Alosetron is an antagonist of the serotonin (5-HT) receptor subtype 5-HT3 (Kis = 0.3 and 0.4 nM for the rat cortical and human recombinant receptors, respectively).1 It is selective for 5-HT3 over 5-HT2 and 5-HT1A receptors (Kis = 6.3 and >100 ?M, respectively), as well as α1-, β1-, and β2- adrenergic, M1, M2, and M3 muscarinic, GABAA, dopamine D2, and nicotinic receptors at 10 μM.2 Alosetron (0.3-10 nM) inhibits 5-HT-induced depolarization of isolated rat vagus nerve.1 It reduces wrap restraint stress-induced defecation and the number of abdominal muscle contractions in a rat model of irritable bowel syndrome with diarrhea (IBS-D) when administered at a dose of 0.1 mg/kg.3 Formulations containing alosetron have been used in the treatment of diarrhea-predominant irritable bowel syndrome in women.
1.Humphrey, P.P., Bountra, C., Clayton, N., et al.Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndromeAilment Pharmacol. Ther.13(Suppl 2)31-38(1999) 2.Kilpatrick, G.J., Hagan, R.M., Butler, A., et al.GR68755, a potent and selective antagonist of 5-HT3 receptorsGlaxo Grp. Res. Ltd.259P(1991) 3.Taquichi, R., Shilkata, K., Furuya, Y., et al.Selective corticotropin-releasing factor 1 receptor antagonist E2508 reduces restraint stress-induced defecation and visceral pain in rat modelsPsychoneuroendocrinology75110-115(2017)