A Comparative Study on the Effects of Domperidone, Metoclopramide, Clebopride and Trimebutine on the Gastro-Duodenal Preparation of the Guinea Pig

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Abstract
Domperidone (dopamine antagonist), metoclopramide and clebopride (both dopamine antagonists and stimulators of the intramural cholinergic system), and trimebutine (spasmolytic) are used in the treatment of digestive disorders such as dyspepsia or gastritis. Our aim was to compare the effects of these compounds on the isolated intact gastroduodenal preparation of the guinea pig. Domperidone (IC50 = 10-6 M), clebopride (10-5 M) and metoclopramide (2 .times. 10-5 M) antagonized gastric relaxations induced by dopamine. In contrast with clebopride, domperidone and metoclopramide enhanced the amplitude of gastric contractions, moderately reduced contractile frequency, and enhanced antroduodenal coordination in a dose-dependent manner (EC50 for domperidone 3 .times. 10-7 M, for metoclopramide 2 .times. 10-5 M). Trimebutine reduced gastric spontaneous activity and antroduodenal coordination. Trimebutine had a direct relaxatory effect on gastric tone (EC50 = 4 .times. 10-6 M). The mechanism of this inhibitory effect remains unknown but our data indicate that it is not mediated via dopamine or opiate receptor subtypes. Conclusion: domperidone, clebopride, metoclopramide and trimebutine exert distinct and diverse effects on the motility parameters of the gastroduodenal preparation of the guinea pig. These diverging actions may help explain the differences in patients responsiveness to the treatment of digestive disorders such as dyspepsia or gastritis.