Abstracto

Cilansetron: a novel, high-affinity 5-HT3 receptor antagonist for irritable bowel syndrome with diarrhea predominance

Georges Coremans

Irritable bowel syndrome (IBS) is associated with significant morbidity, impaired quality of life, work absenteeism and high healthcare costs. Current drug treatments, with the exception of drugs targeting serotonin receptor subtypes, are of limited value. Tegaserod (Zelnorm™, Novartis Pharmaceuticals Corp., NJ, USA), a partial agonist, is useful in women with the constipation-predominant form of IBS. Alosetron (Lotronex™, GlaxoSmithKline plc, London, UK), a 5-HT3 receptor antagonist, is effective in women with severe diarrheapredominant IBS; however, its use is limited and it is restricted to the USA. Cilansetron is a potent and selective 5-HT3 receptor antagonist that is being developed for IBS with diarrhea predominance (IBS-D). It delays colonic transit and reduces visceral hypersensitivity. In large, randomized controlled trials, cilansetron has been shown to improve global and specific IBS-D symptoms, including abdominal pain/discomfort, stool frequency, stool consistency, urgency and health-related quality of life in men and women. Cilansetron is well-tolerated, with constipation being the most frequent adverse event. Treatment with cilansetron, similar to that with alosetron, is associated with a low incidence of suspected ischemic colitis events. Alosetron was withdrawn temporarily from the US market, and indefinitely from the European market because of severe complications of ischemic colitis. To date, the few suspected ischemic colitis events associated with cilansetron have resolved within 30 days of drug discontinuation, without any complications. Epidemiologic studies indicate that patients with IBS have a greater risk of ischemic colitis, irrespective of treatment; this underscores the need for additional research on the natural history of IBS and potential treatment-related adverse events.