Effects of Mosapride Citrate on the Motility of Stomach, Ileum and Colon in Conscious Guinea Pigs

Background/Aims: Mosapride citrate (Mosapride) is a relatively new selective 5-HT4 receptor agonist. Several studies have reported that mosapride selectively stimulates the upper GI motility, but not lower GI motility. However, 5-HT4 receptors are distributed in the stomach, small bowel and colon as well. In other studies, mosapride had a stimulatory effect on the lower GI tract. Therefore, we studied the effects of mosapride on the upper (stomach) and lower GI tract (ileum, proximal colon and distal colon) in conscious guinea pigs. Methods: We implanted force transducers into guinea pig`s stomach, ileum, proximal colon and distal colon. Mosapride (0, 1, 3, 10 and 30 mg/kg) was administered intragastrically through a polyethylene tube. The GI motor activity was measured by the motor index. After mosapride 10 mg/kg was administered intragastrically, atropine sulfate or GR113808 was administered intravenously. Results: Mosapride significantly stimulated the motor activities of the stomach, ileum and colon. The relative prokinetic potency of mosapride was not different among the 4 sites of the GI tract. The enhancing effect of mosapride was antagonized by atropine or GR113808, a selective 5-HT4 receptor antagonist. Conclusions: This study indicates that mosapride enhances both the upper and lower GI motility with similar potency by stimulation of the 5-HT4 receptor that is mediated by cholinergic neurons in a conscious guinea pig. Based on the possibility of obtaining similar results in humans, we suggest that mosapride may be useful for the treatment of upper and lower GI motor disorders.ope