GASTROPROKINETIC EFFECT OF A NEW BENZAMIDE DERIVATIVE ITOPRIDE AND ITS ACTION MECHANISMS IN CONSCIOUS DOGS

The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered i ntraduodenally (i.d.). Gastrointestinal motility was measured by means of chronically implanted force transducers, and itopride at a dose of 10 mg/kg, i.d. or more increased the gastric contractile force during the digestive state. Intraduodenal cisapride, domperidone and metoclo pramide also stimulated gastric motility, and their threshold doses we re 1, 3 and 1 mg/kg, respectively. Dopamine infusion (1 mg/kg/hr, i.v. ) caused the postprandial gastric motility to disappear, but it was im mediately restored by itopride at a dose of 3 mg/kg, i.d. With itoprid e at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contr actions were greatly enhanced. In addition to its gastric stimulation, itopride at doses of 10-100 mg/kg, p.o. inhibited apomorphine (0.1 mg /kg, s.c.)-induced vomiting in dogs. In conclusion, intraduodenal itop ride stimulates gastric motility through both anti-dopaminergic and an ti-acetylcholinesterase actions. Its gastroprokinetic threshold dose w as as large as 3-10 times those of cisapride, domperidone and metoclop ramide. These findings suggest that itopride is an orally active gastr oprokinetic with a moderate anti-emetic action.