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药品详细

Alosetron(阿洛司琼)

化学结构式图
中文名
阿洛司琼
英文名
Alosetron
分子式
C17H18N4O
化学名
5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1H,2H,3H,4H,5H-pyrido[4,3-b]indol-1-one
分子量
Average: 294.351
Monoisotopic: 294.148061218
CAS号
122852-42-0
ATC分类
A03A Drugs for Functional Bowel Disorders
药物类型
small molecule
阶段
approved, withdrawn
商品名
同义名
基本介绍

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 Alosetron was voluntarily withdrawn from the US market in November 2000 by the manufacturer due to numerous reports of severe adverse effects including ischemic colitis, severely obstructed or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.

生产厂家
  • Prometheus laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Andresen V, Hollerbach S: Reassessing the benefits and risks of alosetron: what is its place in the treatment of irritable bowel syndrome? Drug Saf. 2004;27(5):283-92. Pubmed
  2. Camilleri M: Pharmacology and clinical experience with alosetron. Expert Opin Investig Drugs. 2000 Jan;9(1):147-59. Pubmed
  3. Mayer EA, Bradesi S: Alosetron and irritable bowel syndrome. Expert Opin Pharmacother. 2003 Nov;4(11):2089-98. Pubmed
  4. Rahimi R, Nikfar S, Abdollahi M: Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials. Clin Ther. 2008 May;30(5):884-901. Pubmed
  5. Lewis JH: Alosetron for severe diarrhea-predominant irritable bowel syndrome: safety and efficacy in perspective. Expert Rev Gastroenterol Hepatol. 2010 Feb;4(1):13-29. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Indoles and Indole Derivatives
  • Lactams
Substructures
  • Indoles and Indole Derivatives
  • Amino Ketones
  • Pyrroles
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Imines
  • Cyanamides
适应症
药理
Indication 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.
Pharmacodynamics 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.
Absorption 50-60 %
Volume of distribution
  • 65 to 95 L
Protein binding 82%
Metabolism
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.
Half life 1.5 hours
Clearance
  • 600 mL/min
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 2 Not Available
Predicted Properties
Property Value Source
water solubility 4.38e-01 g/l ALOGPS
logP 1.85 ALOGPS
logP 1.21 ChemAxon
logS -2.8 ALOGPS
pKa (strongest acidic) 13.32 ChemAxon
pKa (strongest basic) 6.81 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 53.92 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 86.41 ChemAxon
polarizability 32.52 ChemAxon
药物相互作用
Drug Interaction
Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Alosetron by decreasing Alosetron metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Alosetron if Thiabendazole is initiated, discontinued or dose changed.
食物相互作用
  • Absorption is decreased by about 25% when taken with meals.
  • Take without regard to meals.

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