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.


CONCLUSIONS
Donepezil has numerous cellular and molecular effects that should influence AD progression.
Jacobson
Sandra A
SA
Research Cleo Roberts Center for Clinical Research, Sun Health Research Institute, 10515 W Santa Fe Drive, Sun City, AZ 85351, USA. Sandra.Jacobson@sunhealth.org
Sabbagh
Marwan N
MN
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077265:Donepezil; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D000077265:Donepezil