Omeprazole-induced slowing of gastrointestinal transit in mice can be countered with tegaserod

Omeprazole, besides suppressing gastric acid, causes delayed gastric emptying, which may be associated with aggravated dyspeptic symptoms. Effects of omeprazole on small intestinal transit are unknown. In this study, we evaluated in mice if (a) omeprazole affects transit of a meal through the stomach and small intestine and (b) co-treatment with the promotility agent, tegaserod, can prevent the slowing effect of omeprazole. Omeprazole (40-150 mg/kg, i.p. once daily for 5 days) delayed gastric emptying of the meal in a dose-related manner. Small intestinal transit was then evaluated at the lowest dose of omeprazole (40 mg/kg) that did not retard gastric emptying. Such transit was significantly delayed after this dose of omeprazole compared with vehicle-treated controls. When tegaserod (0.10 mg/kg) was administered concomitantly with the omeprazole, small intestinal transit of the meal was not slowed and was not different from controls. These results show that omeprazole reduces aboral transit of luminal contents through the stomach and small bowel of mice and that this delay is reversed by tegaserod.