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 donepezil, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “donepezil” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for donepezil (hyperlinks lead to article summaries):
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 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 12-week, open trial of donepezil hydrochloride in patients with multiple sclerosis and associated cognitive impairments. Author(s): Greene YM, Tariot PN, Wishart H, Cox C, Holt CJ, Schwid S, Noviasky J. Source: Journal of Clinical Psychopharmacology. 2000 June; 20(3): 350-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10831023
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A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Author(s): Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, Pratt RD; “312” Study Group. Source: Neurology. 2001 August 14; 57(3): 481-8. Erratum In: Neurology 2001 November 27; 57(10): 1942. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502917
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A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Author(s): Deleu D. Source: Neurology. 2002 March 12; 58(5): 835-6; Author Reply 836. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889261
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A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Author(s): Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P; Donepezil Nordic Study Group. Source: Neurology. 2001 August 14; 57(3): 489-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502918
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A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Author(s): Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT. Source: Neurology. 1998 January; 50(1): 136-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9443470
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A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. Author(s): Prasher VP, Huxley A, Haque MS; Down syndrome Ageing Study Group. Source: International Journal of Geriatric Psychiatry. 2002 March; 17(3): 270-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11921156
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A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease. Author(s): Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E; Donepezil MSAD Study Investigators Group. Source: Neurology. 2001 August 28; 57(4): 613-20. Erratum In: Neurology 2001 December 11; 57(11): 2153. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11524468
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A case of Korsakoff's syndrome improved by high doses of donepezil. Author(s): Iga JI, Araki M, Ishimoto Y, Ohmori T. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2001 November-December; 36(6): 553-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704621
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A case series of D-cycloserine added to donepezil in the treatment of Alzheimer's disease. Author(s): Falk WE, Daly EJ, Tsai GE, Gunther J, Brown P. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Fall; 14(4): 466-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426422
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A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066. Author(s): Snape MF, Misra A, Murray TK, De Souza RJ, Williams JL, Cross AJ, Green AR. Source: Neuropharmacology. 1999 January; 38(1): 181-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10193909
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A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia. Author(s): Friedman JI, Adler DN, Howanitz E, Harvey PD, Brenner G, Temporini H, White L, Parrella M, Davis KL. Source: Biological Psychiatry. 2002 March 1; 51(5): 349-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904128
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A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates. Author(s): Risch SC, McGurk S, Horner MD, Nahas Z, Owens SD, Molloy M, Gilliard C, Christie S, Markowitz JS, DeVane CL, Mintzer J, George MS. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2001; 7(2): 105-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320158
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A large, community-based, open-label trial of donepezil in the treatment of Alzheimer's disease. Author(s): Relkin NR, Reichman WE, Orazem J, McRae T. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(1): 15-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714795
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A long-term comparison of galantamine and donepezil in the treatment of Alzheimer's disease. Author(s): Wilcock G, Howe I, Coles H, Lilienfeld S, Truyen L, Zhu Y, Bullock R, Kershaw P; GAL-GBR-2 Study Group. Source: Drugs & Aging. 2003; 20(10): 777-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875613
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A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer's disease. Author(s): Jones RW, Soininen H, Hager K, Aarsland D, Passmore P, Murthy A, Zhang R, Bahra R. Source: International Journal of Geriatric Psychiatry. 2004 January; 19(1): 58-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716700
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A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease. Author(s): Wilkinson DG, Passmore AP, Bullock R, Hopker SW, Smith R, Potocnik FC, Maud CM, Engelbrecht I, Hock C, Ieni JR, Bahra RS. Source: Int J Clin Pract. 2002 July-August; 56(6): 441-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166542
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A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. Author(s): Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, Whalen E. Source: Journal of the American Geriatrics Society. 2001 December; 49(12): 1590-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843990
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A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil. Author(s): Finkel SI, Mintzer JE, Dysken M, Krishnan KR, Burt T, McRae T. Source: International Journal of Geriatric Psychiatry. 2004 January; 19(1): 9-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716694
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A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder. Author(s): Hardan AY, Handen BL. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Fall; 12(3): 237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12427297
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Abnormal movements with donepezil in Alzheimer disease. Author(s): Amouyal-Barkate K, Bagheri-Charabiani H, Montastruc JL, Moulias S, Vellas B. Source: The Annals of Pharmacotherapy. 2000 November; 34(11): 1347. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11098352
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Acetylcholinesterase inhibitor (donepezil hydrochloride) reduces heart rate variability. Author(s): Masuda Y, Kawamura A. Source: Journal of Cardiovascular Pharmacology. 2003 January; 41 Suppl 1: S67-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688400
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Adjunctive donepezil in attention deficit hyperactivity disorder youth: case series. Author(s): Wilens TE, Biederman J, Wong J, Spencer TJ, Prince JB. Source: Journal of Child and Adolescent Psychopharmacology. 2000 Fall; 10(3): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11052411
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Adverse effects associated with the use of donepezil in general practice in England. Author(s): Dunn NR, Pearce GL, Shakir SA. Source: Journal of Psychopharmacology (Oxford, England). 2000; 14(4): 406-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11198060
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Adverse effects of donepezil in treating Alzheimer's disease associated with Down's syndrome. Author(s): Hemingway-Eltomey JM, Lerner AJ. Source: The American Journal of Psychiatry. 1999 September; 156(9): 1470. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10484967
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Advertisements for donepezil (Aricept) in the BMJ. Advertisement suggests an unrealistic improvement in mental status. Author(s): Gray S. Source: Bmj (Clinical Research Ed.). 1997 May 24; 314(7093): 1555. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9183222
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Advertisements for donepezil (Aricept) in the BMJ. Local committee has declined to approve NHS hospital prescription of donepezil. Author(s): Wagner N. Source: Bmj (Clinical Research Ed.). 1997 May 24; 314(7093): 1555-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9183223
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Advertisements for donepezil. BMJ should require advertisements to detail actual state of evidence. Author(s): Stein K, Milne R, Best L. Source: Bmj (Clinical Research Ed.). 1997 December 13; 315(7122): 1623-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437304
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Advertisements for donepezil. More convincing evidence of efficacy needs to be cited. Author(s): Greenhalgh T. Source: Bmj (Clinical Research Ed.). 1997 December 13; 315(7122): 1623; Author Reply 1624. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437303
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Advertisements for donepezil. National policy needs to be set for prescribing of this drug. Author(s): Boothby H, Zaidi SM, Seth V, Khalaf S, Jameel H, Mahomed S, al-Yassiri. Source: Bmj (Clinical Research Ed.). 1997 December 13; 315(7122): 1624. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437305
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Advertisements for donepezil. Prices charged for private prescriptions for donepezil show huge variation. Author(s): Jones RW, Mann JB, Saunders SA. Source: Bmj (Clinical Research Ed.). 1997 December 13; 315(7122): 1624. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437306
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Advertisements for donepezil. Review of drug in Drug and Therapeutics Bulletin is uninformed. Author(s): Wilkinson D. Source: Bmj (Clinical Research Ed.). 1997 December 13; 315(7122): 1625. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437307
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Aggressive behaviour associated with donepezil treatment: a case report. Author(s): Bianchetti A, Trabucchi M, Cipriani G. Source: International Journal of Geriatric Psychiatry. 2003 July; 18(7): 657-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12833312
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An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial. Author(s): Wimo A, Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm AL, Mastey V, Haglund A, Zhang R, Miceli R, Chin W, Subbiah P; Donepezil Nordic Study Group. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(1): 44-54. Erratum In: Dement Geriatr Cogn Disord. 2003; 16(2): 102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457078
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An economic evaluation of donepezil in the treatment of Alzheimer's disease. Author(s): Small GW, Donohue JA, Brooks RL. Source: Clinical Therapeutics. 1998 July-August; 20(4): 838-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9737841
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An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function. Author(s): Tiseo PJ, Vargas R, Perdomo CA, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 51-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839767
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An evaluation of the pharmacokinetics of donepezil HCl in patients with moderately to severely impaired renal function. Author(s): Tiseo PJ, Foley K, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 56-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839768
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An N-of-1 randomized controlled trial ('N-of-1 trial') of donepezil in the treatment of non-progressive amnestic syndrome. Author(s): Price JD, Grimley Evans J. Source: Age and Ageing. 2002 July; 31(4): 307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147570
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An observational clinical study of the efficacy and tolerability of donepezil in the treatment of Alzheimer's disease. Author(s): Hager K, Calabrese P, Frolich L, Gobel C, Berger FM. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(4): 189-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626851
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An open-label trial of donepezil (aricept) in the treatment of persons with mild traumatic brain injury. Author(s): Kaye NS, Townsend JB 3rd, Ivins R. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 383-4; Author Reply 384-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928519
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An open-labeled trial of adjunctive donepezil for cognitive impairments in patients with schizophrenia. Author(s): Buchanan RW, Summerfelt A, Tek C, Gold J. Source: Schizophrenia Research. 2003 January 1; 59(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413639
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ApoE genotype influences the biological effect of donepezil on APP metabolism in Alzheimer disease: evidence from a peripheral model. Author(s): Borroni B, Colciaghi F, Pastorino L, Archetti S, Corsini P, Cattabeni F, Di Luca M, Padovani A. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 June; 12(3): 195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12007670
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Atrophy of the substantia innominata on magnetic resonance imaging and response to donepezil treatment in Alzheimer's disease. Author(s): Hanyu H, Tanaka Y, Sakurai H, Takasaki M, Abe K. Source: Neuroscience Letters. 2002 February 8; 319(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814647
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Atrophy of the substantia innominata on magnetic resonance imaging predicts response to donepezil treatment in Alzheimer's disease patients. Author(s): Tanaka Y, Hanyu H, Sakurai H, Takasaki M, Abe K. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(3): 119-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826736
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Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study. Author(s): Nahas Z, George MS, Horner MD, Markowitz JS, Li X, Lorberbaum JP, Owens SD, McGurk S, DeVane L, Risch SC. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2003 June; 9(3): 274-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925933
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Behavioral complications associated with donepezil. Author(s): Wengel SP, Roccaforte WH, Burke WJ, Bayer BL, McNeilly DP, Knop D. Source: The American Journal of Psychiatry. 1998 November; 155(11): 1632-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9812142
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Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia. Author(s): Stryjer R, Strous RD, Bar F, Werber E, Shaked G, Buhiri Y, Kotler M, Weizman A, Rabey JM. Source: Clinical Neuropharmacology. 2003 January-February; 26(1): 12-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567159
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Beneficial effect of donepezil on sensorimotor function after stroke. Author(s): Berthier ML, Pujol J, Gironell A, Kulisevsky J, Deus J, Hinojosa J, Soriano-Mas C. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 September; 82(9): 725-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960916
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Better cognitive and psychopathologic response to donepezil in patients prospectively diagnosed as dementia with Lewy bodies: a preliminary study. Author(s): Samuel W, Caligiuri M, Galasko D, Lacro J, Marini M, McClure FS, Warren K, Jeste DV. Source: International Journal of Geriatric Psychiatry. 2000 September; 15(9): 794-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984725
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Brain injury, cognitive impairment, and donepezil. Author(s): Whitlock JA Jr. Source: The Journal of Head Trauma Rehabilitation. 1999 August; 14(4): 424-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10407214
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Can donepezil be considered a mild antipsychotic in dementia treatment? A report of donepezil use in 6 patients. Author(s): Terao T, Shimomura T, Nakamura J. Source: The Journal of Clinical Psychiatry. 2003 November; 64(11): 1392-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14658957
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Cardiovascular effects of donepezil in patients with dementia. Author(s): McLaren AT, Allen J, Murray A, Ballard CG, Kenny RA. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(4): 183-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626850
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Carers' assessment of patients on donepezil--how reliable? Author(s): Allington M, Salib E. Source: International Journal of Geriatric Psychiatry. 2000 December; 15(12): 1155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180476
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Cerebrospinal fluid acetylcholinesterase activity after long-term treatment with donepezil and rivastigmina. Author(s): Amici S, Lanari A, Romani R, Antognelli C, Gallai V, Parnetti L. Source: Mechanisms of Ageing and Development. 2001 November; 122(16): 2057-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589922
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Changes in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy. Author(s): Staff RT, Gemmell HG, Shanks MF, Murray AD, Venneri A. Source: Nuclear Medicine Communications. 2000 January; 21(1): 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10717900
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Cholinergic modulation of speed of early information processing: the effect of donepezil on inspection time. Author(s): Hutchison CW, Nathan PJ, Mrazek L, Stough C. Source: Psychopharmacology. 2001 June; 155(4): 440-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441435
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Cholinesterase inhibitors in Alzheimer's disease: donepezil or rivastigmine? Author(s): Sharma JC. Source: Int J Clin Pract. 2002 July-August; 56(6): 414-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166537
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Chronic donepezil treatment is associated with slowed cognitive decline in Alzheimer's disease. Author(s): Doody RS, Dunn JK, Clark CM, Farlow M, Foster NL, Liao T, Gonzales N, Lai E, Massman P. Source: Dementia and Geriatric Cognitive Disorders. 2001 July-August; 12(4): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11351141
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Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review. Author(s): Clegg A, Bryant J, Nicholson T, McIntyre L, De Broe S, Gerard K, Waugh N. Source: Health Technology Assessment (Winchester, England). 2001; 5(1): 1-137. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11262420
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Clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for Alzheimer's disease. A systematic review. Author(s): Clegg A, Bryant J, Nicholson T, McIntyre L, De Broe S, Gerard K, Waugh N. Source: International Journal of Technology Assessment in Health Care. 2002 Summer; 18(3): 497-507. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12391943
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Clinical efficacy and safety of donepezil on cognitive and global function in patients with Alzheimer's disease. A 24-week, multicenter, double-blind, placebo-controlled study in Japan. E2020 Study Group. Author(s): Homma A, Takeda M, Imai Y, Udaka F, Hasegawa K, Kameyama M, Nishimura T. Source: Dementia and Geriatric Cognitive Disorders. 2000 November-December; 11(6): 299-313. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044775
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Clinical experience with Donepezil (Aricept) in the UK. Author(s): Wilkinson D. Source: Journal of Neural Transmission. Supplementum. 1998; 54: 311-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9850940
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Clinical profile of donepezil in the treatment of Alzheimer's disease. Author(s): Doody RS. Source: Gerontology. 1999; 45 Suppl 1: 23-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876215
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Combination of donepezil and gabapentin for behavioral disorders in Alzheimer's disease. Author(s): Dallocchio C, Buffa C, Mazzarello P. Source: The Journal of Clinical Psychiatry. 2000 January; 61(1): 64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695652
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Combination of risperidone and donepezil in Lewy body dementia. Author(s): Geizer M, Ancill RJ. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1998 May; 43(4): 421-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9598283
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Combination therapy of donepezil and vitamin E in Alzheimer disease. Author(s): Klatte ET, Scharre DW, Nagaraja HN, Davis RA, Beversdorf DQ. Source: Alzheimer Disease and Associated Disorders. 2003 April-June; 17(2): 113-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794389
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Comments on donepezil open label trial. Author(s): Charlesworth G, Shepstone L. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1999 September; 9(5): 441-2. Erratum In: Eur Neuropsychopharmacol 2000 March; 10(2): 143. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10523051
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Comments on Efficacy and safety of rivastigmine in patients with Alzheimer's disease who failed to benefit from treatment with donepezil. Author(s): McRae TD, Schwam EM. Source: Current Medical Research and Opinion. 2002; 18(6): I-Iii; Author Reply Iv-Vi. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442885
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Comparative study of donepezil and rivastigmine. Author(s): Gray R. Source: Int J Clin Pract. 2003 June; 57(5): 449; Author Reply 449. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846358
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Comparative study of donepezil and rivastigmine. Author(s): Grossberg G. Source: Int J Clin Pract. 2003 January-February; 57(1): 70-1; Author Reply 71. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587950
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Comparison of functional and cognitive donepezil effects in Alzheimer's disease. Author(s): Saine K, Cullum CM, Martin-Cook K, Hynan L, Svetlik DA, Weiner MF. Source: Int Psychogeriatr. 2002 June; 14(2): 181-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243208
