Effects of 5-HT3 antagonism on postprandial gastric volume and symptoms in humans

Background: Alosetron reduces symptoms of dyspepsia, but the physiological basis for the symptomatic benefit is unclear. Aim: To assess 5-HT3 antagonism on postprandial gastric volume and symptoms after ingestion of maximum tolerable volume of a liquid meal. Methods: In 36 healthy volunteers, we assessed effects of placebo, 0.5 and 1 mg b.d. alosetron on fasting and postprandial gastric volumes (using single photon emission computed tomography) and symptoms based on 100 mm VAS, 30 min after maximum volume ingested. Results: The 5-HT3 antagonist reduced postprandial symptoms (aggregate score: P < 0.05), nausea (P < 0.001), and tended to reduce bloating (P = 0.08). Both 0.5 and 1 mg alosetron reduced nausea (P < 0.025); 1 mg alosetron reduced aggregate symptoms (P < 0.05) and bloating (P < 0.05). Effects on pain (P = 0.19) and fullness (P = 0.14) were not statistically significant. There were no significant effects of the 5-HT3 antagonist on volume of meal tolerated or on SPECT-measured fasting or postprandial gastric volumes. Conclusion: 5-HT3 antagonism reduces aggregate symptoms, nausea and bloating after a liquid meal without increase in gastric volumes, suggesting a role for 5-HT3 in afferent functions in healthy humans during the postprandial period.