COMPOUNDS POSSESSING 5-HT3 RECEPTOR ANTAGONISTIC ACTIVITY INHIBIT INTESTINAL PROPULSION IN MICE

The role of 5-HT3 receptors in the control of intestinal propulsive ac tivity was investigated in mice by a simple method in which the time t aken for excretion of the head of an orally administered non-absorbabl e marker (whole gut transit time) was measured, Selective 5-HT3 recept or antagonists ramosetron (YM060) at 0.01-0.3 mg/kg s.c. and ondansetr on at 0.1-1 mg/kg s.c. dose-dependently prolonged the whole gut transi t 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.), whi ch have been reported to possess 5-HT3 receptor blocking properties, a lso dose-dependently prolonged it. These results indicate that activat ion of 5-HT3 receptors seems to be one factor that underlies the physi ological control of intestinal propulsive activity in mice. In contras t to their beneficial therapeutic effects on gastroduodenal dysmotilit y, prokinetic benzamides, at least those which have 5-HT3 receptor ant agonistic activity, may be unsuitable in the treatment of impaired low er intestinal propulsive activity.