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Br J Pharmacol. 2017 Dec;174(23):4224-4232. doi: 10.1111/bph.14030. Epub 2017 Oct 29.

Beyond symptomatic effects: potential of donepezil as a neuroprotective agent and disease modifier in Alzheimer's disease.

Author information

1
Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.
2
Seongdong-Gu Regional Center for Dementia, Seoul, Korea.
3
Department of Neurology, National Neuroscience Institute and Duke-NUS Singapore, Singapore.
4
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
5
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
6
Division of Neurology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
7
Eisai Singapore Pte. Ltd., Singapore.

Abstract

Alzheimer's disease (AD) is associated with neurodegenerative changes resulting clinically in progressive cognitive and functional deficits. The only therapies are the cholinesterase inhibitors donepezil, galantamine and rivastigmine and the N-methyl-D-aspartate-receptor antagonist memantine. Donepezil acts primarily on the cholinergic system as a symptomatic treatment, but it also has potential for disease modification and may reduce the rate of progression of AD. This review explores the potential for disease modifying effects of donepezil. Several neuroprotective mechanisms that are independent of cholinesterase inhibition, are suggested. Donepezil has demonstrated a range of effects, including protecting against amyloid β, ischaemia and glutamate toxicity; slowing of progression of hippocampal atrophy; and up-regulation of nicotinic acetylcholine receptors. Clinically, early and continuous treatment with donepezil is considered to preserve cognitive function more effectively than delayed treatment. The possible neuroprotective effects of donepezil and the potential for disease pathway modification highlight the importance of early diagnosis and treatment initiation in AD.

PMID:
28901528
PMCID:
PMC5715569
DOI:
10.1111/bph.14030
[Indexed for MEDLINE]
Free PMC Article

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