Donepezil: potential neuroprotective and disease-modifying effects

Background: There is substantial evidence from preclinical studies that cholinesterase inhibitors affect basic processes that have been implicated in Alzheimer's disease (AD) pathogenesis, suggesting that these drugs should have both disease-modifying and neuroprotective effects in humans. The evidence seems to be strongest in relation to donepezil, which is the focus of this review. Objective: To summarize the preclinical literature regarding the effects of donepezil on cellular and molecular processes underlying AD. Second, to suggest reasons for the apparent disparity between robust preclinical effects and modest clinical effects of this drug and others in its class. Methods: Articles retrieved from PubMed searches were critically reviewed and selected for relevance to the current topic. Results/conclusion: Donepezil has numerous cellular and molecular effects that should influence AD progression.