Inhibitory Effects of KW-5092, a Novel Gastroprokinetic Agent, on the Activity of Acetylcholinesterase in Guinea Pig Ileum

The Japanese Journal of Pharmacology

Nobuyuki Kishibayashi¹  Akio Ishii¹  Akira Karasawa¹ 

[1] Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.

关键词: KW-5092;    Neostigmine;    Anticholinesterase activity;    Ileum (guinea pig);   

DOI  :  10.1254/jjp.66.397

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(19)Cited-By(10)KW-5092 ({1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2-imidazolidinylidene} propanedinitrile fumarate) is a novel gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory activity and acetylcholine release facilitatory activity. The present study used guinea pig ileal homogenates to examine the inhibitory effects of KW-5092 on the activities of AChE and butyrylcholinesterase (BuChE). KW-5092 inhibited AChE and BuChE with the IC50 values of 6.8 × 10-8 M and 2.4 × 10-5 M, respectively. The IC50 values of neostigmine for AChE and BuChE were 3.6 × 10-8 M and 1.9 × 10-7 M, respectively. HSR-803 (N-[4-[2-(dimethylamino)ethoxy]benzyl]-3, 4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, inhibited AChE and BuChE with the IC50 values of 8.6 × 10-6 M and 6.0 × 10-4 M, respectively. The AChE inhibition by KW-5092 Was reversible and noncompetitive, whereas that by HSR-803 was reversible and uncompetitive. On the other hand, the AChE inhibition by neostigmine was non-competitive when the enzyme was preincubated with this inhibitor for 2 min prior to the addition of the substrate, and it was nearly competitive when the enzyme, the inhibitor and the substrate were incubated simultaneously. The present results demonstrate that KW-5092 is a selective, reversible and noncompetitive inhibitor of AChE with different characteristics from those of neostigmine and HSR-803. The AChE inhibitory action may contribute to its gastroprokinetic effect.

【 授权许可】

Unknown