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Concurrent administration of donepezil HCl and cimetidine: assessment of pharmacokinetic changes following single and multiple doses. Author(s): Tiseo PJ, Perdomo CA, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 25-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839762
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Concurrent administration of donepezil HCl and digoxin: assessment of pharmacokinetic changes. Author(s): Tiseo PJ, Perdomo CA, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 40-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839765
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Concurrent administration of donepezil HCl and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses. Author(s): Tiseo PJ, Perdomo CA, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 30-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839763
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Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple-dose administration in healthy volunteers. Author(s): Tiseo PJ, Foley K, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 35-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839764
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Convulsions induced by donepezil. Author(s): Babic T, Zurak N. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 March; 66(3): 410. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084551
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Correlation of the intrinsic clearance of donepezil (Aricept) between in vivo and in vitro studies in rat, dog and human. Author(s): Matsui K, Taniguchi S, Yoshimura T. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1999 November; 29(11): 1059-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598742
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Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer's disease. Author(s): Neumann PJ, Hermann RC, Kuntz KM, Araki SS, Duff SB, Leon J, Berenbaum PA, Goldman PA, Williams LW, Weinstein MC. Source: Neurology. 1999 April 12; 52(6): 1138-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10214734
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Co-use of donepezil and hypnotics among Alzheimer's disease patients living in the community. Author(s): Stahl SM, Markowitz JS, Gutterman EM, Papadopoulos G. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 466-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716251
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Defining meaningful change in Alzheimer's disease trials: the donepezil experience. Author(s): McLendon BM, Doraiswamy PM. Source: Journal of Geriatric Psychiatry and Neurology. 1999 Spring; 12(1): 39-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10447153
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Delirium caused by donepezil: a case study. Author(s): Kawashima T, Yamada S. Source: The Journal of Clinical Psychiatry. 2002 March; 63(3): 250-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926729
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Dementia with Lewy bodies: response of delirium-like features to donepezil. Author(s): Kaufer DI, Catt KE, Lopez OL, DeKosky ST. Source: Neurology. 1998 November; 51(5): 1512. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9818904
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Determination of donepezil, an acetylcholinesterase inhibitor, in human plasma by high-performance liquid chromatography with ultraviolet absorbance detection. Author(s): Yasui-Furukori N, Furuya R, Takahata T, Tateishi T. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 March 5; 768(2): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888054
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Discontinuation syndrome following donepezil cessation. Author(s): Singh S, Dudley C. Source: International Journal of Geriatric Psychiatry. 2003 April; 18(4): 282-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673601
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Do you know about donepezil and succinylcholine? Author(s): Walker C, Perks D. Source: Anaesthesia. 2002 October; 57(10): 1041. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358980
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Donepezil (Aricept) therapy for Alzheimer's disease. Author(s): Geldmacher DS. Source: Compr Ther. 1997 July; 23(7): 492-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9262925
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Donepezil and Alzheimer's dementia. Author(s): Earl-Slater A, Walley T. Source: Clinical Performance and Quality Health Care. 2000; 8(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11183967
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Donepezil and athetosis in an elderly patient with Alzheimer's disease. Author(s): Tanaka M, Yokode M, Kita T, Matsubayashi K. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 889-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757588
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Donepezil and flight simulator performance: effects on retention of complex skills. Author(s): Connemann BJ. Source: Neurology. 2003 September 9; 61(5): 721; Author Reply 721. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963782
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Donepezil and flight simulator performance: effects on retention of complex skills. Author(s): Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O'Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ. Source: Neurology. 2002 July 9; 59(1): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12105320
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Donepezil and paroxetine: possible drug interaction. Author(s): Carrier L. Source: Journal of the American Geriatrics Society. 1999 August; 47(8): 1037. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10443872
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Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents. Author(s): Burt T. Source: Current Psychiatry Reports. 2000 December; 2(6): 473-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11122998
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Donepezil and rivastigmine in the treatment of Alzheimer's disease: a best-evidence synthesis of the published data on their efficacy and cost-effectiveness. Author(s): Wolfson C, Oremus M, Shukla V, Momoli F, Demers L, Perrault A, Moride Y. Source: Clinical Therapeutics. 2002 June; 24(6): 862-86; Discussion 837. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117079
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Donepezil and succinylcholine. Author(s): Heath ML. Source: Anaesthesia. 2003 February; 58(2): 202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562439
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Donepezil as add-on treatment of psychotic symptoms in patients with dementia of the Alzheimer's type. Author(s): Bergman J, Brettholz I, Shneidman M, Lerner V. Source: Clinical Neuropharmacology. 2003 March-April; 26(2): 88-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671528
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Donepezil dose-dependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzymepositive structures in the human and rat brain. Author(s): Kasa P, Papp H, Kasa P Jr, Torok I. Source: Neuroscience. 2000; 101(1): 89-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11068139
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Donepezil for Alzheimer's disease. Author(s): Sparano N. Source: The Journal of Family Practice. 1998 May; 46(5): 356. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9597987
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Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical profiles. Author(s): Shigeta M, Homma A. Source: Cns Drug Rev. 2001 Winter; 7(4): 353-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11830754
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Donepezil for anticholinergic drug intoxication: a case report. Author(s): Noyan MA, Elbi H, Aksu H. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 August; 27(5): 885-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921925
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Donepezil for behavioural disorders associated with Lewy bodies: a case series. Author(s): Lanctot KL, Herrmann N. Source: International Journal of Geriatric Psychiatry. 2000 April; 15(4): 338-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10767734
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Donepezil for cognitive deficits following traumatic brain injury: a case report. Author(s): Bourgeois JA, Bahadur N, Minjares S. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Fall; 14(4): 463-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426418
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Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study. Author(s): Aarsland D, Laake K, Larsen JP, Janvin C. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 June; 72(6): 708-12. Erratum In: J Neurol Neurosurg Psychiatry 2002 September; 73(3): 354. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023410
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Donepezil for cognitive impairment in Parkinson's disease: a randomized controlled trial. Author(s): Marder K. Source: Curr Neurol Neurosci Rep. 2002 September; 2(5): 390-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169217
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Donepezil for dementia due to Alzheimer's disease. Author(s): Birks JS, Harvey R. Source: Cochrane Database Syst Rev. 2003; (3): Cd001190. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917900
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Donepezil for dementia with Lewy bodies: a case study. Author(s): Aarsland D, Bronnick K, Karlsen K. Source: International Journal of Geriatric Psychiatry. 1999 January; 14(1): 69-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10029938
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Donepezil for Down's syndrome. Author(s): Kishnani PS, Spiridigliozzi GA, Heller JH, Sullivan JA, Doraiswamy PM, Krishnan KR. Source: The American Journal of Psychiatry. 2001 January; 158(1): 143. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11136652
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Donepezil for Huntington's disease. Author(s): Fernandez HH, Friedman JH, Grace J, Beason-Hazen S. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2000 January; 15(1): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10634264
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Donepezil for memory dysfunction in schizophrenia. Author(s): Howard AK, Thornton AE, Altman S, Honer WG. Source: Journal of Psychopharmacology (Oxford, England). 2002 September; 16(3): 26770. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12236636
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Donepezil for mild and moderate Alzheimer's disease. Author(s): Birks JS, Melzer D, Beppu H. Source: Cochrane Database Syst Rev. 2000; (4): Cd001190. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034704
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Donepezil for mild and moderate Alzheimer's disease. Author(s): Birks J S, Melzer D. Source: Cochrane Database Syst Rev. 2000; (2): Cd001190. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796620
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Donepezil for nursing home patients with dementia: a reinterpretation of the evidence. Author(s): Steinman MA, Covinsky KE. Source: Journal of the American Geriatrics Society. 2003 January; 51(1): 132; Author Reply 132-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534859
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Donepezil for postoperative delirium associated with Alzheimer's disease. Author(s): Wengel SP, Burke WJ, Roccaforte WH. Source: Journal of the American Geriatrics Society. 1999 March; 47(3): 379-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078910
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Donepezil for postoperative delirium. Author(s): Gleason OC. Source: Psychosomatics. 2003 September-October; 44(5): 437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954923
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Donepezil for psychotropic-induced memory loss. Author(s): Jacobsen FM, Comas-Diaz L. Source: The Journal of Clinical Psychiatry. 1999 October; 60(10): 698-704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10549687
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Donepezil for the treatment of a schizophrenia patient with frontal lobotomy. Author(s): Mazeh D, Mirecki I, Paleacu D, Barak Y. Source: Journal of Clinical Psychopharmacology. 2003 October; 23(5): 522. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520133
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Donepezil for the treatment of behavioral symptoms in patients with Alzheimer's disease. Author(s): Paleacu D, Mazeh D, Mirecki I, Even M, Barak Y. Source: Clinical Neuropharmacology. 2002 November-December; 25(6): 313-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469005
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Donepezil for the treatment of language deficits in adults with Down syndrome: a preliminary 24-week open trial. Author(s): Heller JH, Spiridigliozzi GA, Sullivan JA, Doraiswamy PM, Krishnan RR, Kishnani PS. Source: American Journal of Medical Genetics. 2003 January 15; 116A(2): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494428
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Donepezil for the treatment of mild to moderate Alzheimer's disease in France: the economic implications. Author(s): Fagnani F, Lafuma A, Pechevis M, Rigaud AS, Traykov L, Seux ML, Forette F. Source: Dementia and Geriatric Cognitive Disorders. 2004; 17(1-2): 5-13. Epub 2003 October 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560059
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Donepezil for the treatment of psychosis in dementia with Lewy bodies. Author(s): Fergusson E, Howard R. Source: International Journal of Geriatric Psychiatry. 2000 March; 15(3): 280-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10713588
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Donepezil for Tourette's disorder and ADHD. Author(s): Hoopes SP. Source: Journal of Clinical Psychopharmacology. 1999 August; 19(4): 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10440471
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Donepezil for treatment of dementia with Lewy bodies: a case series of nine patients. Author(s): Shea C, MacKnight C, Rockwood K. Source: Int Psychogeriatr. 1998 September; 10(3): 229-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9785144
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Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study. Author(s): Tune L, Tiseo PJ, Ieni J, Perdomo C, Pratt RD, Votaw JR, Jewart RD, Hoffman JM. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2003 March-April; 11(2): 169-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611746
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Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Author(s): Sugimoto H, Yamanishi Y, Iimura Y, Kawakami Y. Source: Current Medicinal Chemistry. 2000 March; 7(3): 303-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10637367
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Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease. Author(s): Nakano S, Asada T, Matsuda H, Uno M, Takasaki M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 October; 42(10): 1441-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11585854
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Donepezil hydrochloride: a treatment drug for Alzheimer's disease. Author(s): Sugimoto H. Source: Chemical Record (New York, N.Y.). 2001; 1(1): 63-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893059
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Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Author(s): Rogers SL, Doody RS, Mohs RC, Friedhoff LT. Source: Archives of Internal Medicine. 1998 May 11; 158(9): 1021-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9588436
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Donepezil improves symptoms of delirium in dementia: implications for future research. Author(s): Wengel SP, Roccaforte WH, Burke WJ. Source: Journal of Geriatric Psychiatry and Neurology. 1998 Fall; 11(3): 159-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9894735
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Donepezil in a chronic drug user--a potential treatment? Author(s): Jovanovski D, Zakzanis KK. Source: Human Psychopharmacology. 2003 October; 18(7): 561-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533139
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Donepezil in advanced dementia, or delirium? Author(s): Palmer TR. Source: Journal of the American Medical Directors Association. 2004 January-February; 5(1): 67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726803
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Donepezil in Alzheimer's disease: eighteen month results from Southampton Memory Clinic. Author(s): Matthews HP, Korbey J, Wilkinson DG, Rowden J. Source: International Journal of Geriatric Psychiatry. 2000 August; 15(8): 713-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10960883
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Donepezil in schizophrenia--is it helpful? An experimental design case study. Author(s): MacEwan GW, Ehmann TS, Khanbhai I, Wrixon C. Source: Acta Psychiatrica Scandinavica. 2001 December; 104(6): 469-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782241
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Donepezil in the treatment of Alzheimer disease. Author(s): Deleu D, Hanssens Y. Source: Archives of Neurology. 2000 September; 57(9): 1380. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987910
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Donepezil in the treatment of Alzheimer's disease: long-term efficacy and safety. Author(s): Rocca P, Cocuzza E, Marchiaro L, Bogetto F. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 February; 26(2): 369-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817515
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Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Author(s): Whelan FJ, Walker MS, Schultz SK. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 2000 September; 12(3): 131-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984001
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Donepezil in the treatment of hallucinations and delusions in Parkinson's disease. Author(s): Fabbrini G, Barbanti P, Aurilia C, Pauletti C, Lenzi GL, Meco G. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 April; 23(1): 41-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111620
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Donepezil in the treatment of mild to moderate Alzheimer's disease: report of a Belgian multicenter study. Author(s): Santens P, Ventura M. Source: Acta Neurol Belg. 2003 September; 103(3): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14626696
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Donepezil in the treatment of opioid-induced sedation: report of six cases. Author(s): Slatkin NE, Rhiner M, Bolton TM. Source: Journal of Pain and Symptom Management. 2001 May; 21(5): 425-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11369163
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Donepezil in the treatment of progressive supranuclear palsy. Author(s): Fabbrini G, Barbanti P, Bonifati V, Colosimo C, Gasparini M, Vanacore N, Meco G. Source: Acta Neurologica Scandinavica. 2001 February; 103(2): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11227131
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Donepezil in treatment-resistant bipolar disorder. Author(s): Burt T, Sachs GS, Demopulos C. Source: Biological Psychiatry. 1999 April 15; 45(8): 959-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10386177
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Donepezil in vascular dementia: a randomized, placebo-controlled study. Author(s): Wilkinson D, Doody R, Helme R, Taubman K, Mintzer J, Kertesz A, Pratt RD; Donepezil 308 Study Group. Source: Neurology. 2003 August 26; 61(4): 479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12939421
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Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease. Author(s): Geldmacher DS, Provenzano G, McRae T, Mastey V, Ieni JR. Source: Journal of the American Geriatrics Society. 2003 July; 51(7): 937-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834513
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Donepezil management of schizophrenia with associated dementia. Author(s): Stryjer R, Bar F, Strous RD, Baruch Y, Rabey JM. Source: Journal of Clinical Psychopharmacology. 2002 April; 22(2): 226-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910273
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Donepezil medicated memory improvement in traumatic brain injury during post acute rehabilitation. Author(s): Taverni JP, Seliger G, Lichtman SW. Source: Brain Injury : [bi]. 1998 January; 12(1): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9483340
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Donepezil overdose. Author(s): Greene YM, Noviasky J, Tariot PN. Source: The Journal of Clinical Psychiatry. 1999 January; 60(1): 56-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10074883
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Donepezil overdose: a tenfold dosing error. Author(s): Shepherd G, Klein-Schwartz W, Edwards R. Source: The Annals of Pharmacotherapy. 1999 July-August; 33(7-8): 812-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466911
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Donepezil plus vitamin E as a treatment in Alzheimer disease. Author(s): Sobow T, Kloszewska I. Source: Alzheimer Disease and Associated Disorders. 2003 October-December; 17(4): 244. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657789
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Donepezil therapy in clinical practice: a randomized crossover study. Author(s): Greenberg SM, Tennis MK, Brown LB, Gomez-Isla T, Hayden DL, Schoenfeld DA, Walsh KL, Corwin C, Daffner KR, Friedman P, Meadows ME, Sperling RA, Growdon JH. Source: Archives of Neurology. 2000 January; 57(1): 94-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10634454
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Donepezil treatment of vascular dementia. Author(s): Meyer JS, Chowdhury MH, Xu G, Li YS, Quach M. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 482-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480789
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Donepezil use for advanced Alzheimer's disease--a case study from a long-term care facility. Author(s): Tariot PN, Jakimovich L. Source: Journal of the American Medical Directors Association. 2003 July-August; 4(4): 216-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837144
