• Arch Int Pharmacodyn Ther · Mar 1995

    Comparative Study

    Enhancement of defecation and distal colonic motor activity by KW-5092, a novel gastroprokinetic agent, in rats.

    • N Kishibayashi, T Yokoyama, and A Karasawa.
    • Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
    • Arch Int Pharmacodyn Ther. 1995 Mar 1; 329 (2): 295-306.

    AbstractKW-5092 ([1-[2-[[[5-(piperidinomethyl)-2-furanyl]- methyl]amino]ethyl]-2-imidazolidinylidene]propanedinitrile fumarate) is a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release facilitatory activity. The present study examined the effects of KW-5092 on the defecation and colonic motor activity in rats. KW-5092, at 1 to 30 mg/kg, p.o., dose-dependently increased the fecal pellet output. In the in vitro study, KW-5092, at 10(-6) M to 10(-5) M, evoked contraction of the isolated distal colonic preparation. In the in vivo study, KW-5092, at 1 to 10 mg/kg, p.o., induced an increase in the distal colonic motor index, which was dose-dependently inhibited by atropine (0.1 to 1 mg/kg, i.v.). The present results suggest that KW-5092 induces the defecation in rats by enhancing the distal colonic motor activity via its acetylcholinesterase inhibitory activity and/or acetylcholine release facilitatory activity. KW-5092 may be a useful drug in the treatment of constipation.

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