Effects of SK-951, a benzofuran derivative, as a prokinetic agent in rats and dogs

The gastrokinetic activity of SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0]o ctan-5-yl)ethyl]-5-chloro-2,3-dihydro-2-methylbenzo[b]furan-7-carboxamide h emifumarate), a benzofuran derivative with 5-hydroxytryptamine (5-HT)(4)-re ceptor agonist activity, was studied in rats and dogs. The effects of SK-95 1 were also investigated in a model of vagotomy-induced gastroparesis in co mparison with cisapride. In rats, both SK-951 and cisapride enhanced gastri c emptying of liquids (phenol red) at a dose of 1-100 mg/kg, p.o. Gastric e mptying of liquid (acetaminophen) in fasted beagle dogs was enhanced signif icantly by SK-951 (1.0 mg/kg, i.v.), whereas the effect of cisapride (0.2-1 .0 mg/kg, i.v.) was not statically significant. Similar results were found when radiopaque markers were given with standard meal to dogs with vagotomy -induced gastroparesis. The delayed gastric emptying of radiopaque markers by vagotomy was reversed by SK-951 (1.0 mg/kg, i.v.), whereas cisapride sho wed no effect at doses from 0.1 to 1.0 mg/kg, i.v. These results indicated that oral and intravenous administration of SK-951 accelerates gastric empt ying of both liquids and solids in animal models. Thus, SK-951 may be a hig hly potent and useful prokinetic agent in comparison to cisapride.