Kinetic study on the inhibition of acetylcholinesterase by 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (E2020).
E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride) is currently being developed as a treatment for senile dementia of the Alzheimer type. Its mechanism of action is to increase central cholinergic activity by inhibiting acetylcholinesterase (AChE) in the brain. In this study, the kinetics of the inhibitory action of E2020 on AChE was examined in comparison with its derivatives (2A1050 and 2A1034) and the reference compound tetrahydroaminoacridine (THA) all of which have a similar action. Analysis of the data using Lineweaver-Burk plots shows that inhibition by the test compounds fell into the category of mixed type. Inhibitor dissociation constants for the free enzyme (KI) and acetyl-enzyme (KI) of E2020 are one or two orders of magnitude lower than those of 2A1050, 2A1034 and THA. These findings indicate the strong inhibitory effect of E2020 on AChE.
Nochi
S
S
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Asakawa
N
N
Sato
T
T
D000110:Acetylcholinesterase / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D002384:Catalysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D007700:Kinetics; D010880:Piperidines / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D000110:Acetylcholinesterase