Disease relevance of 2-[1-[2-[[5-(1-piperidylmethyl)-2-furyl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile

• KW-5092 may be a useful drug in the treatment of constipation [1].

Psychiatry related information on 2-[1-[2-[[5-(1-piperidylmethyl)-2-furyl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile

• The present study examined the effects of KW-5092 on gastrointestinal (GI) motor activity in dogs [2].

High impact information on 2-[1-[2-[[5-(1-piperidylmethyl)-2-furyl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile

• These results suggest that KW-5092 stimulates intraluminal 5-HT release from luminally perfused proximal colon of the guinea-pig via the stimulation of cholinergic neurons [3].
• Oral administration of KW-5092, a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release enhancing activities, causes a dose-dependent increase in the blood acetylcholine content of beagle dogs [4].
• Oral administration of KW-5092 (10-30 mg/kg), a gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory and ACh release enhancing activities, caused a dose-dependent increase in the ACh content of both the blood and plasma, as well as several behavioral side effects due to peripheral cholinergic stimulation [4].
• These results demonstrate that the blood ACh of beagle dogs is present mainly in the blood cells and to a lesser degree in the plasma, and that KW-5092 increased the blood ACh content mainly by increasing the plasma ACh concentration [4].
• Thus, the acceleration of intestinal motility by KW-5092 was found in vivo to be associated with an increase in ACh release from the intestinal cholinergic neurons [5].

Biological context of 2-[1-[2-[[5-(1-piperidylmethyl)-2-furyl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile

• Stimulating effects of KW-5092, a novel gastroprokinetic agent, on the gastric emptying, small intestinal propulsion and colonic propulsion in rats [6].
• The present results suggest that KW-5092 enhances the peristalsis via the inhibition of acetylcholinesterase, resulting in the intestinal propulsion [7].
• KW-5092 inhibited AChE and BuChE with the IC50 values of 6.8 x 10(-8) M and 2.4 x 10(-5) M, respectively [8].
• The present study examined the effects of KW-5092 on the defecation and colonic motor activity in rats [1].

Anatomical context of 2-[1-[2-[[5-(1-piperidylmethyl)-2-furyl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile

• Inhibitory effects of KW-5092, a novel gastroprokinetic agent, on the activity of acetylcholinesterase in guinea pig ileum [8].
• 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 [2].
• These results demonstrate that KW-5092 or neostigmine at the gastroprokinetic doses does not affect intestinal water or electrolyte transport in rats, suggesting that cholinergic activation enhances gastrointestinal motility rather than intestinal secretion of water and electrolytes [9].

Associations of 2-[1-[2-[[5-(1-piperidylmethyl)-2-furyl]methylamino]ethyl]imidazolidin-2-ylidene]propanedinitrile with other chemical compounds

• In-vivo, KW-5092 and cisapride enhanced gastric emptying whereas neostigmine delayed it [10].
• Recently, we reported that a ranitidine derivative 2 (fumarate: KW-5092), which had a 2-imidazolidinylidene propanedinitrile moiety (A), showed potent gastrointestinal motility enhancing activity [11].

References