Enhancement of defecation and distal colonic motor activity by KW-5092, a novel gastroprokinetic agent, in rats.
KW-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.
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
N
N
Kishibayashi
T
T
Yokoyama
A
A
Karasawa
D000109:Acetylcholine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003672:Defecation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D009570:Nitriles; C081341:KW 5092; D000109:Acetylcholine