Tegaserod, a 5-HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects

Background: Serotonin and its type-4 (5-hydroxytryptamine(4)) receptor play a major role in the physiology of the gastrointestinal tract. The effect of intravenous and/or oral tegaserod, a 5-hydroxytryptamine(4) receptor partial agonist, on gastric emptying. small bowel transit and colonic transit has not been studied in detail in humans. Aim: To assess the pharmacodynamic effects of repeated oral and intravenous administration of tegaserod on gastric emptying and small intestine and colonic transit. Methods: A randomized, placebo-controlled, double-blind, three-way, crossover study of 6 mg oral and 0.6 mg intravenous tegaserod in 12 healthy male subjects was performed. Each treatment arm of the study involved 3 days of twice-daily administration and 1 day of daily administration of the study drugs. Results: In comparison with placebo, oral and intravenous tegaserod significantly increased the gastric emptying rate (P<0.01), accelerated colonic filling (P<0.01) and shortened colonic transit at 48 h (P<0.05). Tegaserod shortened the small intestine transit time by 30% after oral and by 37% after intravenous administration. Conclusions: In healthy subjects, tegaserod markedly accelerated gastric emptying and small intestinal transit, and induced a small but significant acceleration of colonic transit. Tegaserod can act as a promotile agent throughout the gastrointestinal tract.