|Alosetron is a 5-HT3 antagonist used only for the management of severe diarrhoea-predominant irritable bowel syndrome (IBS) in women. Alosetron has an antagonist action on the 5-HT3 receptors and thus may modulate serotonin-sensitive gastrointestinal (GI) processes. Alosetron was voluntarily withdrawn from the US market in November 2000 by the manufacturer due to numerous reports of severe adverse effects including ischemic colitis, severely obstructed or ruptured bowel, and death. In June 2002, the FDA approved a supplemental new drug application allowing the remarketing of the drug under restricted conditions of use.
|Manufacturers||Prometheus laboratories inc
Prometheus Laboratories Inc.
Only for the treatment of symptoms of severe diarrhea-predominant irritable bowel syndrome (IBS) in women with chronic symptoms (generally lasting greater than 6 months) who does not present with anatomic or biochemical GI abnormalities and have not responded to conventional therapy.
Alosetron is a potent and selective antagonist of the serotonin 5-HT3
receptor type. Activation of these receptors and the resulting neuronal depolarization affects the regulation of visceral pain, colonic transit, and GI secretions processes that are related to IBS. By blocking these receptors, alosetron is able to effectively control IBS.
mechanism of action
Alosetron is a potent and selective 5-HT3
receptor antagonist. 5-HT3
receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). 5-HT3
receptor antagonists such as alosetron inhibit activation of non-selective cation channels which results in the modulation of serotonin-sensitive GI motor and sensory processes.
Hepatic, via microsomal cytochrome P450 (CYP)
route of elimination
Renal elimination of unchanged alosetron accounts for only 6% of the dose. Alosetron is extensively metabolized in humans.