Comparison of inhibitory activities of donepezil and other cholinesterase inhibitors on acetylcholinesterase and butyrylcholinesterase in vitro

This study was designed to compare the in vitro inhibitory effects on acety lcholinesterase (AChE) and butyrylcholinesterase (BuChE) of donepezil and s ome other cholinesterase (ChE) inhibitors which have been developed for the treatment of Alzheimers disease. The carbamate derivatives physostigmine a nd rivastigmine needed preincubation to exhibit appropriate anti-ChE activi ty. The maximum ChE inhibition by physostigmine developed within 30-60 min, while the inhibitory effect of rivastigmine on AChE and BuChE activities r eached its peak after 48 and 6 h, respectively. The order of inhibitory pot ency (lC(50)) towards AChE activity under optimal assay conditions for each ChE inhibitor was: physostigmine (0.67 nM) > rivastigmine (4.3 nM) > donep ezil (6.7 nM) > TAK-147 (12 nM) > tacrine (77 nM) > ipidacrine (270 nm). Th e benzylpiperidine derivatives donepezil and TAK-147 showed high selectivit y for AChE over BuChE. The carbamate derivatives showed moderate selectivit y, while the 4-aminopyridine derivatives tacrine and ipidacrine showed no s electivity. The inhibitory potency of these ChE inhibitors towards AChE act ivity may illustrate their potential in vivo activitiy. (C) 2000 Prous Scie nce. All rights reserved.