Enhancement by KW-5092, a Novel Gastroprokinetic Agent, of the Gastrointestinal Motor Activity in Dogs

• Published in: Japanese journal of pharmacology 1994, Vol.65(2), pp.131-142
• Main Authors: Kishibayashi, Nobuyuki, Tomaru, Atsushi, Ichikawa, Shunji, Kitazawa, Takio, Shuto, Katsuichi, Ishii, Akio, Karasawa, Akira
• Format: Article
• Language: English
• Subjects: Choline esterase inhibitor; Gastrointestinal motility; KW-5092; Neostigmine; Ranitidine
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.65.131

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) motor activity in dogs. In anesthetized dogs, KW-5092 at 0.03 to 1 mg/kg, i.v. dose-dependently enhanced the gastric antral and the colonic motor activity. Neostigmine, an AChE inhibitor, enhanced the motor activity at 0.03 and 0.1 mg/kg, i.v. Ranitidine, a histamine H2-receptor antagonist with AChE inhibitory activity and ACh release facilitatory activity, enhanced the motor activity but decreased blood pressure at 1 to 10 mg/kg, i.v. In conscious dogs, KW-5092 at 0.03 to 1 mg/kg, i.v. or 1 to 10 mg/kg, p.o. dose-dependently enhanced the gastric antral, duodenal, ileal and the colonic motor activities. Neostigmine at 0.1 mg/kg, i.v. or 3 mg/kg, p.o. enhanced the duodenal, ileal and colonic motor activities, but induced excitement, slavering, vomiting and diarrhea. Ranitidine at 3 mg/kg, i.v. enhanced the gastric antral and colonic motor activities, but induced collapse or akinesia. The present results suggest that KW-5092 enhances the GI motor activity in a wide range from the gastric antrum to the colon and does not induce behavioral and cardiovascular side effects. KW-5092 may be a useful drug for the treatment of GI motility dysfunctions.