Kishibayashi N, Karasawa A
Department of Pharmacology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd, Shizuoka, Japan.
J Pharm Pharmacol. 1998 Sep;50(9):1045-50. doi: 10.1111/j.2042-7158.1998.tb06920.x.
KW-5092 (2-[1-[2-[[5-(piperidinomethyl)-2-furanyl] methylamino]ethyl]imidazonylidin-2-ylidenene]malononitrile fumarate) is a novel gastroprokinetic agent with both acetylcholine release facilitatory and acetylcholinesterase inhibitory activity. We have investigated the effects of KW-5092 on antroduodenal coordination and gastric emptying in guinea-pigs. In the guinea-pig isolated gastroduodenal preparation, KW-5092 at 3 x 10(-7) to 3 x 10(-6) M significantly increased antroduodenal coordination. The effect of KW-5092 was almost completely inhibited by atropine or tetrodotoxin. Cisapride, a gastroprokinetic agent with acetylcholine release facilitatory activity, also increased coordination whereas neither acetylcholine nor the acetylcholinesterase inhibitor neostigmine affected it. In-vivo, KW-5092 and cisapride enhanced gastric emptying whereas neostigmine delayed it. These results suggest that acetylcholine release facilitation, but not acetylcholinesterase inhibition, is involved in the enhancement by KW-5092 of antroduodenal coordination and gastric emptying.
KW-5092（富马酸2-[1-[2-[[5-(哌啶甲基)-2-呋喃基]甲基氨基]乙基]咪唑烷-2-亚基]丙二腈）是一种新型促胃肠动力药物，具有促进乙酰胆碱释放和抑制乙酰胆碱酯酶的活性。我们研究了KW-5092对豚鼠胃十二指肠协调性和胃排空的影响。在豚鼠离体胃十二指肠制备中，3×10^(-7)至3×10^(-6)M的KW-5092显著增强胃十二指肠协调性。KW-5092的作用几乎完全被阿托品或河豚毒素抑制。西沙必利是一种具有促进乙酰胆碱释放活性的促胃肠动力药物，也能增强协调性，而乙酰胆碱和乙酰胆碱酯酶抑制剂新斯的明对此均无影响。在体内，KW-5092和西沙必利促进胃排空，而新斯的明则延迟胃排空。这些结果表明，KW-5092增强胃十二指肠协调性和胃排空是通过促进乙酰胆碱释放，而非抑制乙酰胆碱酯酶来实现的。
