Effects of trimebutine and metoclopramide on colonic motility in guinea-pig.

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The effects of trimebutine (2-dimethylamino-2-phenylbutyl-3, 4, 5-trimethoxy benzoate hydrogen maleate) and metoclopramide (N-diethylaminoethyl-2-methoxy-4-amino-5-chlorobenzamide) on propulsive activity of the isolated segmental colon, and on longitudinal and circular muscle layers of colon in guinea-pig were investigated. Trimebutine in doses up to 10-7g/ml slightly stimulated propulsive activity, but in doses as high as 10-7g/ml inhibited it. However, metoclopramide (10-7-10-5g/ml) stimulated propulsive activity in a dose dependent manner. Neostigmine-stimulated propulsive activity was inhibited by trimebutine (10-6g/m/) but potentiated by metoclopramide (10-5g/ml). Trimebutine (10-8-10-5g/ml) contracted circular muscle layer in a dose depen-dent manner, and contracted longitudinal muscle layre in doses up to 10-7g/ml, but in doses as high as 10-7g/ml relaxed it. While, metoclopramide (10-8-10-5g/ml) contracted both muscle layers. These results indicate that, at high doses, trimebutine-induced inhibition of propulsive activity may depend on a relaxation of longitudinal muscle, and at low doses, trimebutine-induced stimulation of propulsive activity may depend on a contraction of longitudinal muscle which was partly inhibited by atropine (10-6g/ml), though metoclopramide at low doses had little effect on propulsive activity.
日本平滑筋学会の論文