Kishibayashi N, Karasawa A
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 1995 Jan;67(1):45-50. doi: 10.1254/jjp.67.45.
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) propulsion in rats. KW-5092 at 1 to 30 mg/kg, p.o. dose-dependently enhanced the gastric emptying, small intestinal propulsion and the proximal and distal colonic propulsion. Metoclopramide, a dopamine D2-receptor antagonist with ACh release facilitatory activity, dose-dependently enhanced the gastric emptying at 0.03 to 1 mg/kg, p.o., whereas this drug did not affect the small intestinal propulsion, or the proximal and distal colonic propulsion. Neostigmine, an AChE inhibitor, dose-dependently enhanced the small intestinal propulsion and the proximal and the distal colonic propulsion at 0.3 to 10 mg/kg, p.o., whereas it delayed the gastric emptying at 10 mg/kg, p.o. The present results demonstrate that KW-5092 enhances the GI propulsion from the stomach to the colon and that metoclopramide or neostigmine enhances only the upper or the lower GI propulsion, respectively. Thus, KW-5092 may be a gastroprokinetic drug of a novel type for the treatment of GI motility dysfunctions in a wide range from the stomach to the colon.
KW-5092（富马酸（1-[2-[[[5-(哌啶甲基)-2-呋喃基]甲基]氨基]乙基]-2-咪唑烷叉基）丙二腈）是一种新型促胃肠动力剂，具有乙酰胆碱酯酶（AChE）抑制活性和乙酰胆碱（ACh）释放促进活性。本研究考察了KW-5092对大鼠胃肠（GI）推进的影响。口服1至30mg/kg的KW-5092剂量依赖性地增强胃排空、小肠推进以及近端和远端结肠推进。甲氧氯普胺是一种具有ACh释放促进活性的多巴胺D2受体拮抗剂，口服0.03至1mg/kg时剂量依赖性地增强胃排空，而该药物不影响小肠推进或近端和远端结肠推进。新斯的明是一种AChE抑制剂，口服0.3至10mg/kg时剂量依赖性地增强小肠推进以及近端和远端结肠推进，而口服10mg/kg时则延迟胃排空。目前的结果表明，KW-5092增强从胃到结肠的胃肠推进，而甲氧氯普胺或新斯的明分别仅增强上消化道或下消化道推进。因此，KW-5092可能是一种新型促胃肠动力药物，用于治疗从胃到结肠的广泛范围内的胃肠动力障碍。
