Donepezil induces ventricular arrhythmias by delayed repolarisation

Naunyn Schmiedebergs Arch Pharmacol. 2021 Mar;394(3):559-560. doi: 10.1007/s00210-020-02028-4. Epub 2020 Nov 24.

Abstract

Acetylcholinesterase inhibitors such as donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, it is becoming apparent that cholinesterase inhibition by donepezil is not confined to the brain. This is supported by previous case reports of peripheral cholinergic side effects and adverse cardiac arrhythmias such as Torsades de Pointes which are reversible upon cessation of donepezil. The augmented acetylcholine concentrations and IKr inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect.

Keywords: Cardiac arrhythmias; Cholinesterase inhibitors; Donepezil; Electrocardiography.

Publication types

  • Comment

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Animals
  • Arrhythmias, Cardiac / chemically induced
  • Atrioventricular Block*
  • Cholinesterase Inhibitors
  • Dogs
  • Donepezil
  • Halothane
  • Indans
  • Piperidines

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Donepezil
  • Halothane