Donepezil

2022-11-16:

Donepezil #

• Developed under the ‘cholinergic hypothesis’ of Alzheimer’s, i.e. over-activation of ACE, which isn’t always the truth let alone the whole story.
• Acetylcholinesterase inhibitor and σ1 agonist (14.6 nM).
  • Non-competitive inhibitor, unlike galantamine
• Inhibits voltage-activated Sodium Channel currents and delays Kir currents and fast transient potassium currents.
• [Mechanisms of alpha7-nicotinic receptor up-regulation and sensitization to donepezil induced by chronic donepezil treatment.]
  • Upregulates α7 nAChR in the hippocampus. This was prevented by coadministration with PI3K inhibitor.
• Donepezil impairs memory in healthy older subjects: behavioural, EEG and simultaneous EEG/fMRI biomarkers
• Donepezil modulates nicotinic receptors of substantia nigra dopaminergic neurones
• Modulates α4β2, I think.
  • Depressed Nicotine currents that were in vitro “induced by brief puffer pulses, through a glass micropipette positioned above the slice”.