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

Abstract

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) 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 in hibitor, enhanced the motor activity at 0.03 and 0.1 mg/kg, i.v. Ranitidine, a histamine H2-receptor an tagonist 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 activ ities. Neostigmine at 0.1 mg/kg, i.v. or 3 mg/kg, p.o. enhanced the duodenal, ileal and colonic motor activ ities, 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.

Stimulatory Action of Itopride Hydrochloride on Colonic Motor Activity in Vitro and in Vivo

“…Basically, neostigmine dose dependently and significantly enhanced the antral and colinc motor activity in dogs at 30 and 100 g/kg i.v. but tended to increase blood pressure and to suppress respiration (Kishibayashi et al, 1994). Also, dogs often collapsed when neostigmine was intravenously administered at 1000 g/kg (Iwanaga et al, 1990).…”

Inhibitory Effects of KW-5092, a Novel Gastroprokinetic Agent, on the Activity of Acetylcholinesterase in Guinea Pig Ileum

“…AChE is the main enzyme responsible for the inacti vation of ACh, whereas the physiological function of BuChE remains unknown (3). KW-5092 ({ 1 [2 [ [[5 (piperidinomethyl) 2 furanyl] methyl] amino] ethyl] -2-imidazolidinylidene} propanedi nitrile fumarate) is a newly synthesized gastroprokinetic agent that dose-dependently enhances GI motility in an esthetized rabbits (4) and both conscious and anesthe tized dogs (5). In conscious dogs, KW-5092 enhances the GI motility from the gastric antrum to the colon (5).…”

“…KW-5092 ({ 1 [2 [ [[5 (piperidinomethyl) 2 furanyl] methyl] amino] ethyl] -2-imidazolidinylidene} propanedi nitrile fumarate) is a newly synthesized gastroprokinetic agent that dose-dependently enhances GI motility in an esthetized rabbits (4) and both conscious and anesthe tized dogs (5). In conscious dogs, KW-5092 enhances the GI motility from the gastric antrum to the colon (5). In the in vitro study, KW-5092 was a potent inhibitor of AChE de rived from rat brain, its inhibitory activity being equipo tent to that of neostigmine (4).…”

KW-5092, a Novel Gastroprokinetic Agent, Reverses the Norepinephrine-Induced Decline of the Gastric Mucosal Blood Flow in Rats

“…fumarate) is a newly synthesized gastroprokinetic agent, which enhances gastrointestinal motilities in a wide range from the stomach to the colon (4,5). In the guinea pig ileum, KW-5092 enhances acetylcholine (ACh) release from enteric neurons (6) and inhibits acetylcholinesterase (AChE) (7).…”