Donepezil (cas:120014-06-4)

Bioactive donepezil (Aricept, Donepezilo) is a potent, reversible, specific, and non-competitive acetylcholinesterase (AChE) inhibitor for the treatment of mild to moderate dementia.

In vitro studies have shown that donepezil exhibits reversible, non-competitive inhibition of AChE. Its selectivity for AChE is 500-1000 times higher than that for BuChE. Short-term and long-term exposure to human SH-SY5Y neuroblastoma cells induces 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, cyclin E and cyclin B, during the G1/S and G2/M transitions. Simultaneously, it increases the expression of the cell cycle repressor p21. In addition, donepezil can increase action potential-dependent dopamine release and regulate nicotinic receptors in dopaminergic neurons of the substantia nigra. In vivo studies show that donepezil is slowly absorbed from the gastrointestinal tract, with a terminal half-life of 50-70 hours in young volunteers and greater than 100 hours in older adults. After extensive hepatic metabolism, the plasma protein binding rate of the parent compound is 93%. Donepezil is metabolized in the liver via the cytochrome P450 system (CYP1A2-, CYP2D6-, CYP3A4-related enzymes). In animals, donepezil remains 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 exhibits linear pharmacokinetics within the concentration range of 1-10 mg/day. 96% of circulating donepezil is protein-bound. Uses donepezil hydrochloride monohydrate is a centrally acting, reversible acetylcholinesterase inhibitor.