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Donepezil use in Alzheimer disease. Author(s): Barner EL, Gray SL. Source: The Annals of Pharmacotherapy. 1998 January; 32(1): 70-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9475825
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Donepezil use in managed Medicare: effect on health care costs and utilization. Author(s): Fillit H, Gutterman EM, Lewis B. Source: Clinical Therapeutics. 1999 December; 21(12): 2173-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10645761
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Donepezil use in the treatment of dementia associated with Down syndrome. Author(s): Cipriani G, Bianchetti A, Trabucchi M. Source: Archives of Neurology. 2003 February; 60(2): 292; Author Reply 292. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580720
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Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderatesevere Alzheimer's disease. Author(s): Onofrj M, Thomas A, Luciano AL, Iacono D, Di Rollo A, D'Andreamatteo G, Di Iorio A. Source: Clinical Neuropharmacology. 2002 July-August; 25(4): 207-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151908
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Donepezil, Alzheimer's disease and suxamethonium. Author(s): Heath ML. Source: Anaesthesia. 1997 October; 52(10): 1018. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9370854
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Donepezil, rivastigmine, and vitamin E in Alzheimer disease: a combined P300 eventrelated potentials/neuropsychologic evaluation over 6 months. Author(s): Thomas A, Iacono D, Bonanni L, D'Andreamatteo G, Onofrj M. Source: Clinical Neuropharmacology. 2001 January-February; 24(1): 31-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11290880
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Donepezil. Author(s): Bryson HM, Benfield P. Source: Drugs & Aging. 1997 March; 10(3): 234-9; Discussion 240-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9108896
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Donepezil. Pharmacoeconomic implications of therapy. Author(s): Foster RH, Plosker GL. Source: Pharmacoeconomics. 1999 July; 16(1): 99-114. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10539126
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Donepezil: a clinical review of current and emerging indications. Author(s): Roman GC, Rogers SJ. Source: Expert Opinion on Pharmacotherapy. 2004 January; 5(1): 161-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14680445
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Donepezil: a review of its use in Alzheimer's disease. Author(s): Dooley M, Lamb HM. Source: Drugs & Aging. 2000 March; 16(3): 199-226. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10803860
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Donepezil: an anticholinesterase inhibitor for Alzheimer's disease. Author(s): Shintani EY, Uchida KM. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 December 15; 54(24): 2805-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9428950
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Donepezil: tolerability and safety in Alzheimer's disease. Author(s): Pratt RD, Perdomo CA, Surick IW, Ieni JR. Source: Int J Clin Pract. 2002 November; 56(9): 710-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469988
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Donepezil-induced REM sleep augmentation enhances memory performance in elderly, healthy persons. Author(s): Schredl M, Weber B, Leins ML, Heuser I. Source: Experimental Gerontology. 2001 February; 36(2): 353-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11226748
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Donepezil-responsive alcohol-related prolonged delirium. Author(s): Hori K, Tominaga I, Inada T, Oda T, Hirai S, Hori I, Onaya M, Teramoto H. Source: Psychiatry and Clinical Neurosciences. 2003 December; 57(6): 603-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629709
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Donepezil-treated patients with probable vascular dementia demonstrate cognitive benefits. Author(s): Pratt RD, Perdomo CA. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 513-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480794
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Down syndrome and Alzheimer disease: response to donepezil. Author(s): Lott IT, Osann K, Doran E, Nelson L. Source: Archives of Neurology. 2002 July; 59(7): 1133-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117361
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Drug and Therapeutics Bulletin defends its stance over donepezil. Author(s): Collier J. Source: Bmj (Clinical Research Ed.). 1998 April 4; 316(7137): 1092. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9558999
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Drug interactions and donepezil. Author(s): Rojas-Fernandez C. Source: Journal of the American Geriatrics Society. 2000 May; 48(5): 597-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10811561
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Economic evaluation of donepezil for the treatment of Alzheimer's disease in Canada. Author(s): O'Brien BJ, Goeree R, Hux M, Iskedjian M, Blackhouse G, Gagnon M, Gauthier S. Source: Journal of the American Geriatrics Society. 1999 May; 47(5): 570-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323651
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Economic evaluation of donepezil treatment for Alzheimer's disease in Japan. Author(s): Ikeda S, Yamada Y, Ikegami N. Source: Dementia and Geriatric Cognitive Disorders. 2002; 13(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731713
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EEG changes during long-term treatment with donepezil in Alzheimer's disease patients. Author(s): Kogan EA, Korczyn AD, Virchovsky RG, Klimovizky SSh, Treves TA, Neufeld MY. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2001; 108(10): 1167-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11725819
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Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET. Author(s): Shinotoh H, Aotsuka A, Fukushi K, Nagatsuka S, Tanaka N, Ota T, Tanada S, Irie T. Source: Neurology. 2001 February 13; 56(3): 408-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11171913
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Effect of donepezil on EEG spectral analysis in Alzheimer's disease. Author(s): Balkan S, Yaras N, Mihci E, Dora B, Agar A, Yargicoglu P. Source: Acta Neurol Belg. 2003 September; 103(3): 164-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14626697
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Effectiveness of donepezil in treating Alzheimer's disease. Author(s): Garcia A. Source: Can Fam Physician. 1999 August; 45: 1858-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463081
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Effects of donepezil (Aricept) on the rapid eye movement sleep of normal subjects. Author(s): Kanbayashi T, Sugiyama T, Aizawa R, Saito Y, Ogawa Y, Kitajima T, Kaneko Y, Abe M, Shimizu T. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 307-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047608
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Effects of donepezil on cognitive functioning in Down syndrome. Author(s): Johnson N, Fahey C, Chicoine B, Chong G, Gitelman D. Source: Am J Ment Retard. 2003 November; 108(6): 367-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561111
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Effects of donepezil on emotional/behavioral symptoms in Alzheimer's disease patients. Author(s): Weiner MF, Martin-Cook K, Foster BM, Saine K, Fontaine CS, Svetlik DA. Source: The Journal of Clinical Psychiatry. 2000 July; 61(7): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10937606
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Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients. Author(s): Nobili F, Vitali P, Canfora M, Girtler N, De Leo C, Mariani G, Pupi A, Rodriguez G. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 August; 113(8): 1241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140003
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Effects of washout and dose-escalation periods on the efficacy, safety, and tolerability of galantamine in patients previously treated with donepezil: ongoing clinical trials. Author(s): Rasmusen L, Yan B, Robillard A, Dunbar F. Source: Clinical Therapeutics. 2001; 23 Suppl A: A25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11396868
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Efficacy and safety of donepezil in patients with Alzheimer's disease: results of a global, multinational, clinical experience study. Author(s): Boada-Rovira M, Brodaty H, Cras P, Baloyannis S, Emre M, Zhang R, Bahra R; 322 Study Group. Source: Drugs & Aging. 2004; 21(1): 43-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715043
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Efficacy and safety of rivastigmine in patients with Alzheimer's disease who failed to benefit from treatment with donepezil. Author(s): Auriacombe S, Pere JJ, Loria-Kanza Y, Vellas B. Source: Current Medical Research and Opinion. 2002; 18(3): 129-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094822
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Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24week, multicenter, international, randomized, placebo-controlled clinical trial. Author(s): Black S, Roman GC, Geldmacher DS, Salloway S, Hecker J, Burns A, Perdomo C, Kumar D, Pratt R; Donepezil 307 Vascular Dementia Study Group. Source: Stroke; a Journal of Cerebral Circulation. 2003 October; 34(10): 2323-30. Epub 2003 September 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970516
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Efficacy of donepezil in Alzheimer's disease: fact or artifact? Author(s): van Gool WA. Source: Neurology. 1999 January 1; 52(1): 218-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9921890
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Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. Author(s): Gauthier S, Feldman H, Hecker J, Vellas B, Ames D, Subbiah P, Whalen E, Emir B; Donepezil MSAD Study Investigators Group. Source: Int Psychogeriatr. 2002 December; 14(4): 389-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670060
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Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden. Author(s): Feldman H, Gauthier S, Hecker J, Vellas B, Emir B, Mastey V, Subbiah P; Donepezil MSAD Study Investigators Group. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 737-44. Erratum In: J Am Geriatr Soc. 2003 September; 51(9): 1331. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757558
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Equity in the new NHS: hard lessons from implementing a local healthcare policy on donepezil. Author(s): Doyle Y. Source: Bmj (Clinical Research Ed.). 2001 July 28; 323(7306): 222-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11473920
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Evidence-based psychopharmacology 1. Appraising a single therapeutic trial: what is the evidence for treating early Alzheimer's disease with donepezil? Author(s): Warner JP. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(3): 308-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10512093
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Extrapyramidal side effects in a patient treated with risperidone plus donepezil. Author(s): Magnuson TM, Keller BK, Burke WJ. Source: The American Journal of Psychiatry. 1998 October; 155(10): 1458-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9766783
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Extrapyramidal side-effect due to drug combination of risperidone and donepezil. Author(s): Liu HC, Lin SK, Sung SM. Source: Psychiatry and Clinical Neurosciences. 2002 August; 56(4): 479. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109969
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Fatal aspiration pneumonia during transition from donepezil to rivastigmine. Author(s): Taylor AM, Hoehns JD, Anderson DM, Tobert DG. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1550-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243604
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Fulminant chemical hepatitis possibly associated with donepezil and sertraline therapy. Author(s): Verrico MM, Nace DA, Towers AL. Source: Journal of the American Geriatrics Society. 2000 December; 48(12): 1659-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11129758
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Functional, cognitive and behavioral effects of donepezil in patients with moderate Alzheimer's disease. Author(s): Gauthier S, Feldman H, Hecker J, Vellas B, Emir B, Subbiah P; Donepezil MSAD Study Investigators' Group. Source: Current Medical Research and Opinion. 2002; 18(6): 347-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442882
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Getting donepezil into the nursing home. Author(s): Finucane TR. Source: Journal of the American Geriatrics Society. 2003 January; 51(1): 133-4; Author Reply 134. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534861
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Goal setting and attainment in Alzheimer's disease patients treated with donepezil. Author(s): Rockwood K, Graham JE, Fay S; ACADIE Investigators. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 November; 73(5): 500-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397141
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Guideline for primary care management of dementia. GPs may want to continue prescribing donepezil for patients. Author(s): Tapsfield WG, Jelly DM. Source: Bmj (Clinical Research Ed.). 1999 March 13; 318(7185): 732. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10215377
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How many patients complete an adequate trial of donepezil? Author(s): Roe CM, Anderson MJ, Spivack B. Source: Alzheimer Disease and Associated Disorders. 2002 January-March; 16(1): 49-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11882749
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Hypnopompic hallucinations with donepezil. Author(s): Yorston GA, Gray R. Source: Journal of Psychopharmacology (Oxford, England). 2000; 14(3): 303-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106313
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Impact of donepezil on caregiving burden for patients with Alzheimer's disease. Author(s): Fillit HM, Gutterman EM, Brooks RL. Source: Int Psychogeriatr. 2000 September; 12(3): 389-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081959
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Improvement in sundowning in dementia with Lewy bodies after treatment with donepezil. Author(s): Skjerve A, Nygaard HA. Source: International Journal of Geriatric Psychiatry. 2000 December; 15(12): 1147-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180473
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In vitro toxicity of rivastigmine and donepezil in cells of epithelial origin. Author(s): Goldblum D, Gygax M, Bohnke M, Garweg JG. Source: Ophthalmic Research. 2002 March-April; 34(2): 97-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914613
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Is donepezil effective for treating Alzheimer's disease? Author(s): Steele LS, Glazier RH. Source: Can Fam Physician. 1999 April; 45: 917-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10216789
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Is the placebo control obsolete in a world after donepezil and vitamin E? Author(s): Karlawish JH, Whitehouse PJ. Source: Archives of Neurology. 1998 November; 55(11): 1420-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9823825
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Kinematic analysis of the effects of donepezil hydrochloride on hand motor function in patients with Alzheimer dementia. Author(s): Hegerl U, Mergl R, Henkel V, Gallinat J, Kotter G, Muller-Siecheneder F, Pogarell O, Juckel G, Schroter A, Bahra R, Emir B, Laux G, Moller HJ. Source: Journal of Clinical Psychopharmacology. 2003 April; 23(2): 214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640228
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Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex. Author(s): Kuhl DE, Minoshima S, Frey KA, Foster NL, Kilbourn MR, Koeppe RA. Source: Annals of Neurology. 2000 September; 48(3): 391-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10976649
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Long term safety and efficacy of donepezil in the treatment of dementia in Alzheimer's disease in adults with Down syndrome: open label study. Author(s): Prasher VP, Adams C, Holder R; Down Syndrome Research Group. Source: International Journal of Geriatric Psychiatry. 2003 June; 18(6): 549-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789681
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Long-term effects of donepezil on P300 auditory event-related potentials in patients with Alzheimer's disease. Author(s): Katada E, Sato K, Sawaki A, Dohi Y, Ueda R, Ojika K. Source: Journal of Geriatric Psychiatry and Neurology. 2003 March; 16(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641372
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Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: an interim analysis of the results of a US multicentre open label extension study. Author(s): Rogers SL, Friedhoff LT. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1998 February; 8(1): 67-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452942
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Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: final analysis of a US multicentre open-label study. Author(s): Cochrane Database Syst Rev. 2000;(4):CD001190 Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2000 May; 10(3): 195-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034704
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Mania and donepezil. Author(s): Benazzi F, Rossi E. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1999 June; 44(5): 506-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10389619
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Mania associated with donepezil. Author(s): Benazzi F. Source: Journal of Psychiatry & Neuroscience : Jpn. 1999 November; 24(5): 468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586539
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Mania associated with donepezil. Author(s): Benazzi F. Source: International Journal of Geriatric Psychiatry. 1998 November; 13(11): 814-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9850879
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Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. Author(s): Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Source: Jama : the Journal of the American Medical Association. 2004 January 21; 291(3): 317-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734594
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Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study. Author(s): Tiseo PJ, Perdomo CA, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839761
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Neuroleptic malignant-like syndrome due to donepezil and maprotiline. Author(s): Ohkoshi N, Satoh D, Nishi M, Shoji S. Source: Neurology. 2003 March 25; 60(6): 1050-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654986
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New acetylcholinesterase inhibitor (donepezil) treatment for Alzheimer's disease in a chronic dialysis patient. Author(s): Suwata J, Kamata K, Nishijima T, Yoshikawa T, Sano M. Source: Nephron. 2002 June; 91(2): 330-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12053074
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New drug treatment for Alzheimer's disease. SMAC's advice on use of donepezil is contradictory. Author(s): Baxter T, Black D, Prempeh H. Source: Bmj (Clinical Research Ed.). 1998 October 3; 317(7163): 946. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9841011
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Open-label study of donepezil in chronic poststroke aphasia. Author(s): Berthier ML, Hinojosa J, Martin Mdel C, Fernandez I. Source: Neurology. 2003 April 8; 60(7): 1218-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682346
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Open-label study of donepezil in traumatic brain injury. Author(s): Masanic CA, Bayley MT, VanReekum R, Simard M. Source: Archives of Physical Medicine and Rehabilitation. 2001 July; 82(7): 896-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441374
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Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Author(s): Doody RS, Geldmacher DS, Gordon B, Perdomo CA, Pratt RD; Donepezil Study Group. Source: Archives of Neurology. 2001 March; 58(3): 427-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11255446
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Parkinsonism onset in a patient concurrently using tiapride and donepezil. Author(s): Cochrane Database Syst Rev. 2003;(3):CD001190 Source: Intern Med. 2000 October; 39(10): 863. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917900
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Patient populations in clinical trials of the efficacy and tolerability of donepezil in patients with vascular dementia. Author(s): Pratt RD. Source: Journal of the Neurological Sciences. 2002 November 15; 203-204: 57-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417358
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Perspectives in the management of Alzheimer's disease: clinical profile of donepezil. Author(s): Rogers SL. Source: Dementia and Geriatric Cognitive Disorders. 1998; 9 Suppl 3: 29-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853200
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Pharmacokinetic and pharmacodynamic profile of donepezil HCl following evening administration. Author(s): Tiseo PJ, Rogers SL, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839760
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Pharmacokinetic and pharmacodynamic profile of donepezil HCl following multiple oral doses. Author(s): Rogers SL, Cooper NM, Sukovaty R, Pederson JE, Lee JN, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839759
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Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses. Author(s): Rogers SL, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839758
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Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil. Author(s): Zhao Q, Xie C, Pesco-Koplowitz L, Jia X, Parier JL. Source: Journal of Clinical Pharmacology. 2003 February; 43(2): 180-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616671
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Pharmacokinetic rationale for switching from donepezil to galantamine. Author(s): Maelicke A. Source: Clinical Therapeutics. 2001; 23 Suppl A: A8-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11396871
