Review article: the therapeutic potential of 5-HT3 receptor antagonists inthe treatment of irritable bowel syndrome

There is evidence from studies, in both animals and humans, that 5-HT3 rece ptor blockade has potential value in the treatment of irritable bowel syndr ome, particularly in those patients with diarrhoea-predominant bowel habits . New findings suggest that 5-HT3 receptors exist on gut afferent neurones and that their activation by locally released 5-HT leads to visceral nocice ptive stimulation, in addition to increased neuronally-mediated motor and s ecretory activity. If this concept is validated, it will provide a rational e for the use of 5-HT3 receptor antagonists in patients with increased gut motility, reduced fluid absorption and low nociceptive thresholds leading t o abdominal pain. Alosetron is a highly selective, potent 5-HT3 receptor antagonist which is well absorbed with a long pharmacodynamic half-life. Its ability to provide longlasting blockade of 5-HT3 receptors throughout the body make it an ide al candidate within its class to evaluate the clinical hypothesis that sust ained and ubiquitous 5-HT3 receptor blockade is of value in the treatment o f IBS.