Donepezil induces ventricular arrhythmias by delayed repolarisation

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 I-Kr inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect.

Automated summary

Acetylcholinesterase inhibitors like donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, these inhibitors may also have effects outside of the brain, leading to peripheral cholinergic side effects and adverse cardiac arrhythmias like Torsades de Pointes which are reversible upon discontinuation of the medication. Increased acetylcholine concentrations and I-Kr inhibition in cardiomyocytes caused by donepezil are thought to be responsible for these effects.