HTR3A and irritable bowel syndrome: Since 5-HT3 antagonists delay GI transit, the main adverse effect of this drug class is constipation.8 While earlier studies included IBS patients with non-constipated bowel habits (NC-IBS), later trials focused on diarrhea-predominant IBS (IBS-D).9 Ondansetron is a potent, highly selective 5HT3RA, which blocks 5HT3 receptors in the GI tract and in the central nervous system.