Overview
- Hirata, T. et al. (2007) J. Pharmacol. Sci. 104, 263.
Alomone Labs Alosetron hydrochloride blocks 5HT3A receptors expressed in HEK 293T cells.5-HT3A receptor currents were elicited with 10 µM 5-HT, delivered every 3 minutes. Alosetron hydrochloride (#A-236) was applied 30 seconds before stimulation at 1, 10 and 100 nM as indicated and completely inhibited the 5-HT induced current in a dose-dependent and reversible manner.
Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter synthesized from the amino acid tryptophan by the enzyme tryptophan-decarboxylase. The 5-HT3 channel is a ligand-gated ion channel receptor of the cys-loop channel family. It is a pentamer with five subunits surrounding a central channel1.
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 rats2 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 treatment3. Alosetron is rapidly absorbed after oral administration with a mean bioavailability of 50-60% and a plasma protein binding level of about 82%4. 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 only5.
