REDUCTION OF RECTAL SENSITIVITY AND POSTPRANDIAL MOTILITY BY GRANISETRON, A 5-HT(3)-RECEPTOR ANTAGONIST, IN PATIENTS WITH IRRITABLE-BOWEL-SYNDROME

The effect of granisetron, a specific 5-hydroxytryptamine 3-receptor a ntagonist, on the anorectal responses to rectal distension and a 1000- calorie meal was assessed in 12 patients with irritable bowel syndrome . Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline . Granisetron caused a dose-dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensa tions of gas, desire to defecate, urgency and discomfort were perceive d. This reached significance for all sensations at the higher dose lev el (P < 0.01). No significant changes in anal pressures, rectal compli ance or distension-induced motor activity occurred following drug admi nistration. A dose-dependent reduction in post-prandial motility was o bserved following intravenous granisetron and this was highly signific ant at 160 mcg/kg (P = 0.005). These results suggest that the 5 hydrox ytryptamine receptor antagonists may have a therapeutic role in patien ts with irritable bowel syndrome.