2,3,4,5-Tetrahydro-5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1H-pyrido[4,3-b]indol-1-one hydrochloride Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Alosetron was launched in March 2000 in the US as a new oral treatment for diarrheapredominant
irritable bowel syndrome in women. This structurally-related analog of
ondansetron is prepared by alkylation of the pyrido[4,3-b]indol-1-one skeleton with the
appropriate trityl-protected chloromethylimidazole. Although its mechanism of action is not
fully understood, alosetron is known to be a potent and selective 5-HT
3 antagonist with a
superior pharmacodynamic profile than its predecessor ondansetron. Besides being
present in the central nervous system, 5-HT
3 receptors are located on neurons of both
enteric and sensory nervous systems. Alosetron may act on several of these sites leading
to the regulation of intestinal secretion, gastrointestinal contractility and gastric emptying.
Clinically, it has been found that a twice-daily dose of Img of alosetron not only improves
bowel function, stool frequency and stool consistency but also affects the pain severity and
sense of urgency in IBS. Despite its short half-life (1.5h) and extensive metabolism (at
least 12 metabolites have been identified in urine), alosetron shows a long duration (10h)
of inhibition of the serotonin-induced skin flare response in man. Due to reported cases of
constipation and ischemic colitis as well as rare fatalities of patients under treatment with
Lotronex, Glaxo-Wellcome withdrew the drug from the US market in November and is
currently running further clinical trials.
Originator
Glaxo-Wellcome (UK)
Trademarks
Lotronex
2,3,4,5-Tetrahydro-5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1H-pyrido[4,3-b]indol-1-one hydrochloride Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
