Alosetron and irritable bowel syndrome.
Alosetron (Lotronex, GlaxoSmithKline) is a potent and selective 5-HT(3)-receptor antagonist approved by the FDA for the treatment of women with diarrhoea-predominant irritable bowel syndrome (IBS) in whom conventional therapy has failed. Studies involving healthy volunteers and IBS patients have demonstrated a beneficial effect of treatment with alosetron on global IBS symptoms, abdominal pain and discomfort, altered bowel function as well as improvement of quality of life (QOL). Data from animals studies suggest the involvement of 5-HT(3) receptors on intrinsic primary afferent neurons in the mediation of the effect of alosetron on gastrointestinal motility and secretion. While definitive proof of a visceroanalgesic action is not available, an additional central mechanism of action is suggested by findings obtained in animal models, as well as from human brain imaging studies. Alosetron shows a greater effectiveness in women, and the role of genetic factors underlying inter-individual differences in the response to alosetron is currently under investigation. The most frequent adverse event associated with the use of alosetron is constipation and in some rare cases, the development of colonic mucosal ischaemia. In the following review, the most recent reported effects of alosetron on gastrointestinal motility, visceral sensitivity and anxiety, both in terms of preclinical and clinical data will be discussed. The impact of alosetron on QOL in IBS patients and the safety of treatment with alosetron, will also be covered.
Mayer
Emeran A
EA
Center for Neurovisceral Sciences & Women's Health, VAGLAHS, Bldg 115/CURE 11301 Wilshire Blvd, Los Angeles, CA 90073, USA. emayer@ucla.edu
Bradesi
Sylvie
S
D002243:Carbolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D011358:Product Surveillance, Postmarketing; D011788:Quality of Life; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D002243:Carbolines; D005765:Gastrointestinal Agents; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C090840:alosetron