Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice
1996
Abstract The role of 5-HT 3 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-HT 3 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-HT 3 receptor blocking properties, also dose-dependently prolonged it. These results indicate that activation of 5-HT 3 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-HT 3 receptor antagonistic activity, may be unsuitable in the treatment of impaired lower intestinal propulsive activity.
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