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药品详细

Astemizole(息斯敏)

化学结构式图
中文名
息斯敏
英文名
Astemizole
分子式
C28H31FN4O
化学名
1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-1,3-benzodiazol-2-amine
分子量
Average: 458.5703
Monoisotopic: 458.248189839
CAS号
68844-77-9
ATC分类
R06A 未知
药物类型
small molecule
阶段
approved, withdrawn
商品名
同义名
基本介绍

Astemizole is a long-acting, non-sedating second generation antihistamine used in the treatment of allergy symptoms. It was withdrawn from market by the manufacturer in 1999 due to the potential to cause arrhythmias at high doses, especially when when taken with CYP inhibitors or grapefruit juice.

生产厂家
    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. Wang X, Hockerman GH, Green HW 3rd, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL: Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway. FASEB J. 2006 Jul;20(9):1531-3. Epub 2006 May 24. Pubmed
    2. Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ Jr: A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol. 2006 Aug;2(8):415-6. Epub 2006 Jul 2. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes
    • Phenols and Derivatives
    • Benzimidazoles
    • Ethers
    • Phenethylamines
    • Anisoles
    Substructures
    • Aliphatic and Aryl Amines
    • Phenols and Derivatives
    • Benzimidazoles
    • Ethers
    • Benzene and Derivatives
    • Halobenzenes
    • Imidazoles
    • Phenethylamines
    • Heterocyclic compounds
    • Aromatic compounds
    • Anisoles
    • Cyanamides
    • Aryl Halides
    • Phenyl Esters
    • Piperidines
    适应症
    药理
    Indication Astemizole was indicated for use in the relieving allergy symptoms, particularly rhinitis and conjunctivitis. It has been withdrawn from the market however due to concerns of arrhythmias.
    Pharmacodynamics Astemizole is a second generation H1-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses.
    Mechanism of action Astemizole competes with histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H1-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier and preferentially binds at H1 receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H3-receptors, producing adverse effects.
    Absorption Rapidly absorbed from the gastrointestinal tract.
    Volume of distribution Not Available
    Protein binding 96.7%
    Metabolism
    Almost completely metabolized in the liver and primarily excreted in the feces.

    Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

    Substrate Enzymes Product
    Astemizole
    		desmethylastemizole Details
    Route of elimination Not Available
    Half life 1 day
    Clearance Not Available
    Toxicity LD50=2052mg/kg in mice
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 149.1 °C PhysProp
    water solubility 432 mg/L Not Available
    logP 5.8 Not Available
    Predicted Properties
    Property Value Source
    water solubility 1.20e-03 g/l ALOGPS
    logP 5.92 ALOGPS
    logP 5.39 ChemAxon
    logS -5.6 ALOGPS
    pKa (strongest basic) 8.75 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 4 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 42.32 ChemAxon
    rotatable bond count 8 ChemAxon
    refractivity 135.64 ChemAxon
    polarizability 52.08 ChemAxon
    药物相互作用
    Drug Interaction
    Amprenavir Increased risk of cardiotoxicity and arrhythmias
    Aprepitant Increased risk of cardiotoxicity and arrhythmias
    Bepridil Increased risk of cardiotoxicity and arrhythmias
    Cimetidine Increased risk of cardiotoxicity and arrhythmias
    Cisapride Increased risk of cardiotoxicity and arrhythmias
    Clarithromycin Increased risk of cardiotoxicity and arrhythmias
    Delavirdine Increased risk of cardiotoxicity and arrhythmias
    Efavirenz Increased risk of cardiotoxicity and arrhythmias
    Erythromycin Increased risk of cardiotoxicity and arrhythmias
    Fluoxetine Increased risk of cardiotoxicity and arrhythmias
    Fluvoxamine Increased risk of cardiotoxicity and arrhythmias
    Fosamprenavir Increased risk of cardiotoxicity and arrhythmias
    Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
    Indinavir Increased risk of cardiotoxicity and arrhythmias
    Itraconazole Increased risk of cardiotoxicity and arrhythmias
    Josamycin Increased risk of cardiotoxicity and arrhythmias
    Ketoconazole Increased risk of cardiotoxicity and arrhythmias
    Mesoridazine Increased risk of cardiotoxicity and arrhythmias
    Mibefradil Increased risk of cardiotoxicity and arrhythmias
    Nefazodone Increased risk of cardiotoxicity and arrhythmias
    Nelfinavir Increased risk of cardiotoxicity and arrhythmias
    Posaconazole Contraindicated co-administration
    Quinine Increased risk of cardiotoxicity and arrhythmias
    Quinupristin This combination presents an increased risk of toxicity
    Ritonavir Increased risk of cardiotoxicity and arrhythmias
    Saquinavir Increased risk of cardiotoxicity and arrhythmias
    Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
    Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
    Telithromycin Increased risk of cardiotoxicity and arrhythmias
    Thioridazine Increased risk of cardiotoxicity and arrhythmias
    Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Astemizole. Concomitant therapy is contraindicated.
    Troleandomycin Increased risk of cardiotoxicity and arrhythmias
    Voriconazole Increased risk of cardiotoxicity and arrhythmias
    食物相互作用
    • Take on an empty stomach, food decreases absorption by 60%.

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