Donepezil (Aricept)

Mechanism of action

Reversibly inhibits acetylcholinesterase in the central nervous system, preventing acetylcholine breakdown and prolonging cholinergic synaptic signaling. The selectivity for CNS over peripheral AChE reduces (but doesn't eliminate) peripheral cholinergic side effects (nausea, bradycardia). Long elimination half-life (70 hours) supports once-daily dosing.

History

Donepezil (E2020) was developed by Eisai Pharmaceuticals and approved by the FDA in 1996 as the second cholinesterase inhibitor for Alzheimer's disease (after tacrine, which was withdrawn for hepatotoxicity). The improved tolerability and once-daily dosing made donepezil the dominant agent in the class. Generic availability since 2010 has reduced cost substantially. The Birks 2018 Cochrane review consolidates the efficacy evidence.

Benefits

• Cognitive function in mild-to-moderate Alzheimer's

  EVIDENCEA

  Birks 2018 Cochrane review.

• Functional decline slowing

  EVIDENCEA

  Multiple long-term RCTs.

Side effects

• Nausea, vomitingcommonmoderate
• Insomnia, vivid dreamscommonmoderate
• Bradycardiauncommonmoderate

Cited research

• Donepezil for Alzheimer's disease: Cochrane review (Birks)2018
  PMID 29923184 ↗
• Donepezil long-term effects: AD2000 trial (Courtney)2004
  PMID 15183673 ↗
• Donepezil mechanism review (Bryson)1997
  PMID 9024486 ↗

Ad Affiliate links — we may earn a commission at no extra cost to you.

No approved reviews yet. Be the first.