ENHANCEMENT BY KW-5092, A NOVEL GASTROPROKINETIC AGENT, OF THE GASTROINTESTINAL MOTOR-ACTIVITY IN DOGS

KW-5092 furanyl]methyl]amino]ethyl]-2-imidazolidinylidene} propanedini trile fumarate) is a novel gastroprokinetic agent with acetylcholinest erase (AChE) inhibitory activity and acetylcholine (ACh) release facil itatory activity. The present study examined the effects of KW-5092 on gastrointestinal (GI) motor activity in dogs. In anesthetized dogs, K W-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 H-2-receptor antagonist with AChE inhibitory activity and A Ch release facilitatory activity, enhanced the motor activity but decr eased 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 enha nced the gastric antral, duodenal, ileal and the colonic motor activit ies. Neostigmine at 0.1 mg/kg, i.v. or 3 mg/kg, p.o. enhanced the duod enal, ileal and colonic motor activities, but induced excitement, slav ering, 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 mot or activity in a wide range from the gastric antrum to the colon and d oes not induce behavioral and cardiovascular side effects. KW-5092 may be a useful drug for the treatment of GI motility dysfunctions.