Donepezil modulates nicotinic receptors of substantia nigra dopaminergic neurones

Silvia Di Angelantonio, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

1 The effects of donepezil, one of the most common cholinesterase inhibitors used for treatment of Alzheimer's disease, were studied on nicotinic receptors (nAChRs)-mediated postsynaptic currents, in dopaminergic neurons of the substantia nigra pars compacta, using the patch-clamp recording technique in slice preparations. 2 Donepezil (10-100 μM) selectively and reversibly depressed nicotine currents, induced by brief puffer pulses, through a glass micropipette positioned above the slice. 3 The peak amplitude fading of the responses generated by repeated test applications of low doses of nicotine was accelerated by donepezil, while it slowed the recovery of nicotine currents after a large, desensitising, dose of the same agonist. 4 Donepezil depressed even maximal responses to nicotine, revealing a noncompetitive mechanism of action; moreover, the inhibition of nAChRs was voltage and time independent. 5 Pretreatment with vesamicol or methamidophos did not prevent the reduction of nicotine-induced currents. The data indicated direct effect on nAChR, independent from the activity of donepezil as cholinesterase inhibitor.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalBritish Journal of Pharmacology
Volume141
Issue number4
DOIs
Publication statusPublished - Feb 2004

Keywords

  • Acetylcholinesterase
  • Allosteric modulator
  • Alzheimer's disease
  • Desensitisation
  • Donepezil
  • Dopaminergic neuron
  • Neuronal nicotinic receptors
  • Parkinson's disease
  • Patch clamp
  • Vesamicol

ASJC Scopus subject areas

  • Pharmacology

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