We read the paper by Garsed et al,1 which revives interest in 5-hydroxytryptamine (5-HT) receptor antagonists as treatment for diarrhoea-predominant irritable bowel syndrome (IBS-D). As a highly prevalent functional gastrointestinal (GI) disorder,2 without a known organic pathology to target, IBS continues to be challenging to treat. Interest in agents acting on 5-HT receptors selectively is not novel, with alosetron, the most well-studied 5-HT₃ antagonist, demonstrating efficacy in treating IBS-D.3 However, cases of severe constipation and ischaemic colitis led to the withdrawal of the drug. Ondansetron first demonstrated effects on GI transit over …