Alosetron

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Alosetron
Systematic (IUPAC) name
5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]- 3,4-dihydro-2H-pyrido[4,3-b]indol-1(5H)-one
Identifiers
CAS number	122852-42-0
ATC code	A03AE01
PubChem	2099
DrugBank	APRD00580
Chemical data
Formula	C17H18N4O
Mol. mass	294.351 g/mol
Pharmacokinetic data
Bioavailability	50–60%
Protein binding	82%
Metabolism	Hepatic (including CYP2C9, CYP3A4 and CYP1A2)
Half life	1.5–1.7 hours
Excretion	Renal 73%, faecal 24%
Therapeutic considerations
Pregnancy cat.	B (U.S.)
Legal status	℞-only (U.S.)
Routes	Oral

Alosetron is a 5-HT₃ antagonist used for the management of severe diarrhoea-predominant irritable bowel syndrome (IBS) in women only. It was withdrawn from the market in 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, but was reintroduced in 2002 with availability and use restricted; it was the first drug ever returned to the U.S. market after withdrawal for safety concerns.^[1] It is currently marketed by GlaxoSmithKline under the trade name Lotronex.

Contents 1 Mode of action 2 Serious adverse effects 3 References 4 See also

[edit] Mode of action

Alosetron, while being a 5-HT₃ antagonist like ondansetron, is not an antiemetic. Alosetron has an antagonist action on the 5-HT₃ receptors of the enteric nervous system of the gastrointestinal tract.

[edit] Serious adverse effects

Alosetron was withdrawn in 2000 following the association of alosetron with serious life-threatening gastrointestinal adverse effects. The cumulative incidence of ischaemic colitis was 2 in 1000, while serious complications arising from constipation (obstruction, perforation, impaction, toxic megacolon, secondary colonic ischaemia, death) was 1 in 1000.^[2]

[edit] References

[edit] See also

• Irritable bowel syndrome

v • d • e Drugs for functional gastrointestinal disorders (A03) Drugs for functional bowel disorders antimuscarinics: Mebeverine - Dicycloverine - Propantheline papaverine and derivatives: Papaverine - Drotaverine - Moxaverine acting on serotonin receptors: 5-HT3 antagonists (Alosetron, Cilansetron) - 5HT4 agonists (Mosapride, Tegaserod) other: Diisopromine - Isometheptene - Phloroglucinol - Proglumide - Tridihexethyl Belladonna and derivatives (antimuscarinics) Atropine - Hyoscyamine - Butylscopolamine - Methylscopolamine - Scopolamine - Tincture of Belladonna Propulsives primarily dopamine antagonists (Metoclopramide/Bromopride, Domperidone, Alizapride) - serotonin agonists (Cisapride) - Clebopride