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Pharmacotherapy for people with Alzheimer's disease: a Markov-cycle evaluation of five years' therapy using donepezil. Author(s): Stewart A, Phillips R, Dempsey G. Source: International Journal of Geriatric Psychiatry. 1998 July; 13(7): 445-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9695032
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Pisa syndrome due to a cholinesterase inhibitor (donepezil): a case report. Author(s): Miyaoka T, Seno H, Yamamori C, Inagaki T, Itoga M, Tsubouchi K, Horiguchi J. Source: The Journal of Clinical Psychiatry. 2001 July; 62(7): 573-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488374
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Possible association between donepezil and worsening Parkinson's disease. Author(s): Bourke D, Druckenbrod RW. Source: The Annals of Pharmacotherapy. 1998 May; 32(5): 610-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9606486
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Prescribing donepezil in clinical practice. Author(s): Watts-Tobin MA, Horn N. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1999 October; 175: 393. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10789315
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Presence or absence of at least one epsilon 4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease. Author(s): Rigaud AS, Traykov L, Latour F, Couderc R, Moulin F, Forette F. Source: Pharmacogenetics. 2002 July; 12(5): 415-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12142731
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Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects. Author(s): Mumenthaler MS, Yesavage JA, Taylor JL, O'Hara R, Friedman L, Lee H, Kraemer HC. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28(7): 1366-73. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784106
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Purpuric rash with donepezil treatment. Author(s): Bryant CA, Ouldred E, Jackson SH, Kinirons MT. Source: Bmj (Clinical Research Ed.). 1998 September 19; 317(7161): 787. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9740567
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Quantitative EEG and perfusional single photon emission computed tomography correlation during long-term donepezil therapy in Alzheimer's disease. Author(s): Rodriguez G, Vitali P, Canfora M, Calvini P, Girtler N, De Leo C, Piccardo A, Nobili F. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2004 January; 115(1): 39-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706467
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Quantitative EEG changes in Alzheimer patients during long-term donepezil therapy. Author(s): Rodriguez G, Vitali P, De Leo C, De Carli F, Girtler N, Nobili F. Source: Neuropsychobiology. 2002; 46(1): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207147
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Questions about donepezil. Author(s): Elie LM, Cole MG. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1998 April 21; 158(8): 1014-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9580729
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Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease. Author(s): Leroi I, Brandt J, Reich SG, Lyketsos CG, Grill S, Thompson R, Marsh L. Source: International Journal of Geriatric Psychiatry. 2004 January; 19(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716693
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Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy. Author(s): Litvan I, Phipps M, Pharr VL, Hallett M, Grafman J, Salazar A. Source: Neurology. 2001 August 14; 57(3): 467-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502915
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Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease. Author(s): Krishnan KR, Charles HC, Doraiswamy PM, Mintzer J, Weisler R, Yu X, Perdomo C, Ieni JR, Rogers S. Source: The American Journal of Psychiatry. 2003 November; 160(11): 2003-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594748
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Regional cerebral blood flow patterns and response to donepezil treatment in patients with Alzheimer's disease. Author(s): Hanyu H, Shimizu T, Tanaka Y, Takasaki M, Koizumi K, Abe K. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(4): 177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626849
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Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease. Author(s): Kaasinen V, Nagren K, Jarvenpaa T, Roivainen A, Yu M, Oikonen V, Kurki T, Rinne JO. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 615-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454562
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Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. Author(s): Sugimoto H, Ogura H, Arai Y, Limura Y, Yamanishi Y. Source: Japanese Journal of Pharmacology. 2002 May; 89(1): 7-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083745
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Responses to donepezil in Alzheimer's disease and Parkinson's disease. Author(s): Mori S. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 493-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480791
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Severe worsening of parkinsonism in Lewy body dementia due to donepezil. Author(s): Onofrj M, Thomas A. Source: Neurology. 2003 November 25; 61(10): 1452. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638981
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Simultaneous determination of donepezil (aricept) enantiomers in human plasma by liquid chromatography-electrospray tandem mass spectrometry. Author(s): Matsui K, Oda Y, Nakata H, Yoshimura T. Source: J Chromatogr B Biomed Sci Appl. 1999 June 11; 729(1-2): 147-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410937
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Study of donepezil binding to serum albumin by capillary electrophoresis and circular dichroism. Author(s): Gotti R, Bertucci C, Andrisano V, Pomponio R, Cavrini V. Source: Analytical and Bioanalytical Chemistry. 2003 November; 377(5): 875-9. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955395
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Successful use of donepezil for the treatment of dementia with Lewy bodies. Author(s): Rojas-Fernandez CH. Source: The Annals of Pharmacotherapy. 2001 February; 35(2): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11215841
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Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease. Author(s): Bergman J, Lerner V. Source: Clinical Neuropharmacology. 2002 March-April; 25(2): 107-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981238
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Sustained cognitive improvement following treatment of Alzheimer's disease with donepezil. Author(s): Evans M, Ellis A, Watson D, Chowdhury T. Source: International Journal of Geriatric Psychiatry. 2000 January; 15(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10637404
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Suxamethonium and donepezil: a cause of prolonged paralysis. Author(s): Crowe S, Collins L. Source: Anesthesiology. 2003 February; 98(2): 574-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552219
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Switching cholinesterase inhibitor therapy in Alzheimer's disease--donepezil to rivastigmine, is it worth it? Author(s): Bullock R, Connolly C. Source: International Journal of Geriatric Psychiatry. 2002 March; 17(3): 288-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11921158
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The beneficial effect of donepezil on visual hallucinations in three patients with Parkinson's disease. Author(s): Kurita A, Ochiai Y, Kono Y, Suzuki M, Inoue K. Source: Journal of Geriatric Psychiatry and Neurology. 2003 September; 16(3): 184-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967063
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The cost-effectiveness of donepezil therapy in Swedish patients with Alzheimer's disease: a Markov model. Author(s): Jonsson L, Lindgren P, Wimo A, Jonsson B, Winblad B. Source: Clinical Therapeutics. 1999 July; 21(7): 1230-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463520
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The effect of donepezil on sedation and other symptoms in patients receiving opioids for cancer pain: a pilot study. Author(s): Bruera E, Strasser F, Shen L, Palmer JL, Willey J, Driver LC, Burton AW. Source: Journal of Pain and Symptom Management. 2003 November; 26(5): 1049-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585555
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The effect of donepezil therapy on health costs in a Medicare managed care plan. Author(s): Hill JW, Futterman R, Mastey V, Fillit H. Source: Manag Care Interface. 2002 March; 15(3): 63-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11925682
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The effect of multiple doses of donepezil HCl on the pharmacokinetic and pharmacodynamic profile of warfarin. Author(s): Tiseo PJ, Foley K, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839766
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The effects of donepezil and neostigmine in a patient with unusual pseudocholinesterase activity. Author(s): Sprung J, Castellani WJ, Srinivasan V, Udayashankar S. Source: Anesthesia and Analgesia. 1998 November; 87(5): 1203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9806710
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The effects of donepezil in Alzheimer's disease - results from a multinational trial. Author(s): Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Moller HJ, Rogers SL, Friedhoff LT. Source: Dementia and Geriatric Cognitive Disorders. 1999 May-June; 10(3): 237-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10325453
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The effects of donepezil on quantitative EEG in patients with Alzheimer's disease. Author(s): Reeves RR, Struve FA, Patrick G. Source: Clin Electroencephalogr. 2002 April; 33(2): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12025738
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The effects of donepezil on the P300 auditory and visual cognitive evoked potentials of patients with Alzheimer's disease. Author(s): Reeves RR, Struve FA, Patrick G, Booker JG, Nave DW. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 1999 Fall; 7(4): 349-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10521169
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The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group. Author(s): Rogers SL, Friedhoff LT. Source: Dementia. 1996 November-December; 7(6): 293-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8915035
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The pharmacology of donepezil: a new treatment of Alzheimer's disease. Author(s): Wilkinson DG. Source: Expert Opinion on Pharmacotherapy. 1999 November; 1(1): 121-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11249555
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The relationship between donepezil and behavioral disturbances in patients with Alzheimer's disease. Author(s): Cummings JL, Donohue JA, Brooks RL. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2000 Spring; 8(2): 134-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10804074
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The value of the managed entry of new drugs: a case study of donepezil. Author(s): Payne K, Davies LM, Noyce PR, Weiss MC. Source: International Journal of Technology Assessment in Health Care. 2003 Winter; 19(1): 114-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12701944
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Therapeutic advances: donepezil for the treatment of Alzheimer's disease. Author(s): Misson J, Kendall MJ. Source: Journal of Clinical Pharmacy and Therapeutics. 1997 August; 22(4): 251-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9548205
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Therapeutic effects of an acetylcholinesterase inhibitor (donepezil) on memory in Wernicke-Korsakoff's disease. Author(s): Sahin HA, Gurvit IH, Bilgic B, Hanagasi HA, Emre M. Source: Clinical Neuropharmacology. 2002 January-February; 25(1): 16-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11852291
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Treating visual hallucinations with donepezil. Author(s): Burke WJ, Roccaforte WH, Wengel SP. Source: The American Journal of Psychiatry. 1999 July; 156(7): 1117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401470
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Treatment of REM sleep behavior disorder with donepezil: a report of three cases. Author(s): Ringman JM, Simmons JH. Source: Neurology. 2000 September 26; 55(6): 870-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10994012
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Treatment of tardive dyskinesia with donepezil. Author(s): Caroff SN, Campbell EC, Havey JC, Sullivan KA, Katz IR, Mann SC. Source: The Journal of Clinical Psychiatry. 2001 February; 62(2): 128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11247101
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Treatment of tardive dyskinesia with donepezil: a pilot study. Author(s): Caroff SN, Campbell EC, Havey J, Sullivan KA, Mann SC, Gallop R. Source: The Journal of Clinical Psychiatry. 2001 October; 62(10): 772-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816865
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Treatment with donepezil in Alzheimer patients with and without cerebrovascular disease. Author(s): Frolich L, Klinger T, Berger FM. Source: Journal of the Neurological Sciences. 2002 November 15; 203-204: 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417372
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Two cases of quetiapine augmentation for donepezil-refractory visual hallucinations in dementia with Lewy bodies. Author(s): Terao T, Shimomura T, Izumi Y, Nakamura J. Source: The Journal of Clinical Psychiatry. 2003 December; 64(12): 1520-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14728121
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Update on Alzheimer drugs (donepezil). Author(s): Smith Doody R. Source: The Neurologist. 2003 September; 9(5): 225-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12971832
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Urinary incontinence with donepezil treatment in hospitalized children and adolescents with attention deficit hyperactivity disorder. Author(s): Pachaiyappan K, Petti TA, Bangs M, Pfau B, Dumlao S. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Spring; 13(1): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804133
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Urinary incontinence: an unrecognised adverse effect with donepezil. Author(s): Hashimoto M, Imamura T, Tanimukai S, Kazui H, Mori E. Source: Lancet. 2000 August 12; 356(9229): 568. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950240
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Use of artificial networks in clinical trials: a pilot study to predict responsiveness to donepezil in Alzheimer's disease. Author(s): Mecocci P, Grossi E, Buscema M, Intraligi M, Savare R, Rinaldi P, Cherubini A, Senin U. Source: Journal of the American Geriatrics Society. 2002 November; 50(11): 1857-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12410907
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Use of donepezil for the treatment of mild-moderate Alzheimer's disease: an audit of the assessment and treatment of patients in routine clinical practice. Author(s): Cameron I, Curran S, Newton P, Petty D, Wattis J. Source: International Journal of Geriatric Psychiatry. 2000 October; 15(10): 887-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044869
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Use of donepezil for vascular dementia: preliminary clinical experience. Author(s): Mendez MF, Younesi FL, Perryman KM. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1999 Spring; 11(2): 268-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333999
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Use of donepezil in elderly patients with Alzheimer's disease--a Hawaii based study. Author(s): Alagiakrishnan K, Wong W, Blanchette PL. Source: Hawaii Med J. 2000 February; 59(2): 57-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10800254
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Violent behavior-associated with donepezil. Author(s): Bouman WP, Pinner G. Source: The American Journal of Psychiatry. 1998 November; 155(11): 1626-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9812132
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What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia. Author(s): Minett TS, Thomas A, Wilkinson LM, Daniel SL, Sanders J, Richardson J, Littlewood E, Myint P, Newby J, McKeith IG. Source: International Journal of Geriatric Psychiatry. 2003 November; 18(11): 988-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618549
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CHAPTER 2. NUTRITION AND DONEPEZIL Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and donepezil.
Finding Nutrition Studies on Donepezil 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 “donepezil” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “donepezil” (or a synonym): •
Chromaproline and Chromaperidine, nicotine agonists, and Donepezil, cholinesterase inhibitor, enhance performance of memory tasks in ovariectomized rats. Author(s): Department of Psychology, Hunter College of CUNY, 695 Park Avenue, New York, NY 10021, USA.
[email protected] Source: Luine, V N Mohan, G Tu, Z Efange, S M Pharmacol-Biochem-Behavolume 2002 December; 74(1): 213-20 0091-3057
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Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Author(s): Arizona Research Laboratories, Division of Neural Systems, Memory & Aging, University of Arizona, 384 Life Sciences North Building, Tucson,AZ 85724, USA.
[email protected] Source: Barnes, C A Meltzer, J Houston, F Orr, G McGann, K Wenk, G L Neuroscience. 2000; 99(1): 17-23 0306-4522
•
Combination of a novel antidementia drug FK960 with donepezil synergistically improves memory deficits in rats. Author(s): Department of Neuroscience, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
[email protected] Source: Tokita, K Yamazaki, S Yamazaki, M Matsuoka, N Mutoh, S Pharmacol-BiochemBehavolume 2002 October; 73(3): 511-9 0091-3057
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Donepezil reverses a mnemonic deficit produced by scopolamine but not by perforant path lesion or transient cerebral ischaemia. Author(s): PRBN, F. Hoffmann La-Roche AG., Basel, Switzerland.
[email protected] Source: Higgins, G A Enderlin, M Fimbel, R Haman, M Grottick, A J Soriano, M Richards, J G Kemp, J A Gill, R Eur-J-Neurosci. 2002 June; 15(11): 1827-40 0953-816X
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Donepezil, a centrally acting acetylcholinesterase inhibitor, alleviates learning deficits in hypocholinergic models in rats. Author(s): Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
[email protected] Source: Ogura, H Kosasa, T Kuriya, Y Yamanishi, Y Methods-Find-Exp-Clin-Pharmacol. 2000 March; 22(2): 89-95 0379-0355
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Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine. Author(s): State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, People's Republic of China Source: Zhao, Q Tang, X C Eur-J-Pharmacol. 2002 November 29; 455(2-3): 101-7 00142999
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Tacrine and donepezil attenuate the neurotoxic effect of A beta(25-35) in rat PC12 cells. Author(s): Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital B84, Sweden. Source: Svensson, A L Nordberg, A Neuroreport. 1998 May 11; 9(7): 1519-22 0959-4965
Nutrition
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND DONEPEZIL Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to donepezil. 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 donepezil 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 “donepezil” (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 donepezil: •
Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder. Author(s): Gnanadesikan M, Freeman MP, Gelenberg AJ. Source: Bipolar Disorders. 2003 June; 5(3): 203-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780874
•
Cholinesterase inhibitors and Gingko extracts--are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months' duration. Author(s): Wettstein A. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2000 January; 6(6): 393-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755847
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Diagnosis and management of Alzheimer disease. Author(s): Daly MP. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1999 September-October; 12(5): 375-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534086
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Do we have drugs for dementia? No. Author(s): Pryse-Phillips W. Source: Archives of Neurology. 1999 June; 56(6): 735-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10369315
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Featured CME topic: dementia. Medication update. Author(s): Slagle MA. Source: Southern Medical Journal. 2001 July; 94(7): 678-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11531174
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Gateways to clinical trials. Author(s): Bayes M, Rabasseda X, Prous JR. Source: Methods Find Exp Clin Pharmacol. 2002 December; 24(10): 703-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616965
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Ginkgo extract or cholinesterase inhibitors in patients with dementia: what clinical trials and guidelines fail to consider. Author(s): Schulz V. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 74-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807348
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Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Author(s): Bai DL, Tang XC, He XC. Source: Current Medicinal Chemistry. 2000 March; 7(3): 355-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10637369
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Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Author(s): Zhang HY, Tang XC. Source: Neuroscience Letters. 2000 September 29; 292(1): 41-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996445
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Huprine X is a novel high-affinity inhibitor of acetylcholinesterase that is of interest for treatment of Alzheimer's disease. Author(s): Camps P, Cusack B, Mallender WD, El Achab RE, Morral J, Munoz-Torrero D, Rosenberry TL.
