Gastroprokinetic Effect of a New Benzamide Derivative Itopride and Its Action Mechanisms in Conscious Dogs

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    • IWANAGA Yuji
    • Research and Development Division, Hokuriku Seiyaku, Co., Ltd.
    • MORIKAWA Koji
    • Research and Development Division, Hokuriku Seiyaku, Co., Ltd.
    • ITOH Zen
    • GI Laboratories, Institute for Molecular and Cellular Regulation, Gunma University


The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered intraduodenally (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 metoclopramide also stimulated gastric motility, and their threshold doses were 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 immediately restored by itopride at a dose of 3 mg/kg, i.d. With itopride at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contractions 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 itopride stimulates gastric motility through both anti-dopaminergic and anti-acetylcholinesterase actions. Its gastroprokinetic threshold dose was as large as 3-10 times those of cisapride, domperidone and metoclopramide. These findings suggest that itopride is an orally active gastroprokinetic with a moderate anti-emetic action.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 71(2), 129-137, 1996-06

    The Japanese Pharmacological Society

References:  18

Cited by:  1


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