Abstract: AIMTo investigat the effects of donepezil on delayed rectifier-like potassium currents (I_K) in rat hippocampus and neocortex. METHODSWhole cell configuration of the patch-clamp techniques were used to characterize I_K in acutely isolated rat hippocampal and neocortical pyramidal neurons. RESULTSThe slowly inactivating outward currents (I_K) were recorded in all cells under investigation. Donepezil in micromolar concentrations were shown to supress the I_K of all cells in a dose-dependent and voltage-dependent manner. The steady-state activation curves of I_K were characterized by half-activation potentials of -15.5 mV in hippocampal and -4.1 mV in neocortical pyramidal neurons and were changed to -26.2 mV and -18.6 mV, respectively, after perfusion with donepezil (10 μmol·L^-1). CONCLUSIONAt concentrations as low as 1 μmol·L^-1, donepezil was found to block the I_K in a voltage-dependent manner in hippocampus and neocortex. This effect may be synergistic with the anticholinesterase activity of donepezil to increase its therapeutic effectiveness.