title: Stimulating effects of KW-5092, a novel gastroprokinetic agent, on the gastric emptying, small intestinal propulsion and colonic propulsion in rats.
abstract: 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 (ACh) release facilitatory activity. The present study examined the effects of KW-5092 on gastrointestinal (GI) propulsion in rats. KW-5092 at 1 to 30 mg/kg, p.o. dose-dependently enhanced the gastric emptying, small intestinal propulsion and the proximal and distal colonic propulsion. Metoclopramide, a dopamine D2-receptor antagonist with ACh release facilitatory activity, dose-dependently enhanced the gastric emptying at 0.03 to 1 mg/kg, p.o., whereas this drug did not affect the small intestinal propulsion, or the proximal and distal colonic propulsion. Neostigmine, an AChE inhibitor, dose-dependently enhanced the small intestinal propulsion and the proximal and the distal colonic propulsion at 0.3 to 10 mg/kg, p.o., whereas it delayed the gastric emptying at 10 mg/kg, p.o. The present results demonstrate that KW-5092 enhances the GI propulsion from the stomach to the colon and that metoclopramide or neostigmine enhances only the upper or the lower GI propulsion, respectively. Thus, KW-5092 may be a gastroprokinetic drug of a novel type for the treatment of GI motility dysfunctions in a wide range from the stomach to the colon.
authors.affiliation: Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kishibayashi
authors.forename: A
authors.initials: A
authors.lastname: Karasawa
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D009388:Neostigmine / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007093:Imidazoles; D009570:Nitriles; C081341:KW 5092; D009388:Neostigmine; D008787:Metoclopramide