Alosetron (Lotronex) is a synthetic, potent and selective antagonist of the 5-HT3A and 5-HT3B channels. Alosetron has an effective concentration of 10 nM -10 μM and a Ki of 0.29±0.031 nmol/L for the human 5-HT3 receptor. Alosetron has a relatively short t0.5 of 180 minutes when dissociating from the human 5-HT receptor. Alosetron was found to significantly reduce restrained stress induced defecation in rats and is used as second line therapy for women with severe diarrhea predominant irritable bowel (IBS-D). In these patients Alosetron is effective in reducing abdominal pain and diarrhea compared to placebo treatment. Alosetron is rapidly absorbed after oral administration with a mean bioavailability of 50-60% and a plasma protein binding level of about 82%. Despite its beneficial effect, Alosetron can cause ischemic colitis and severe constipation (0.95 and 0.36/1000 patient years respectably) and therefore it is currently administered under a risk-management program in the United-States only.
