Effect of a novel 5‐HT3 receptor agonist MKC‐733 on upper gastrointestinal motility in humans

Summary Background : Although 5‐HT3 antagonists have been used to treat chemotherapy‐induced emesis and diarrhoea‐predominant irritable bowel syndrome, the effects of 5‐HT3 agonists in humans are unknown. Aim : To determine the effect of MKC‐733, a selective 5‐HT3 receptor agonist, on upper gastrointestinal motility. Methods : Oral MKC‐733 (0.2, 1 and 4 mg) was compared with placebo in three randomized, double‐blind, cross‐over studies in healthy males. Antroduodenal manometry was recorded for 8 h during fasting and 3 h post‐prandially (n = 12). Gastric emptying and small intestinal transit were determined by gamma‐scintigraphy (n = 16). Gastric emptying, accommodation and antral motility were determined by echoplanar magnetic resonance imaging (n = 12). Results : MKC‐733 (4 mg) increased the number of migrating motor complexes recorded in the antrum and duodenum (P