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Source: Molecular Pharmacology. 2000 February; 57(2): 409-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10648652 •
Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy. Author(s): Perry EK, Pickering AT, Wang WW, Houghton PJ, Perry NS. Source: The Journal of Pharmacy and Pharmacology. 1999 May; 51(5): 527-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411211
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Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence. Author(s): Perry EK, Pickering AT, Wang WW, Houghton P, Perry NS. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 1998 Winter; 4(4): 419-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9884179
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New drugs derived from medicinal plants. Author(s): Zhang JT. Source: Therapie. 2002 March-April; 57(2): 137-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185962
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Perspectives in the treatment of vascular dementia. Author(s): Roman G. Source: Drugs Today (Barc). 2000 September; 36(9): 641-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847569
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Pharmacologic treatment of Alzheimer's disease: an update. Author(s): DeLaGarza VW. Source: American Family Physician. 2003 October 1; 68(7): 1365-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567491
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Pharmacologic treatments of dementia. Author(s): Bonner LT, Peskind ER. Source: The Medical Clinics of North America. 2002 May; 86(3): 657-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12171061
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Placebos in clinical trials in Alzheimer disease: an international discussion. Author(s): Whitehouse PJ, Arizaga R, Brodaty H, Gauthier S, Graham N, Green RC, Homma A, Mangone C, Senanarong V, Xu XH. Source: Alzheimer Disease and Associated Disorders. 1999 July-September; 13(3): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10485568
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Practice guidelines for the diagnosis and treatment of Alzheimer's disease in a managed care setting: Part II--Pharmacologic therapy. Alzheimer's Disease (AD) Managed Care Advisory Council. Author(s): Fillit H, Cummings J. Source: Manag Care Interface. 2000 January; 13(1): 51-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10747691
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Repair of amyloid beta(25-35)-induced memory impairment and synaptic loss by a Kampo formula, Zokumei-to. Author(s): Tohda C, Tamura T, Komatsu K. Source: Brain Research. 2003 November 14; 990(1-2): 141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568338
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The Effects of Ginkgo biloba Extracts on the Pharmacokinetics and Pharmacodynamics of Donepezil. Author(s): Yasui-Furukori N, Furukori H, Kaneda A, Kaneko S, Tateishi T. Source: Journal of Clinical Pharmacology. 2004 May; 44(5): 538-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15102875
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The impact of drugs against dementia on cognition in aging and mild cognitive impairment. Author(s): Ihl R. Source: Pharmacopsychiatry. 2003 June; 36 Suppl 1: S38-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13130387
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The lowdown on Ginkgo biloba. Author(s): Gold PE, Cahill L, Wenk GL. Source: Scientific American. 2003 April; 288(4): 86-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661320
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The pharmacologic treatment of Alzheimer's disease: a guide for the general psychiatrist. Author(s): Flint AJ, van Reekum R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1998 September; 43(7): 689-97. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773218
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The pharmacological effects of ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine. Author(s): Itil TM, Eralp E, Ahmed I, Kunitz A, Itil KZ. Source: Psychopharmacology Bulletin. 1998; 34(3): 391-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9803773
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Treatment of Alzheimer's disease: current status and new perspectives. Author(s): Scarpini E, Scheltens P, Feldman H. Source: Lancet. Neurology. 2003 September; 2(9): 539-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941576
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Treatment options for Alzheimer's disease. Author(s): Dinsmore ST. Source: J Am Osteopath Assoc. 1999 September; 99(9 Suppl): S6-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10730506
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What's new in Alzheimer's disease treatment? Reasons for optimism about future pharmacologic options. Author(s): Shadlen MF, Larson EB. Source: Postgraduate Medicine. 1999 January; 105(1): 109-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9924498
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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The following is a specific Web list relating to donepezil; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Alzheimer's Disease Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com
•
Herbs and Supplements Donepezil Source: Healthnotes, Inc.; www.healthnotes.com Huperzia Source: Healthnotes, Inc.; www.healthnotes.com Huperzine A Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. PATENTS ON DONEPEZIL Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “donepezil” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on donepezil, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Donepezil By performing a patent search focusing on donepezil, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on donepezil: •
Methods for treating vascular dementia Inventor(s): Pratt; Raymond (Leonia, NJ) Assignee(s): Eisai Co., Ltd. (tokyo, Jp) Patent Number: 6,458,807 Date filed: September 4, 2001 Excerpt(s): The invention describes novel methods for treating and preventing dementia caused by vascular diseases; dementia associated with Parkinson's disease; Lewy Body dementia; AIDS dementia; mild cognitive impairments; age-associated memory impairments; cognitive impairments and/or dementia associated with neurologic and/or psychiatric conditions, including epilepsy, brain tumors, brain lesions, multiple sclerosis, Down's syndrome, Rett's syndrome, progressive supranuclear palsy, frontal lobe syndrome, and schizophrenia and related psychiatric disorders; cognitive impairments caused by traumatic brain injury, post coronary artery by-pass graft surgery, electroconvulsive shock therapy, and chemotherapy, by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for treating and preventing delirium, Tourette's syndrome, myasthenia gravis, attention deficit hyperactivity disorder, autism, dyslexia, mania, depression, apathy, and myopathy associated with or caused by diabetes by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for delaying the onset of Alzheimer's disease, for enhancing cognitive functions, for treating and preventing sleep apnea, for alleviating tobacco withdrawal syndrome, and for treating the dysfunctions of Huntington's Disease by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT.RTM. Novel cholinesterase inhibitors are described in U.S. Pat. No. 4,895,841 and WO 98/39000, the disclosures of which are incorporated by reference herein in their entirety. The cholinesterase inhibitors described in U.S. Pat. No. 4,895,841 include donepezil hydrochloride or ARICEPT.RTM., which has proven to be a highly successful drug for the treatment of Alzheimer's disease. There is a need in the art for new and improved treatments for other diseases, disorders, and syndromes that are characterized by symptoms of dementia and/or cognitive impairments. The invention is directed to these, as well as other, important ends. Web site: http://www.delphion.com/details?pn=US06458807__
•
Polymorphs of donepezil hydrochloride and process for production Inventor(s): Imai; Akio (Ibaraki, JP), Ishihama; Yasushi (Ibaraki, JP), Kajima; Takashi (Ibaraki, JP), Narabu; Yukio (Ibaraki, JP), Ohtsuka; Akiyo (Ibaraki, JP), Tanaka; Tomohide (Ibaraki, JP), Watanabe; Hideaki (Ibaraki, JP) Assignee(s): Eisai Co., Ltd. (tokyo, Jp) Patent Number: 5,985,864 Date filed: June 6, 1997
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Abstract: Donepezil hydrochloride, 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2yl]methylpiperidine hydrochloride, is provided here in the form of four polymorphs which are stable against heat and humidity in the pharmaceutical use. They can be industrially produced. They are specified by peaks in X-ray powder diffraction pattern and absorption peaks in infrared absorption spectra in potassium bromide. Excerpt(s): The present invention relates to the stable polymorphs of Donepezil hydrochloride, that is, 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methyl-piperidine hydrochloride, disclosed in the example 4 of U.S. Pat. No. 4,895,841 or EP-A 296560, having an excellent efficacy as pharmaceuticals, and industrial processes for producing them. Donepezil hydrochloride shows the acetylcholine esterase-inhibitory action and is useful for the treatment of all kinds of senile dementia, in particular being useful for prevention, treatment and amelioration of Alzheimer Disease. Donepezil hydrochloride is administered orally as usual and it may be placed for distribution and storage in a period of time before the administration. It may then be stored at patient's home for about one month at the maximum because of the property of the target disease. The stability of this medicinal substance (bulk pharmaceutical chemicals) against heat and humidity during the storage period is very important. A more stable medicinal substance of Donepezil hydrochloride is, therefore, desired. It is not known, however, that polymorphs of Donepezil hydrochloride exist. No sufficiently stable medicinal substance of Donepezil hydrochloride has been found. U.S. Pat. No. 4,895,841 discloses in Example 4 that recrystalization of the crude product mixture of Donepezil hydrochloride from ethanol/isopropyl ether afforded a purified Donepezil hydrochloride. If there is a more stable crystalline form of Donepezil hydrochloride for a long period, it is more practical for distribution and storage. Web site: http://www.delphion.com/details?pn=US05985864__ •
Process and intermediates for production of donepezil and related compounds Inventor(s): Gutman; Arie L. (Haifa, IL), Nisnevich; Genady (Nesher, IL), Shkolnik; Eleonora (Nesher, IL), Tishin; Boris (Haifa, IL), Zaltzman; Igor (Haifa, IL) Assignee(s): Finetech Laboratories Ltd. (haifa, Il) Patent Number: 6,492,522 Date filed: May 24, 2001 Abstract: The present invention relates to a new process for the preparation of acetylcholinesterase inhibitors of formula (I) or a salt thereof, wherein: R.sup.1 is N-acyl4-piperidyl; N-alkoxycarbonyl-4-piperidyl; N-alkyl-4-piperidyl; N-benzyl-4-piperidyl; N-(.omega.-aralkyl)-4-piperidyl; 4-pyridyl; R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are identical or different and each represents hydrogen, straight-chain or branched alkyl, aryl, hydroxy, alkoxy, aryloxy, benzyloxy, acyloxy, alkylthio, arylthio, benzylthio, acylamino, phthalimido or halogen; n is 1, 2 or 3; m is 1, 2, 3, 4, or 5. This process comprises cyclisation of a compound of formula (II) or salts thereof, wherein R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7, m and n are as defined above; R.sup.2 is selected from a derivatised or non-derivatised carboxyl, cyano, N-substituted aminocarbonyl groups or hydrogen; R.sup.3 is selected from a derivatised or non-derivatised carboxyl, cyano or N-substituted aminocarbonyl groups, optionally in the presence of acids and/or solvents. One of the most potent acetylcholinesterase inhibitors of the class of compounds prepared according to the present invention is donepezil.
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Excerpt(s): The present application is the national stage under 35 U.S.C. 371 of international application PCT/IL99/00436, filed Aug. 11, 1999 which designated the United States, which international application was published under PCT Article 21 (2) in English. The present invention relates to a new process for the preparation of acetylcholinesterase inhibitors (anti-AchE) such as Donepezil, to some novel intermediates used in this process and to their preparation. Dementia is a chronic progressive organic mental disorder in which there is disturbance of multiple higher cortical functions including memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement. Alzheimer's Disease is the commonest cause of dementia and is characterized by degeneration of specific nerve cells, presence of neurotic plaques, and neurofibrillary tangles. Definitive diagnosis of Alzheimer's Disease requires demonstration of these characteristic pathological features in brain tissue, although in the vast majority of cases diagnosis is made on clinical grounds alone, where it is more correctly called Senile Dementia of the Alzheimer Type (SDAT). Web site: http://www.delphion.com/details?pn=US06492522__ •
Process for the preparation of 1-benzyl-4(5,6-dimethoxy-1-indanon)-2-yl) methyl piperidine hydrochloride (Donepezil HCL) Inventor(s): Pandurang; Sutar Rajiv (Maharashtra, IN), Venkatraman; Naidu Avinash (Maharashtra, IN), Vidyadhar; Joshi Shreerang (Maharashtra, IN) Assignee(s): Usv Limited, Bsd Marg. (maharashtra, In) Patent Number: 6,649,765 Date filed: February 12, 2003 Abstract: A process for the preparation of 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2yl]methylpiperidine hydrochloride (Donepezil HCl). 5,6-Dimethoxy-2-(pyridin-4yl)methylene inda-1-one is hydrogenated with a noble metal oxide catalyst in an organic solvent at 20-50.degree. C. and 10-45 psi gauge pressure. The resulting 4-[(5,6dimethoxy-1-indanon)-2-yl]methyl piperidine is alkylated with an alkylating agent in an organic solvent at 30-80.degree. C. Excerpt(s): Compound of the formula 1 commonly known as Donepezil HCl is used for treatment of Central Nerve System (CNS) disorders. U.S. Pat. No. 4,895,841 describes preparation of Donepezil HCl by reacting 5,6-dimethoxy-1-indanone with 1-benzyl-4formylpiperidine in the presence of a strong base such as lithium diisopropyl amide followed by reduction with palladium carbon catalyst (Examples 3 and 4). Overall yield of Donepezil HCl is reported to be 50.8% (62%.times.82%). U.S. Pat. No. 5,606,064 teaches the preparation of Donepezil HCl by the reaction of 5,6-dimethoxy-1-indanone with pyrindin-4-aldehyde. The resulting 5,6-dimethoxy-2-(pyridin-4-yl)methyleneinda1-one is reacted with benzyl bromide to afford 1-benzyl-4-[(5,6-dimethoxy-1-indanon-2ylidine]methyl pyridinium bromide which on reduction with platinum oxide catalyst afforded Donepezil HCl. (Examples 2, 4 and 6). Overall yield of Donepezil HCl 58.5% (87%.times.83%.times.81%). Web site: http://www.delphion.com/details?pn=US06649765__
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Use of donerezil for the treatment of functional and/or organic pain syndromes Inventor(s): Nicolodi; Maria (Fiesole, IT), Sicuteri; Federigo (Fiesole, IT) Assignee(s): Eisai., Ltd. (tokyo, Jp) Patent Number: 6,608,088 Date filed: May 7, 2001 Abstract: Methods of use of donepezil having central action for the treatment of function (migraine and primary fibromyalgia) and/or organic (amputation, "phantom limb", tumoral or traumatic denervation or autoimmune mechanism) central pain syndromes are disclosed. Excerpt(s): The present invention refers to the use of acetylcholinesterase inhibitors with high specificity and selectivity for centrally active acetylcholinesterase (resulting in an increased concentration and duration of acetylcholine in brain) for preparing pharmaceutical compositions for the treatment of functional (migraine and primary fibromyalgia) and/or organic ("phantom limb" caused by tumoral or traumatic denervation or autoimmune mechanism) central pain syndromes. Along the years migraine has been the object of deep interest and studies in view of the importance of this pathology both for the extremely large number of patients involved and because it causes (during its more serious episodes) important or total limitations to otherwise healthy subjects. Various theories were formulated in order to find an explanation to the origin of migraine. Among these theories we can remember the "dry theory" (according to which the pain is due to the pulsing distension of cephalic vessels), the "Wet theory" (which implies the sterile inflammation of the arterial vessels which became dilated and bloated), the "serotonin-theory" according to which the pathology is caused by a disorder of the serotoninergic system in the central nervous system. Web site: http://www.delphion.com/details?pn=US06608088__
Patent Applications on Donepezil As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to donepezil: •
Compositions for prevention and treatment of dementia Inventor(s): Bain, Allen I; (Vancouver, CA), Zolotoy, Alexander; (Richmond, CA) Correspondence: Kevin S Lemack; Nields & Lemack; 176 E Main Street; Westboro; MA; 01581; US Patent Application Number: 20030144255 Date filed: December 17, 2002 Abstract: 4,4'-diaminodiphenylsulphone is a bactericide and anti-inflammatory agent. It is known to have therapeutic activity against leprosy, dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposiis sarcoma, pneumocystis carinii (pneumonia), subcorneal pustular dermatosis and cystic acne, in
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This has been a common practice outside the United States prior to December 2000.
