Donepezil: An anticholinesterase inhibitor for Alzheimer’s disease
Abstract
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of donepezil are reviewed. Donepezil is a synthetic noncovalent reversible inhibitor of acetylcholinesterase (AChE) for the treatment of mild to moderate dementia associated with Alzheimer's disease. In contrast to tacrine hydrochloride, the only comparable agent currently approved by FDA, donepezil exhibits a relatively high degree of selectivity for neuronal AChE as opposed to butyrylcholinesterase. It has a half-life of 60 hours in young adults and 104 hours in elderly patients. In clinical trials, donepezil has been associated with significant improvements in Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Interview-Based Impression of Change scores. The most common adverse effects associated with donepezil are nausea, diarrhea, anorexia, and vomiting, which are most likely to occur during dose initiation or adjustment. Hepatotoxicity, a dose-limiting adverse effect that sometimes requires discontinuation of tacrine, has not been reported with donepezil. Donepezil does not appear to interact with theophylline, cimetidine, warfarin, or digoxin. Ketoconazole and quinidine inhibit the metabolism of donepezil in vitro, but there is a lack of clinical data showing that these drugs decrease the clearance of donepezil. The initial recommended dosage is 5 mg daily before bedtime, with a dosage increase to 10 mg after four to six weeks according to the patient's response and tolerance. Donepezil appears to be preferable to tacrine as the initial agent for patients with mild to moderate dementia associated with Alzheimer's disease.
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CYP450 is involved in the metabolism of drugs used for the management of Alzheimer's disease.
“CYP450 is involved in the metabolism of drugs used for management of AD [270,271].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [271]
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- Authors
- Shintani, E. Y., & Uchida, K. M.
- Affiliations
- MemorialCare Long Beach Medical Center (US)
- University of California, Irvine Medical Center (US)
- Corresponding author
- Shintani, Ellen Y.
- Venue
- American Journal of Health-System Pharmacy
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-12-15
- Volume
- 54
- Issue
- 24
- Pages
- 2805-2810
- ISSN
- 1079-2082 (ISSN-L)
- 1535-2900
- OpenAlex
- W1820407896
- Cited by
- 108
- References
- 0
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Health-System Pharmacy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- donepezil, acetylcholinesterase inhibitors, Alzheimer's disease, dementia, tacrine, pharmacokinetics, adverse drug reactions, drug interactions, dosage and administration, hepatotoxicity, cognitive function
- MeSH terms
- Donepezil, Aged, Alzheimer Disease, Anorexia, Cholinesterase Inhibitors, Diarrhea, Drug Administration Schedule, Drug Interactions, Humans, Indans, Nausea, Piperidines
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