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 acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of donepezil and some other cholinesterase (ChE) inhibitors which have been developed for the treatment of Alzheimer's disease. The carbamate derivatives physostigmine and rivastigmine needed preincubation to exhibit appropriate anti-ChE activity. The maximum ChE inhibition by physostigmine developed within 30-60 min, while the inhibitory effect of rivastigmine on AChE and BuChE activities reached its peak after 48 and 6 h, respectively. The order of inhibitory potency (IC50) towards AChE activity under optimal assay conditions for each ChE inhibitor was: physostigmine (0.67 nM) > rivastigmine (4.3 nM) > donepezil (6.7 nM) > TAK-147 (12 nM) > tacrine (77 nM) > ipidacrine (270 nM). The benzylpiperidine derivatives donepezil and TAK-147 showed high selectivity for AChE over BuChE. The carbamate derivatives showed moderate selectivity, while the 4-aminopyridine derivatives tacrine and ipidacrine showed no selectivity. The inhibitory potency of these ChE inhibitors towards AChE activity may illustrate their potential in vivo activity.
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
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H
Ogura
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T
Kosasa
Y
Y
Kuriya
Y
Y
Yamanishi
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D048448:Phenylcarbamates; D010830:Physostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D000068836:Rivastigmine; D013619:Tacrine / Q000494:pharmacology; D013997:Time Factors
D000634:Aminoquinolines; D001552:Benzazepines; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D013619:Tacrine; C099872:TAK 147; D000077265:Donepezil; D010830:Physostigmine; C049860:amiridine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000068836:Rivastigmine