Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice

The role of 5-HT3 receptors in the control of intestinal propulsive activity was investigated in mice by a simple method in which the time taken for excretion of the head of an orally administered non-absorbable marker (whole gut transit time) was measured. Selective 5-HT3 receptor antagonists ramosetron (YM060) at 0.01-0.3 mg/kg s. c. and ondansetron at 0.1-1 mg/kg s.c. dose-dependently prolonged the whole gut transit time. Prokinetic benzamides, such as renzapride (0.3-10 mg/kg s.c.), zacopride (0.01-0.3 mg/kg s.c.) and cisapride (0.1-3 mg/kg s.c.), which have been reported to possess 5-HT3 receptor blocking properties, also dose-dependently prolonged it. These results indicate that activation of 5-HT3 receptors seems to be one factor that underlies the physiological control of intestinal propulsive activity in mice. In contrast to their beneficial therapeutic effects on gastroduodenal dysmotility, prokinetic benzamides, at least those which have 5-HT3 receptor antagonistic activity, may be unsuitable in the treatment of impaired lower intestinal propulsive activity.