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patients in need of such therapy. It is also known to have therapeutic activity against memory loss in patients in need of such therapy, including patients suffering from Alzheimer disease and related neurodegenerative disorders. Donepezil hydrochloride (donepezil) is an acetylcholinesterase inhibitor that is currently used for the symptomatic treatment of Alzheimer disease in patients in need of such therapy. It has now been found that combinations of 4,4'-diaminodiphenylsulphone and cholinesterase inhibitors unexpectedly show synergistic effects in the prevention and/or treatment of dementia. The present invention relates to novel compositions and methods of preventing and/or treating dementia using combinations of 4,4'diaminodiphenylsulphone and a cholinesterase inhibitor (preferably donepezil). The method involves the administration to such individuals a drug composition of 4,4'diaminodiphenylsulphone and a cholinesterase inhibitor. The invention also relates to a method of preventing and/or treating dementia including senile dementia, that involves the use of this combination of drugs. Excerpt(s): The present invention is generally directed toward a pharmaceutical composition and method for the prevention and treatment of dementia which comprises a fixed combination of at least one 4,4'-diaminodiphenylsulphon- e compound with a cholinesterase inhibitor, although separate compositions of 4,4'diaminodiphenylsulphone and a cholinesterase inhibitor may be administered together or consecutively or separately to the patient. 4,4'-diaminodiphenylsulphone compounds, especially 4,4'-diaminodiphenylsulfone, are widely used in the pharmaceutical industry. The list of diseases responding to 4,4'-diaminodiphenylsulphone includes dermatitis herpertiformis, leprosy, asthma, malaria, rheumatoid arthritis, pneumonia and pneumocyctis carinii. Recently, it has been reported that 4,4'-diaminodiphenylsulphone is also effective in the prevention and treatment of Alzheimer disease and senile dementia (Lang P. G. J. Am. Acad. Dermatol. 1979, 1, 6: 479-492; McGeer P. L. et al., M. Dementia 1992, 3: 146-149; Coleman M. D. Br. J Dermatology 1993; 129: 507-513.). In addition to the 4,4'-diaminodiphenylsulphone compounds, a few cholinesterase inhibitors have also been studied for use in the treatment of the symptoms of Alzheimer disease. Two such compounds having cholinesterase inhibitory activity, donepezil and tacrine, are currently prescribed for the symptomatic treatment of patients with mild to moderate symptoms of dementia. These two drugs, however, only offer symptomatic relief of Alzheimer disease and do not stop the progression of the illness; they also have the drawback of hepatotoxicity and/or other cholinergic side effects. The present invention shows that by combining a cholinesterase inhibitor and 4,4'diaminodiphenylsulphone, an unexpected, synergistic effect is achieved towards the prevention and treatment of dementia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for treating cognitive impairments caused by traumatic brain injuries Inventor(s): Pratt, Raymond; (Leonia, NJ) Correspondence: Edward D. Grieff, ESQ.; Hale And Dorr Llp; 1455 Pennsylvania Avenue, NW; Washington; DC; 20004; US Patent Application Number: 20020035129 Date filed: September 4, 2001 Excerpt(s): This application claims priority to PCT Application No. PCT/US01/07027 filed Mar. 5, 2001, which claims priority to U.S. Provisional Application No. 60/259,226 filed Jan. 3, 2001, U.S. Provisional Application No. 60/220,783 filed Jul. 25, 2000, U.S.
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Provisional Application No. 60/197,610 filed Apr. 18, 2000, and U.S. Provisional Application No. 60/186,744 filed Mar. 3, 2000. The invention describes novel methods for treating and preventing cognitive impairments caused by traumatic brain injuries by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT.RTM. Novel cholinesterase inhibitors are described in U.S. Pat. No. 4,895,841 and WO 98/39000, the disclosures of which are incorporated by reference herein in their entirety. The cholinesterase inhibitors described in U.S. Pat. No. 4,895,841 include donepezil hydrochloride or ARICEPT.RTM., which has proven to be a highly successful drug for the treatment of Alzheimer's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for treating parkinson's disease Inventor(s): Pratt, Raymond; (Leonia, NJ) Correspondence: Edward D. Grieff, ESQ.; Hale And Dorr Llp; 1455 Pennsylvania Avenue, NW; Washington; DC; 20004; US Patent Application Number: 20020035128 Date filed: July 6, 2001 Abstract: The invention provides methods for treating Parkinson's disease by administering a therapeutically effective amount of at least one cholinesterase inhibitor compound, a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. A preferred cholinesterase inhibitor compound is donepezil, a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. Excerpt(s): The present application claims priority to PCT/US01/07027 filed Mar. 5, 2001, which claims priority to U.S. Provisional Application No. 60/259,226 filed Jan. 3, 2001, U.S. Provisional Application No. 60/220,783 filed Jul. 25, 2000, U.S. Provisional Application No. 60/197,610 filed Apr. 18, 2000, and U.S. Provisional Application No. 60/186,744 filed Mar. 3, 2000. The invention provides safe and effective methods for treating Parkinson's disease by administering a therapeutically effective amount of at least one cholinesterase inhibitor compound to a patient. A preferred cholinesterase inhibitor compound is donepezil. Parkinson's disease is a chronic nervous disease characterized by fine, slowly spreading tremors, rigidity, and a characteristic gait. Although the onset of Parkinson's disease may be abrupt, it generally occurs gradually. The initial symptom is often a fine tremor beginning in either a hand or a foot which may spread until it involves all of the members. The duration of Parkinson's disease is indefinite, and recovery rarely if ever occurs. Cognitive impairments and dementia may be seen in the later stages of Parkinson's disease, which is a common and significant source of morbidity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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PHARMACEUTICAL HYDROCHLORIDE
COMPOSITIONS
CONTAINING
DONEPEZIL
Inventor(s): Abu Gnim, Chalil; (US), Kaspi, Joseph; (Givatayim, IL), Uzan, Rina; (Beer Sheva, IL), Weisman, Alexander; (Kiryat Ekron, IL) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040002517 Date filed: August 1, 2002 Abstract: The invention provides a pharmaceutical composition for the treatment of dementia or Alzheimer's disease in which the active therapeutical agent is donepezil hydrochloride in an amorphous state. Excerpt(s): The present invention relates to stable, amorphous, donepezil hydrochloride and to pharmaceutical compositions containing it. Donepezil hydrochloride was found as an efficient drug for the treatment of dementia and Alzheimer's disease. Its cholinergic enhancement property is considered to be the reason for the alleviation of symptoms in patients. The drug, formulated as 5 and 10 mg film coated tablets is given once daily to the patients. The crystalline state of the active ingredient in a solid state pharmaceutical preparation may play a significant role in the behavior of the drug, once taken orally, and may influence its therapeutical effect. The crystalline state may modify the dissolution and thus influence absorption and the therapeutic effect of the drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for producing multiform crystal of donepezil hydrochloride Inventor(s): Imai, Akio; (Ibaraki, JP), Shimotani, Akihiko; (Ibaraki, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040034057 Date filed: March 18, 2003 Abstract: The present invention provides a simple method of producing polymorphic crystal (III), which has high safety to environment and the bodies of operators; is gentle to environment; and can produce at low costs; and has a high refining effect. It is a method of producing polymorphic crystal (III) of donepezil hydrochloride (chemical name: 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine.multidot.monohydrochloride) represented by the following structural formula (formula (I)), which comprises dissolving donepezil (chemical name: 1-benzyl-4-[(5,6-dimethoxy-1indanon)-2-yl]methylpiperidine) in ethanol; and adding hydrochloric acid or hydrogen chloride thereto, followed by stirring. Excerpt(s): The present invention relates to a method of industrially producing a highly stable polymorphic crystal (III) of donepezil hydrochloride (chemical name: 1-benzyl-4[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine.multidot.monohydrochloride) which is disclosed in JP-A 10-53576 (WO-A 97-46527) and has a superior effect as medicines. Donepezil hydrochloride has an acetylcholinesterase inhibitory action and is useful as an agent for treating, preventing or improving various senile dementia especially Alzheimer-type senile dementia, cerebrovascular disorder associated with cerebral apoplexy (cerebral hemorrhage and cerebral infarction), cerebral
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arteriosclerosis, head injury etc., attention-deficit, logopathy, hypobulia, attention deficit hyperactivity disorders, emotional disorders, memorization disorders, paranoid hallucinatory states, abnormal behavior etc. associated with sequelae of encephalitis, cerebral paralysis etc., etc. This agent is mostly administered for a long period of time in the forms of oral solid formulations such as tablets, capsules and granules, percutaneous absorption formulations such as ointments, tapes and suppositories, and injections. The storage stability of the agent in the course of distribution and in hospitals and homes is therefore important. Particularly, in the case of oral solid formulations prepared by mixing original drug put in a powder state with various additives, the selection of polymorphic crystal of the original drug having superior physical properties including stability is important. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for the preparation of donepezil Inventor(s): Alnabari, Mohammed; (Hura, IL), Arad, Oded; (Rehovot, IL), Kaspi, Joseph; (Givatayim, IL), Lerman, Ori; (Givatayim, IL), Sery, Yana; (Beer Sheva, IL) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20040048893 Date filed: June 11, 2003 Abstract: The invention provides a process for the preparation of a compound of the formula 6 comprising the hydrolysis and decarboxylation of a compound of the formula 5 according to the reaction: 1wherein R and R.sub.2 independently a C.sub.1-C.sub.4 alkyl group or an aralkyl group. Excerpt(s): The present invention relates to a novel process for the preparation 1-benzyl4-[(5,6-dimethoxyindan-1-on-2-yl)methyl]piperidine (Donepezil) and new intermediates thereof. Donepezil is used in the treatment of Alzheimer's disease. N-protected activated-4-methylpiperidine (1) wherein X represents a leaving group and R.sub.1 represents an N-protecting group reacts with 2-alkoxycarbonyl-5,6-dimethoxyindan-1one (2) wherein R represents a C.sub.1-C.sub.4 alkyl group or an aralkyl group affording 4-[(2-alkoxycarbonyl-5,6-dimethoxy-indan-1-on-2-yl)methyl]-N-protected piperidine)] (3). Compound 3 is deprotected affording 4-[(2-alkoxycarbonyl-5,6-dimethoxy-indan-1on-2-yl)methyl]piperidine having formula 4 wherein R is as defined above. This compound is reacted with a compound of the formula R.sub.2Y wherein R.sub.2 is a C.sub.1-C.sub.4 alkyl group or an aralkyl group and Y is a leaving group to afford compound of type 5 wherein R.sub.2 is and Y are as defined above. Compound 5 is subjected to hydrolysis followed by decarboxylation to afford compound of type 6 wherein R.sub.2 is as defined above. In case where R.sub.2 is a benzyl group compound 6 is Donepezil which is a useful drug for the treatment of Alzhiemer's disease. Novel compounds represented by general formulae 3, 4 and 5 were isolated and identified as intermediates in the said process and are parts of this invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with donepezil, 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 “donepezil” (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 donepezil. You can also use this procedure to view pending patent applications concerning donepezil. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. BOOKS ON DONEPEZIL Overview This chapter provides bibliographic book references relating to donepezil. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on donepezil include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “donepezil” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on donepezil: •
Compendium of Clinical Data for Aricept Source: Teaneck, NJ: Eisai, Inc. New York, NY: Pfizer Pharmaceuticals. 2000. Contact: Available from Eisai, Inc. Teaneck, NJ 07666. Pfizer Pharmaceuticals. New York, NY 10017. (888) 274-2378. Internet: http://www.aricept.com. Summary: This multimedia kit contains a descriptive booklet and a collection of slides about the drug Aricept (donepezil). The slides and booklet present the following compendium of clinical data for donepezil: 15- and 30-week pivotal clinical trials; 24week, placebo- controlled clinical trial; 30-week multinational clinical trial; 1- year, multinational, placebo-controlled clinical trial; 3-year, open label extension trial; and a 1year, national placebo-controlled clinical trial. The slides and booklet also present information about dosing, safety, and management issues.
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Chapters on Donepezil In order to find chapters that specifically relate to donepezil, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and donepezil 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 “donepezil” (or synonyms) into the “For these words:” box.
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CHAPTER 6. PERIODICALS AND NEWS ON DONEPEZIL Overview In this chapter, we suggest a number of news sources and present various periodicals that cover donepezil.
News Services and Press Releases One of the simplest ways of tracking press releases on donepezil 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 “donepezil” (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 donepezil. 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 “donepezil” (or synonyms). The following was recently listed in this archive for donepezil: •
Memantine added to donepezil improves Alzheimer's outcomes Source: Reuters Industry Breifing Date: January 20, 2004
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Donepezil may slow hippocampal atrophy with Alzheimer's disease Source: Reuters Industry Breifing Date: November 17, 2003
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Pfizer, Eisai say Aricept may work for dementia beyond Alzheimer's disease Source: Reuters Industry Breifing Date: April 04, 2003
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Shire study shows Alzheimer's drug Reminyl equal to Aricept in bettering patient function, CEO to resign Source: Reuters Industry Breifing Date: October 29, 2002
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Reminyl equal to Aricept in bettering Alzheimer patient function Source: Reuters Medical News Date: October 29, 2002
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Memantine improves cognition in Alzheimer's patients taking Aricept Source: Reuters Medical News Date: September 10, 2002
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Forest drug improves cognition in Alzheimer's patients taking Aricept Source: Reuters Industry Breifing Date: September 10, 2002
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Eisai files Aricept in US for vascular dementia Source: Reuters Industry Breifing Date: September 03, 2002
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Donepezil reduces severity of Down's syndrome-related dementia Source: Reuters Industry Breifing Date: July 29, 2002
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Donepezil treatment improves cognition in Parkinson's disease patients Source: Reuters Industry Breifing Date: June 21, 2002
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Pfizer, Eisai report favorable Aricept results in second indication Source: Reuters Industry Breifing Date: April 17, 2002
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Pfizer trial shows Aricept more effective than Reminyl, Shire points out study shortcomings Source: Reuters Industry Breifing Date: April 05, 2002
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Aricept benefits patients with vascular dementia Source: Reuters Industry Breifing Date: January 28, 2002
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Treatment of Alzheimer's disease with donepezil delays nursing home placement Source: Reuters Industry Breifing Date: April 10, 2001
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Pfizer's Aricept reduces cost of Alzheimer's disease care Source: Reuters Industry Breifing Date: February 09, 2001
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Donepezil relieves symptoms of REM sleep behavior disorder Source: Reuters Industry Breifing Date: October 02, 2000
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Donepezil confirmed to improve cognition in Alzheimer's patients Source: Reuters Medical News Date: January 20, 2000
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Pretreatment behavior predicts response to donepezil in Alzheimer's disease patients Source: Reuters Medical News Date: November 24, 1999
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Donepezil shows persistent benefits in Alzheimer's disease Source: Reuters Medical News Date: September 24, 1999
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Donepezil may improve behavioral symptoms in patients with Down's syndrome Source: Reuters Medical News Date: March 26, 1999
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Donepezil Improves Function In Mild To Moderate Alzheimer's Disease Source: Reuters Medical News Date: January 27, 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 “donepezil” (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
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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “donepezil” (or synonyms). If you know the name of a company that is relevant to donepezil, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “donepezil” (or synonyms).
Academic Periodicals covering Donepezil Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to donepezil. In addition to these sources, you can search for articles covering donepezil that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for donepezil. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with donepezil. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to donepezil: Donepezil •
Systemic - U.S. Brands: Aricept http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203748.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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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
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “donepezil” (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 832 3 29 4 1 869
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “donepezil” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on donepezil 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 donepezil. 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 donepezil. 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 “donepezil”:
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•
Donepezil
Other guides Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Dementia http://www.nlm.nih.gov/medlineplus/dementia.html Developmental Disabilities http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html Seniors' Health Issues http://www.nlm.nih.gov/medlineplus/seniorshealthissues.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 donepezil. 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: •
Know Your Medicine: Once-A-Day Aricept (Donepezil HCl) Source: Groton, CT: Pfizer Inc. Andover, MA: Easai Research Institute of Boston. April 1998. 11 p. Contact: Available from Pfizer Inc. Eastern Pt Road, Groton, CT 06340. (860) 441-4100. Internet: http://www.pfizer.com. Available from Easai Research Institute of Boston. 1 Corporate Drive, Andover, MA 01810. (978) 794-1117. PRICE: FREE. Item: EL181R97. Summary: This booklet is designed to help patients and families learn about Aricept (donepezil HCL), a drug used for the treatment of mild to moderate Alzheimer's disease (AD). It answers some of the most commonly asked questions about Aricept, including why it is prescribed, how it works, what are the expected effects, how long it should be taken, when and how it should be taken, what to do if a dose is missed, whether it can be taken with other medicines, and what are the most common side effects. It also provides information about AD and its symptoms, a support program for people who take Aricept and their caregivers, and general advice about taking medications. It includes a copy of the manufacturer's package insert with detailed product information. Also available in Spanish (AZDC08227).
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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Alzheimer's Disease Medications Fact Sheet Summary: This fact sheet summarizes the four FDA-approved medications for treating Alzheimer's disease--Reminyl, Exelon, Aricept, and Cognex. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6917 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 donepezil. 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/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to donepezil. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with donepezil.
