Alosetron-New Drug for Irritable Bowel (cont.)
Since the underlying cause of IBS is unknown and, therefore, not treatable, the focus of treatment in IBS has been the management of symptoms. An assortment of drugs including antidepressants, anti-spasmotics (muscle-relaxers), anti-diarrheals, and laxatives have been used as well as dietary changes (e.g., high fiber, low fat). Psychiatric testing and treatment also has been employed.
Alosetron (Lotronex) is the first drug to be approved specifically for IBS. Two 12-week studies involved more than 1,200 women with IBS in whom diarrhea was a predominant symptom. The patients were treated for three months with either alosetron or placebo. Each week the patients were asked if the drug they were taking had given them adequate relief from abdominal pain and discomfort. Adequate monthly relief was defined as at least two weeks out of every four consecutive weeks with adequate relief. Forty-one percent of the patients receiving alosetron experienced adequate monthly relief for each of the three months (12 weeks) of the studies while only 30% of the patients receiving placebo experienced similar relief. Patients taking alosetron also had fewer days with a sense of urgency with their stools (decreasing from 7 out of every 10 days to 4 out of every 10 days), fewer daily stools (decreasing from three to two per day), and firmer stools. The most common side effect with alosetron, constipation, was seen in approximately one-third of patients and caused nine to ten out of every 100 patients to stop taking the drug either for a short time or indefinitely.
The exact mechanism by which alosetron relieves the symptoms of IBS is unknown. The discomfort and diarrhea of IBS are believed to be due to abnormal activity of the muscles of the intestines and/or the intestinal nerves that control the muscles. One of the chemical messengers which is important in coordinating the activity of intestinal nerves is serotonin. (Chemical messengers are chemicals produced and released by nerve cells that attach to receptors on nearby nerve cells and cause changes in the nearby nerve cells.) Alosetron belongs to a class of drugs that blocks one type of serotonin receptor called the 5-HT3 receptor. Serotonin and its receptors in the intestines are believed to control how pain is felt (sensation), contraction of intestinal muscle, and release of fluid into the intestines. These actions of serotonin can result in pain and diarrhea. The cause of IBS is unknown, but it is thought that stimuli such as food, medications, hormonal changes, or stress may trigger an excessive release of or an excessive response to serotonin. This may cause the pain and diarrhea that is seen in patients with diarrhea-predominent IBS. Alosetron, by blocking 5-HT3 receptors, reduces the actions of serotonin.