Donepezil 120014-06-4

Function of Donepezil

Donepezil is a potent, reversible, specific and noncompetitive acetylcholinesterase (AChE) inhibitor for the treatment of mild to moderate dementia.

In vitro studies:

Donepezil has a reversible and non-competitive inhibitory effect on AChE. It is 500-1000-fold more selective for AChE than for BuChE. Short- and long-term drug exposure to human SH-SY5Y neuroblastoma cells induces a concentration-dependent inhibition of cell proliferation independent of muscarinic or nicotinic receptor blockade and apoptosis. Donepezil reduces the number of cells in the S-G2/M phase of the cell cycle, increases the number in the G0/G1 phase, and reduces the expression of two cyclins in the G1/S and G2/M transitions: cyclinE and cyclinB. At the same time, it also increased the expression of the cell cycle repressor p21. In addition, donepezil increases action potential-dependent dopamine release and modulates nicotinic receptors in substantia nigra dopaminergic neurons.

In vivo studies:

Donepezil absorbs Chemicalbook slowly from the gastrointestinal tract in vivo, with a terminal half-life of 50-70 hours in young volunteers and more than 100 hours in elderly. After extensive hepatic metabolism, the parent compound is 93% bound to plasma proteins. Donepezil is metabolized in the liver by the cytochrome P450 system (CYP1A2-, CYP2D6-, CYP3A4-related enzymes). In animals, donepezil was unchanged in the brain and no metabolites were found in neural tissue. In plasma, urine and bile, most donepezil metabolites are O-glucuronides. After oral ingestion, peak plasma concentrations are reached within 3-5 hours, and its absorption is not affected by food. Donepezil has linear pharmacokinetics in the concentration range of 1-10 mg/day. 96% of circulating donepezil is protein bound.