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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 donepezil. 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 “donepezil” (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 “donepezil”. 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 “donepezil” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “donepezil” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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DONEPEZIL DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction
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between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]
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] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH]
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Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] 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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Ansa: A turn or bend in a thread or line; a bend in a wire; one of the patterns formed by the dermal ridges on the finger tips. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU]
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Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]
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Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Athetosis: A derangement marked by ceaseless occurrence of slow, sinuous, writhing movements, especially severe in the hands, and performed involuntarily; it may occur after hemiplegia, and is then known as posthemiplegic chorea. Called also mobile spasm. [EU] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bactericide: An agent that destroys bacteria. [EU] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basalis: Chiasmatic cistern. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] 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]
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Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] 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 Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres,
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cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH]
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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 Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] 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] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called
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the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] 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] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]
Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative
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pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or
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treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cycloserine: Antibiotic substance produced by Streptomyces garyphalus. It may be used in the treatment of resistant tuberculosis as part of a multi-drug regimen. It has also been used in urinary tract infections. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness,
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sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders.
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[NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH]
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Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dystonia: Disordered tonicity of muscle. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [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] Ethnobotany: The plant lore and agricultural customs of a people. In the field of medicine, the emphasis is on traditional medicine and the existence and medicinal uses of plants and their constituents, both historically and in modern times. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [NIH] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral
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cortex which involves the entire thickness of the brain wall. [EU] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gait: Manner or style of walking. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH]
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Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH]
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Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which
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may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH]
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Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]
Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isopropyl: A gene mutation inducer. [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] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival
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behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lipid: Fat. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU]
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Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Maprotiline: A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [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] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular
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animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU]
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Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [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] 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] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]
Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU]
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Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] 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] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]
Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Receptor Neurons: Neurons in the olfactory epithelium with proteins (receptors, odorant) that bind, and thus detect, odorants. Olfactory receptor neurons are bipolar. They send to the surface of the epithelium apical dendrites with non-motile cilia from which project odorant receptor molecules. Their unmyelinated axons synapse in the olfactory bulb of the brain. Unlike other neurons, they can be generated from precursor cells in adults. [NIH]
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Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [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] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
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]
Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of
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proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] 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] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piracetam: A compound suggested to be both a nootropic and a neuroprotective agent. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of
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organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral
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fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudocholinesterase: An aspect of cholinesterases. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other
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psychological or behavioral functions. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [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] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH]
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Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Odorant: Proteins, usually projecting from the cilia of olfactory receptor neurons, that specifically bind odorant molecules and trigger responses in the neurons. The large number of different odorant receptors appears to arise from several gene families or subfamilies rather than from DNA rearrangement. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]
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Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate
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affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH]
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Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] 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] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH]
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Sterile: Unable to produce children. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substantia Innominata: Tissue in the base of the forebrain inferior to the anterior perforated substance, and anterior to the globus pallidus and ansa lenticularis. It contains the basal nucleus of Meynert. [NIH] Succinylcholine: A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. [NIH]
Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH]
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Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tiapride: Benzamide derivative with dopamine antagonist actions similar to sulpiride. It has been used as an antipsychotic and in the treatment of various movement disorders. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU]
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Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Traction: The act of pulling. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH]
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Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH]
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Donepezil
X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]
151
INDEX A Acetylcholine, 4, 11, 13, 16, 17, 19, 75, 77, 111, 119, 136 Acidity, 111, 138 Acne, 77, 111 Actin, 111, 135 Activities of Daily Living, 10, 48, 111 Acyl, 75, 111 Adaptation, 11, 111, 130, 139 Adenosine, 111, 138, 147 Adjustment, 111 Adrenergic, 111, 114, 124 Adverse Effect, 9, 61, 111, 145 Aerobic, 111, 134 Afferent, 111, 140 Affinity, 68, 111, 112, 123 Agonist, 14, 112, 124, 136, 147 Airway, 112, 145 Akathisia, 112, 114 Alexia, 112, 125 Algorithms, 112, 116 Alkaline, 112, 117 Alkaloid, 112, 115, 136, 144, 147, 148 Alloys, 112, 137 Alternative medicine, 87, 112 Ambulatory Care, 112 Amino acid, 14, 112, 115, 124, 127, 137, 140, 144, 146, 148 Amnestic, 27, 112, 133 Amputation, 77, 112 Amyloid, 13, 14, 16, 70, 112, 118 Analog, 112, 123 Anatomical, 113, 119, 130, 144 Anemia, 113, 132 Animal model, 12, 17, 18, 113 Anionic, 16, 113 Anions, 113, 131, 144 Anorexia, 5, 113 Ansa, 113, 146 Antagonism, 113, 147 Anterior Cerebral Artery, 113, 118 Antibacterial, 113, 145 Antibiotic, 113, 122, 140, 145 Antibody, 112, 113, 120, 128, 129, 130, 133, 141, 145 Anticholinergic, 7, 36, 113, 138 Anticoagulant, 113, 149 Antidepressant, 8, 15, 113, 119, 133, 149
Antiemetic, 113, 114 Antifungal, 113, 131 Antigen, 112, 113, 120, 129, 130, 133 Anti-infective, 114, 129 Anti-inflammatory, 77, 114 Antipsychotic, 20, 29, 114, 135, 143, 147 Antispasmodic, 114, 144 Antitussive, 114, 123 Anxiety, 5, 112, 114, 140 Apathy, 19, 74, 114, 135 Aphasia, 53, 112, 114 Apnea, 114 Aqueous, 114, 115, 122, 129 Arterial, 77, 114, 118, 129, 140 Arteries, 114, 116, 122, 133, 135 Arterioles, 114, 116, 117 Arteriolosclerosis, 114 Arteriosclerosis, 81, 114, 118 Arteriovenous, 114, 118 Artery, 74, 113, 114, 116, 122, 125, 131, 141, 149 Aspartate, 115, 123 Aspiration, 49, 115 Athetosis, 34, 115 Atrial, 115, 149 Atrial Fibrillation, 115, 149 Atrophy, 28, 85, 115 Atropine, 115, 144 Atypical, 20, 28, 115, 143 Auditory, 5, 51, 59, 115, 126, 140 Autoantibodies, 115, 123 Autoimmune disease, 115, 134 Autonomic, 111, 114, 115, 138 Axons, 115, 123, 136 B Bacteria, 111, 113, 115, 125, 134, 145, 148, 149 Bacterial Physiology, 111, 115 Bactericidal, 115, 126 Bactericide, 77, 115 Basal Ganglia, 114, 115, 118, 119, 130, 132 Basalis, 12, 115 Base, 76, 115, 123, 131, 146, 147 Behavioral Symptoms, 5, 6, 38, 47, 48, 87, 115 Benzene, 115 Benzodiazepines, 7, 115 Beta-pleated, 112, 116
152
Donepezil
Bile, 116, 132 Bioavailability, 11, 116 Biochemical, 116, 144 Biological therapy, 116, 128 Biopsy, 116, 138 Biotechnology, 21, 87, 95, 116 Bipolar Disorder, 42, 67, 116 Bladder, 116, 119, 130, 134, 148 Blood Coagulation, 116, 117 Blood Platelets, 116, 144 Blood pressure, 116, 119, 129, 130, 134, 136 Blood vessel, 116, 117, 118, 119, 125, 131, 132, 146, 147, 149 Blood-Brain Barrier, 116, 131, 135, 138, 147 Bone Marrow, 115, 116, 127 Bone scan, 116, 143 Brain Injuries, 78, 79, 116 Brain Stem, 117, 118, 135 Branch, 107, 117, 137, 145, 147 Breakdown, 4, 117, 124, 127 Bronchi, 117, 147 Bronchial, 117, 129, 147 Bullous, 117, 123 C Calcification, 114, 117 Calcium, 18, 117, 120, 136 Capillary, 57, 117, 149 Capsules, 81, 117, 127 Carbon Dioxide, 117, 122, 138, 143, 149 Carcinogenic, 115, 117, 130 Cardiovascular, 25, 29, 117, 144 Carnitine, 17, 117 Case report, 26, 36, 54, 117, 120 Case series, 23, 25, 36, 39, 117, 120 Catecholamine, 117, 124, 138 Cell Division, 115, 118, 128, 133, 138, 140 Cell membrane, 118, 149 Cell proliferation, 114, 118 Cell Respiration, 118, 134, 143 Cell Survival, 118, 128 Cellulose, 118, 138 Central Nervous System, 77, 111, 115, 118, 119, 126, 127, 131, 134, 138, 144, 147 Cerebellar, 118, 148 Cerebellar Diseases, 118, 148 Cerebellum, 117, 118 Cerebral Cortex, 4, 14, 51, 118, 127, 135, 141 Cerebral hemispheres, 115, 116, 117, 118, 119, 147 Cerebral Hemorrhage, 80, 118 Cerebral Infarction, 80, 118
Cerebrovascular, 11, 61, 80, 118, 136 Cerebrum, 118, 147 Character, 119, 122 Chemoreceptor, 114, 119 Chemotherapy, 74, 119 Chin, 27, 119, 133 Cholesterol, 116, 119, 147 Choline, 17, 111, 119 Cholinergic, 4, 6, 7, 11, 12, 14, 16, 17, 18, 19, 30, 36, 78, 80, 114, 119, 136 Cholinesterase Inhibitors, 7, 10, 12, 18, 20, 35, 68, 74, 78, 79, 119, 124 Chorea, 114, 115, 119 Chromosome, 16, 119, 128, 148 Chronic, 30, 40, 52, 53, 64, 76, 79, 116, 119, 123, 130, 131, 132 Cimetidine, 32, 119 Citalopram, 15, 119 Clamp, 19, 119 Clinical Medicine, 120, 139 Clinical study, 27, 120, 122 Clinical trial, 3, 5, 8, 9, 10, 19, 47, 53, 61, 68, 69, 83, 95, 120, 122, 124, 134, 140, 142 Cloning, 116, 120 Coagulation, 116, 120, 128, 139, 149 Codeine, 120, 123 Cognition, 4, 5, 7, 8, 9, 10, 11, 16, 17, 20, 23, 40, 70, 86, 87, 120, 135 Collagen, 112, 120, 127 Collapse, 117, 120, 145 Colloidal, 120, 125, 126, 144 Combination Therapy, 120, 126 Complement, 120, 121, 139 Complementary and alternative medicine, 67, 72, 121 Complementary medicine, 67, 121 Computational Biology, 95, 121 Computed tomography, 55, 121, 143 Computerized tomography, 121 Concomitant, 8, 14, 121 Cone, 121, 146 Congestion, 114, 121 Conjunctiva, 121, 138 Connective Tissue, 116, 120, 121, 127, 143 Consciousness, 121, 122, 123, 124, 140 Constipation, 114, 121 Constitutional, 121, 134 Consumption, 121, 136, 143 Contraindications, ii, 121 Control group, 11, 122, 140, 141 Controlled clinical trial, 20, 48, 83, 122, 142
