EFFECT OF TRIMEBUTINE MALEATE ON BETHANECHOL-INDUCED CONTRACTIONS OF GASTROINTESTINAL TRACT IN CONSCIOUS AND ANAESTHETIZED DOGS

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The effect of trimebutine maleate (TM-906) on bethanechol-induced contractions of the gastrointestinal tract in dogs was studied by means of chronically implanted force transducers, and it was compared with that of metoclopramide and atropine. During the period of motor quiescence in the fasted state of conscious dog, a bolus i.v. injection of 10 to 50 μg/kg bethanechol caused rhythmic contractions in the stomach and small intestine, in which an increase in basal tone was often accompanied in the distal ileum. The stomach responded to a less extent than the small intestine. Intravenous infusion of TM-906 at 3.0 mg/kg-hr for 20 to 60 min reduced the gastric contractions induced by 20 to 30 μg/kg bethanechol in five out of six conscious animals examined. The drug, however, enhanced the contractions of the duodenum and jejunum in a majority of the animals. Metoclopramide (1.8 mg/kg-hr) showed a tendency to potentiate the bethanechol-induced contractions in the stomach and small intestine, and atropine (0.06 mg/kg-hr) diminished them. In pentobarbital-Na anaesthetized dogs, effects of TM-906 on bethanechol-induced contractions resembled those in conscious dogs, inhibition in the stomach and potentiation in the small intestine.