Alosetron is clinically effective in alleviating pain and bowel-related symptoms in female patients with certain types of irritable bowel syndrome (IBS), according to a study in the Lancet (2000;355:1035). In addition, alosetron is well tolerated, say Professor Michael Camilleri (gastrointestinal research unit, Mayo clinic, Rochester, US) and colleagues.
In a study of 647 female patients with diarrhoea-predominant or alternating IBS, 324 patients were assigned 1mg alosetron twice daily and 323 patients were given placebo. Alosetron was found to provide adequate pain relief over a three-month period in 41 per cent of patients compared with 29 per cent of the placebo-treated group. Alosetron significantly decreased urgency and stool frequency and increased stool firmness, Professor Camilleri and colleagues say. However, there was a greater occurrence of constipation in the alosetron group (30 per cent of patients compared with 3 per cent in the placebo group). No serious adverse effects were reported during the study. The benefits of alosetron started after between one and two weeks of therapy, and persisted for the three month duration of the study. The authors note that they only studied women because the beneficial effects of alosetron have been shown more consistently in women than men. In addition, about 70 per cent of patients with IBS who present to physicians in western countries are women.
Alosteron is a type 3 serotonin receptor (5HT3) antagonist, Professor Camilleri and colleagues say. The authors explain that this class of drugs increases the threshold for sensation and discomfort during distension of the rectum. Such drugs also increase colonic compliance, slow colonic transit and improve stool consistency.
Alosetron has been launched in the US under the brand name Lotronex. A spokesman for its manufacturer, Glaxo Wellcome, told The Journal on March 27 that alosetron would be launched in the UK at the end of this year.
New therapies for IBS are discussed by Dr Tony Lembo (department of medicine, Harvard Medical School, US) in an editorial accompanying the study (Lancet 2000;355:1030). "Recently developed therapies for IBS have focused on the modulation of neurotransmitters in the ‘brain-gut' axis." While the 5HT3 antagonist, alosetron, was the furthest advanced, other therapies in earlier stages of development included a partial 5HT4 agonist, a 5HT4 agonist, a cholecystokinin-A antagonist and a dopamine-2 antagonist, he says.
In the editorial, Dr Lembo explains how 5HT3 antagonists work. IBS patients have lower visceral pain thresholds than healthy people, he says. 5HT lowers visceral pain thresholds by stimulating extrinsic enteric sensory nerves and the predominant receptor on such nerves is 5HT3. Hence, selective 5HT3 antagonists (such as alosetron) increase visceral pain thresholds.