153
Controlled study, 11, 22, 24, 31, 36, 39, 40, 42, 122 Coordination, 118, 122, 134 Coronary, 74, 122, 133, 135 Coronary Thrombosis, 122, 133, 135 Cortex, 122, 125, 126, 140 Cortical, 19, 56, 76, 122, 135, 140, 144 Cultured cells, 14, 16, 122 Curative, 122, 147 Cyclic, 122, 147 Cycloserine, 23, 122 Cytochrome, 119, 122 Cytoplasm, 118, 122, 135 D Decarboxylation, 81, 122, 129 Degenerative, 18, 122, 128, 134 Delirium, 7, 34, 38, 40, 45, 74, 114, 122 Delivery of Health Care, 123, 128 Delusions, 41, 123, 141 Dendrites, 123, 136 Dentate Gyrus, 123, 129 Depressive Disorder, 123, 132 Dermatitis, 77, 78, 123 Dermatitis Herpetiformis, 77, 123 Dermatosis, 77, 123 Deuterium, 123, 129 Dextromethorphan, 17, 123 Diagnostic procedure, 73, 87, 123 Diarrhea, 5, 123 Diencephalon, 123, 135, 140, 147 Diffuse Axonal Injury, 117, 123 Digestion, 116, 124, 132, 146 Diploid, 124, 139, 148 Direct, iii, 4, 5, 10, 12, 17, 18, 89, 120, 124, 129, 142, 146 Disinfectant, 124, 126 Disorientation, 123, 124 Dissociation, 111, 124 Diuresis, 124, 147 Dizziness, 9, 124 Domesticated, 124, 128 Dopa, 124, 131 Dopamine, 114, 124, 131, 136, 143, 147 Dose-dependent, 36, 124 Double-blind, 9, 11, 12, 15, 22, 23, 24, 27, 28, 31, 39, 40, 124 Double-blinded, 12, 124 Drug Interactions, 90, 124 Duct, 124, 137 Dyes, 112, 125 Dyskinesia, 60, 114, 119, 125 Dyslexia, 74, 125
Dyspareunia, 125, 126 Dysphagia, 17, 125 Dystonia, 114, 125 E Effector, 111, 120, 125 Efficacy, 6, 8, 9, 10, 13, 17, 18, 19, 20, 24, 26, 27, 31, 32, 35, 41, 47, 48, 51, 53, 59, 67, 75, 125 Elasticity, 114, 125 Electrolyte, 123, 125, 139 Electrophoresis, 57, 125 Emboli, 125, 149 Embolism, 125, 141, 149 Embolization, 125, 149 Emollient, 125, 136 Encephalitis, 81, 125, 133 Encephalitis, Viral, 125 Endemic, 125, 132 Enhancer, 28, 125 Entorhinal Cortex, 125, 129 Environmental Health, 94, 96, 125 Enzymatic, 112, 117, 121, 126, 129 Enzyme, 4, 14, 16, 36, 111, 125, 126, 127, 137, 139, 149 Epidermis, 126, 141 Epithelial, 50, 126, 129 Epithelium, 126, 136 Escalation, 47, 126 Estradiol, 14, 126 Estrogen, 14, 126, 144, 147 Estrogen receptor, 14, 126 Estrogen Replacement Therapy, 14, 126 Ethanol, 75, 80, 119, 126 Ether, 75, 126 Ethnobotany, 69, 126 Evoked Potentials, 59, 126 Exhaustion, 113, 126, 132 Extender, 18, 126 Extracellular, 112, 121, 126 Extrapyramidal, 6, 20, 49, 112, 114, 124, 126 F Family Planning, 95, 126 Fat, 116, 125, 126, 132, 134, 143 Fetus, 126, 138, 140 Fissure, 123, 126, 140 Frontal Lobe, 74, 113, 118, 127, 139 G Gait, 79, 118, 127 Ganglia, 111, 127, 135, 138 Gas, 117, 127, 129, 149 Gastric, 117, 119, 127, 129, 137
154
Donepezil
Gastrin, 119, 127, 129 Gastrointestinal, 6, 9, 119, 126, 127, 132, 144, 146 Gastrointestinal tract, 119, 126, 127, 144 Gelatin, 127, 146 Gene, 16, 17, 19, 116, 127, 131, 139, 142 Gene Expression, 16, 19, 127 Gene Therapy, 17, 127 Genotype, 28, 127, 138 Ginkgo biloba, 11, 70, 127 Gland, 127, 144, 146 Globus Pallidus, 127, 146 Glucose, 20, 118, 127, 129 Glutamate, 16, 17, 123, 127 Glycine, 112, 127, 136 Governing Board, 127, 139 Graft, 74, 128 Gravis, 74, 128, 135 Growth, 17, 113, 118, 128, 132, 135, 138, 148 Growth factors, 17, 128 Guinea Pigs, 14, 128 H Haploid, 128, 139 Haptens, 112, 128 Health Care Costs, 4, 43, 128 Health Expenditures, 128 Health Status, 4, 128 Hemiparesis, 117, 128 Hemiplegia, 115, 128 Hemodynamics, 12, 128 Hemoglobinopathies, 127, 128 Hemorrhage, 128, 146 Hemostasis, 128, 144 Hepatic, 27, 123, 128 Hepatitis, 49, 128 Hepatocytes, 128, 129 Hepatotoxicity, 78, 129 Heredity, 127, 129 Heterogeneity, 112, 129 Hippocampus, 12, 123, 129, 132, 135, 146 Histamine, 114, 119, 129 Histology, 129, 135 Homeostasis, 18, 129 Homologous, 127, 129, 146 Hormonal, 14, 115, 126, 129 Hormone, 14, 126, 127, 129, 143 Hydrochloric Acid, 80, 129 Hydrogen, 68, 75, 80, 111, 115, 123, 129, 134, 138, 140 Hydrogen Peroxide, 68, 129 Hydrogenation, 115, 129
Hydrolysis, 81, 111, 129 Hydroxyproline, 112, 120, 129 Hypersensitivity, 129, 143 Hypertension, 114, 118, 129 Hypoglycaemia, 123, 129 Hypokinesia, 130, 137 Hypotension, 114, 130 Hypoxia, 123, 130 I Id, 65, 71, 101, 106, 108, 130 Immunology, 111, 130 Impairment, 11, 15, 18, 23, 29, 36, 37, 56, 70, 123, 125, 130, 133, 141 In vitro, 23, 33, 50, 64, 127, 130 In vivo, 12, 14, 19, 23, 33, 127, 130 Incontinence, 61, 130, 144 Indicative, 130, 137, 149 Induction, 114, 130 Infarction, 118, 130 Infection, 116, 123, 125, 130, 131, 143 Inflammation, 77, 111, 114, 123, 125, 128, 130, 139, 143 Informed Consent, 3, 130 Initiation, 7, 19, 130 Institutionalization, 10, 130 Insulator, 131, 134 Intermediate Filaments, 131, 135 Intermittent, 131, 132 Intestines, 127, 131, 144 Intoxication, 36, 123, 131, 149 Intracellular, 130, 131, 139, 142 Intracranial Aneurysm, 118, 131 Intrinsic, 33, 112, 131 Invasive, 131, 132 Ions, 111, 115, 124, 125, 129, 131 Ischemia, 115, 131 Isopropyl, 75, 131 K Kb, 94, 131 Ketoconazole, 33, 131 L Leprosy, 77, 78, 131 Leukemia, 127, 131 Levodopa, 7, 124, 131 Levorphanol, 123, 131 Library Services, 106, 131 Ligaments, 122, 131 Limbic, 131, 140 Limbic System, 131, 140 Lipid, 114, 119, 132, 134 Lithium, 67, 76, 114, 132 Liver, 9, 116, 117, 128, 129, 132, 143
155
Liver scan, 132, 143 Lobe, 113, 118, 132 Localized, 117, 128, 130, 132, 138 Locomotion, 132, 139 Long-Term Care, 43, 132 M Magnetic Resonance Imaging, 28, 132, 143 Malaria, 77, 78, 132 Malaria, Falciparum, 132 Malaria, Vivax, 132 Malignant, 52, 114, 132, 135, 143 Malnutrition, 115, 132 Mammary, 132, 147 Mania, 52, 74, 132 Manic, 114, 116, 132, 133, 141 Manic-depressive psychosis, 133, 141 Maprotiline, 52, 133 Medial, 19, 114, 127, 133 Mediate, 18, 124, 133 Mediator, 124, 133, 144 Medical Staff, 124, 133 Medicament, 133, 146 MEDLINE, 95, 133 Medullary, 123, 133, 141 Meiosis, 133, 146 Membranes, 117, 131, 133, 138 Memory, 5, 8, 9, 11, 12, 15, 16, 18, 19, 37, 38, 40, 42, 45, 60, 64, 70, 74, 76, 78, 113, 123, 133 Memory Disorders, 9, 133 Meninges, 118, 133 Menopause, 133, 139 Mental Disorders, 130, 133, 140, 141 Mental Retardation, 11, 133 Mesolimbic, 114, 133 Metabolite, 14, 133 MI, 109, 133 Microbe, 133, 147 Microbiology, 111, 115, 134 Microorganism, 134, 149 Microscopy, 19, 134 Microtubule-Associated Proteins, 134, 135 Microtubules, 131, 134, 135 Mitochondria, 19, 134 Modification, 112, 134, 141 Molecular, 14, 17, 18, 69, 95, 97, 116, 121, 123, 126, 134, 135, 142, 148 Molecule, 113, 115, 120, 124, 125, 128, 129, 134, 142 Monitor, 17, 134 Motility, 134, 144 Motion Sickness, 134, 135, 144
Movement Disorders, 37, 114, 134, 147 Multicenter study, 6, 41, 134 Multiple sclerosis, 13, 22, 74, 134 Muscle relaxant, 134, 135, 146, 147 Muscle Relaxation, 134, 146 Myasthenia, 74, 134, 135 Mydriatic, 134, 144 Myelin, 134, 135 Myocardial infarction, 122, 133, 135, 149 Myocardium, 133, 135 Myopathy, 74, 135 N Nausea, 5, 113, 114, 135 Need, 3, 19, 74, 78, 83, 84, 102, 111, 135 Neocortex, 135 Neoplasm, 135, 143 Neostigmine, 59, 135 Nerve, 16, 76, 111, 115, 119, 123, 133, 134, 135, 136, 139, 144, 146, 148 Nervous System, 111, 118, 133, 135, 136, 138, 146 Networks, 61, 135 Neural, 17, 31, 46, 64, 111, 112, 135 Neurobehavioral Manifestations, 117, 123, 135 Neurofibrillary Tangles, 76, 135 Neurofilaments, 135 Neuroleptic, 20, 52, 112, 114, 135 Neurologic, 74, 117, 136 Neuromuscular, 111, 136, 148 Neuromuscular Junction, 111, 136 Neuronal, 9, 12, 14, 17, 18, 56, 119, 135, 136 Neurons, 12, 16, 17, 18, 123, 127, 131, 134, 135, 136, 142, 146 Neurosis, 136 Neurotic, 76, 136 Neurotoxic, 16, 64, 136 Neurotoxicity, 123, 136 Neurotransmitter, 111, 112, 119, 124, 127, 129, 136, 146 Nicotine, 55, 64, 136 Nimodipine, 19, 136 Nuclei, 113, 127, 132, 136, 140 Nucleus, 12, 19, 113, 122, 123, 127, 131, 133, 136, 140, 146 Nutritional Status, 17, 136 O Ointments, 81, 136 Olfactory Bulb, 136 Olfactory Receptor Neurons, 17, 136, 142 Orthostatic, 114, 137
156
Donepezil
Osmotic, 137, 144 Osteoporosis, 126, 137 Outpatient, 137 Ovariectomy, 14, 137 Ovaries, 137 Ovary, 126, 137 Overdose, 42, 43, 137 P Palladium, 76, 137 Palliative, 137, 147 Palsy, 42, 56, 74, 137 Pancreatic, 117, 137 Paralysis, 58, 81, 128, 137 Parkinsonism, 7, 20, 53, 57, 114, 131, 137 Paroxetine, 15, 35, 137 Patch, 19, 137 Pathogenesis, 16, 137 Pathologic, 116, 122, 129, 137 Patient Education, 100, 104, 106, 109, 137 Pepsin, 119, 137 Pepsin A, 119, 137 Peptide, 14, 16, 112, 137, 140 Percutaneous, 81, 138 Peripheral Nervous System, 128, 136, 137, 138, 146 PH, 55, 138 Phantom, 77, 138 Pharmacokinetic, 32, 33, 36, 54, 58, 138 Pharmacologic, 12, 15, 69, 70, 71, 138, 148 Pharmacotherapy, 11, 15, 25, 43, 44, 49, 54, 55, 57, 59, 138 Phenotype, 16, 138 Phosphorus, 117, 138 Physiologic, 112, 124, 130, 138, 142, 148 Physiology, 19, 138 Physostigmine, 64, 135, 138 Pilot study, 22, 58, 60, 61, 138 Piracetam, 17, 138 Placenta, 126, 138 Plant Oils, 136, 138 Plants, 69, 112, 115, 117, 119, 126, 127, 138, 148 Plasma, 34, 57, 118, 126, 127, 128, 139, 144 Plasma protein, 139, 144 Plasticity, 64, 139 Platinum, 76, 137, 139 Pneumonia, 49, 77, 78, 122, 139 Poisoning, 123, 131, 135, 139 Polymorphic, 80, 123, 139 Postmenopausal, 14, 126, 137, 139 Postoperative, 38, 139 Postsynaptic, 36, 139, 146
Post-traumatic, 117, 134, 139 Potassium, 75, 139 Potentiate, 14, 139 Potentiation, 119, 139 Practice Guidelines, 96, 139 Preclinical, 4, 139 Precursor, 13, 14, 16, 119, 124, 125, 126, 131, 136, 139, 148 Prefrontal Cortex, 19, 139 Premedication, 140, 144 Prenatal, 17, 140 Presynaptic, 36, 136, 140, 146 Primary endpoint, 11, 140 Progression, 8, 9, 15, 16, 18, 78, 113, 140 Progressive, 8, 18, 27, 42, 56, 74, 76, 114, 123, 126, 128, 140, 143 Projection, 136, 140 Prophase, 140, 146 Prophylaxis, 140, 149 Protein S, 116, 140 Proteins, 17, 112, 113, 118, 120, 131, 134, 135, 136, 137, 138, 139, 140, 142, 144, 148 Protocol, 15, 140 Protons, 129, 140, 141 Protozoan, 132, 140 Proximal, 140, 144 Proxy, 3, 140 Pruritic, 123, 140 Pseudocholinesterase, 59, 140 Psychiatric, 74, 133, 140 Psychic, 133, 136, 140, 141, 144 Psychoactive, 55, 140, 149 Psychomotor, 123, 135, 141 Psychopharmacology, 22, 25, 30, 36, 37, 38, 39, 40, 41, 42, 48, 50, 51, 56, 61, 70, 141 Psychosis, 20, 39, 114, 141 Psychotropic, 38, 141 Public Policy, 95, 141 Pulmonary, 116, 121, 141, 149 Pulmonary Embolism, 141, 149 Pulse, 134, 141 Pustular, 77, 141 Pyramidal Tracts, 126, 141 Q Quality of Life, 5, 6, 8, 10, 11, 15, 141 Quaternary, 141, 144, 146 R Radiation, 124, 138, 141, 143, 150 Radiation therapy, 124, 141 Radioactive, 116, 129, 132, 141, 143 Radiological, 138, 141
157
Random Allocation, 141, 142 Randomization, 12, 15, 142 Randomized, 5, 8, 9, 11, 20, 22, 23, 24, 27, 37, 42, 43, 48, 52, 56, 59, 125, 142 Randomized clinical trial, 8, 142 Randomized Controlled Trials, 5, 142 Reagent, 129, 142 Reality Testing, 141, 142 Receptor, 14, 17, 111, 113, 119, 121, 123, 124, 126, 136, 142, 144 Receptors, Odorant, 136, 142 Receptors, Serotonin, 142, 144 Recombination, 127, 142 Rectum, 127, 130, 142, 146 Recurrence, 15, 116, 133, 142 Refer, 1, 120, 124, 127, 132, 135, 141, 142, 144 Refraction, 142, 145 Refractory, 7, 61, 142 Regimen, 6, 122, 125, 138, 142 Relaxant, 143, 146 Remission, 116, 133, 142, 143 Renal failure, 123, 143 Research Design, 3, 12, 143 Respiration, 114, 117, 119, 134, 143 Retrospective, 25, 143 Retroviral vector, 127, 143 Rheumatism, 143 Rheumatoid, 77, 78, 143 Rheumatoid arthritis, 77, 78, 143 Rigidity, 79, 137, 138, 143 Risperidone, 23, 31, 49, 54, 143 Rod, 119, 143 S Sarcoma, 77, 143 Scans, 13, 143 Scatter, 138, 143 Schizoid, 143, 149 Schizophrenia, 23, 28, 29, 37, 38, 41, 42, 74, 133, 143, 144, 149 Schizotypal Personality Disorder, 143, 149 Sclerosis, 114, 134, 144 Scopolamine, 64, 144 Screening, 120, 144 Secretion, 16, 119, 129, 144 Segmental, 16, 144 Segmentation, 144 Seizures, 123, 144 Selective estrogen receptor modulator, 144, 147 Self Care, 111, 144 Senile, 75, 76, 78, 80, 137, 144
Septal, 113, 132, 144 Septum, 19, 144 Septum Pellucidum, 144 Serotonin, 77, 114, 119, 136, 137, 138, 142, 143, 144, 148 Sertraline, 24, 49, 144 Serum, 7, 57, 120, 144 Serum Albumin, 57, 144 Shock, 74, 145, 148 Side effect, 6, 12, 13, 20, 49, 78, 89, 100, 111, 112, 114, 116, 119, 124, 133, 145, 147 Skeletal, 119, 145, 146 Sleep apnea, 74, 145 Small intestine, 129, 131, 145 Social Environment, 141, 145 Social Security, 142, 145 Solvent, 76, 115, 126, 137, 145 Somatic, 131, 133, 138, 140, 145 Spasm, 114, 115, 145 Spatial disorientation, 124, 145 Specialist, 8, 102, 145 Species, 124, 127, 128, 132, 133, 145, 149 Specificity, 16, 77, 112, 145 Spectrum, 13, 131, 145 Sperm, 119, 145 Spinal cord, 117, 118, 119, 128, 133, 135, 138, 141, 145 Staging, 143, 145 Steel, 119, 145 Sterile, 77, 146 Stimulant, 129, 146, 147 Stimulus, 126, 146 Stomach, 127, 129, 131, 135, 137, 145, 146 Stool, 130, 146 Stress, 20, 117, 135, 143, 146 Stroke, 18, 29, 48, 94, 146 Subiculum, 129, 146 Substance P, 122, 133, 144, 146 Substantia Innominata, 28, 146 Succinylcholine, 34, 35, 146 Suppositories, 81, 127, 146 Symptomatic, 78, 146 Symptomatic treatment, 78, 146 Synapse, 111, 136, 140, 146, 148 Synapsis, 146 Synaptic, 70, 136, 146 Synaptic Transmission, 136, 146 Synergistic, 18, 78, 147 Systemic, 90, 116, 123, 128, 130, 135, 141, 147, 149 T Tacrine, 9, 16, 23, 64, 70, 78, 147
158
Donepezil
Tamoxifen, 14, 144, 147 Tardive, 60, 114, 119, 147 Telencephalon, 115, 118, 147 Temporal, 129, 147 Testis, 126, 147 Thalamus, 123, 132, 140, 147 Theophylline, 33, 147 Therapeutics, 26, 27, 35, 43, 45, 47, 54, 58, 60, 90, 147 Thrombosis, 140, 146, 147 Tiapride, 53, 147 Tin, 139, 147 Tomography, 11, 51, 121, 143, 147 Tooth Preparation, 111, 147 Topical, 126, 129, 147 Toxic, iv, 9, 115, 136, 147, 148 Toxicity, 50, 124, 138, 147 Toxicology, 18, 96, 148 Toxins, 113, 125, 130, 148 Traction, 119, 148 Transfection, 116, 127, 148 Transfusion, 126, 148 Translation, 112, 148 Transmitter, 111, 124, 133, 148 Trauma, 29, 117, 118, 123, 148 Treatment Failure, 9, 148 Tremor, 79, 137, 148 Tricyclic, 119, 133, 148 Trigger zone, 114, 148 Trisomy, 16, 148 Tryptophan, 120, 144, 148 Tubocurarine, 135, 148
U Ubiquitin, 135, 148 Unconscious, 130, 148 Urinary, 61, 119, 122, 130, 144, 148 Urinary tract, 122, 148 Urinary tract infection, 122, 148 Urine, 116, 124, 130, 148 V Vaccine, 140, 149 Vascular, 12, 42, 43, 45, 48, 53, 62, 69, 74, 86, 130, 138, 149 Vasomotor, 126, 149 Venlafaxine, 15, 149 Venous, 114, 118, 140, 149 Venous blood, 118, 149 Venous Thrombosis, 149 Ventricle, 129, 141, 147, 149 Venules, 116, 117, 149 Vesicular, 123, 149 Veterinary Medicine, 95, 149 Virulence, 147, 149 Virus, 125, 143, 149 Vitro, 149 Vivo, 19, 149 Voltage-gated, 19, 149 W Wakefulness, 123, 149 Warfarin, 58, 149 Withdrawal, 74, 123, 149 X Xenograft, 113, 149 X-ray, 75, 121, 141, 143, 150 Y Yeasts, 138, 150
159
160
Donepezil
