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QuickView for Astemizole (compound)

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PubChem

PubChem Compound 2247

Name:	Astemizole
PubChem Compound ID:	2247
Description:	A long-acting, non-sedative antihistaminic used in the treatment of seasonal allergic rhinitis, asthma, allergic conjunctivitis, and chronic idiopathic urticaria. The drug is well tolerated and has no anticholinergic side effects.
Molecular formula:	C₂₈H₃₁FN₄O
Molecular weight:	458.571 g/mol
Synonyms:	R-43512; EINECS 272-441-9; Histamen; 68844-77-9; KBio1_000039; D00234; nchembio732-comp2; Prestwick_35; UPCMLD-DP024:001; CCRIS 7595. show more » R-43512; EINECS 272-441-9; Histamen; 68844-77-9; KBio1_000039; D00234; nchembio732-comp2; Prestwick_35; UPCMLD-DP024:001; CCRIS 7595; KBioGR_001686; Novo-mastizol A; KBio2_000928; Astemizol [INN-Spanish]; NSC329963; SPBio_002151; Astemizole (JAN/USP); KBioSS_000928; Spectrum2_001732; Spectrum4_001223; 1-(p-Fluorobenzyl)-2-((1-(2-(p-methoxyphenyl)ethyl)piperid-4-yl)amino)benzimidazole; Hismanal (TN); CAS-68844-77-9; MJD-30; Spectrum_000448; Prestwick0_000136; Astemizole [USAN:BAN:INN]; KBio2_006064; 1H-Benzimidazol-2-amine, 1-((4-fluorophenyl)methyl)-N-(1-(2-(4-methoxyphenyl)eth l)-4-piperidinyl)-; MLS000028667; R 42512; Astemizol [German]; KBio3_001904; nchembio806-comp1; Astemizole; SMR000058911; BRN 4830190; 1-((4-Fluorophenyl)methyl)-N-(1-(2-(4-methoxyphenyl)ethyl)-4-piperidinyl)- 1H-benzimidazol-2-amine; Astemizolum [INN-Latin]; Laridal; Benzimidazole, 1-(p-fluorobenzyl)-2-((1-(2-(p-methoxyphenyl)ethyl)piperid-4-yl)amino)-; Spectrum3_001072; 1-(p-Fluorobenzyl)-2-((1-(p-methoxyphenethyl)-4-piperidyl)amino)benzimidazole; Histaminos; Kelp; Metodih; Paralergin; 1H-Benzimidazol-2-amine, 1-((4-fluorophenyl)methyl)-N-(1-(2-(4-methoxyphenyl)ethyl)-4-piperidinyl)-; DivK1c_000039; Hestazol; 1H-Benzimidazol-2-amine, 1-[(4-fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-; Wareezol; Retolen; Alermizol; KBio2_003496; Astemison; SPBio_001804; NCGC00016913-01; NINDS_000039; LS-32978; Prestwick1_000136; HSDB 6799; C06832; Hismanal show less «

DrugBank

Identification

Name:	Astemizole
Name (isomeric):	DB00637
Drug Type:	small molecule
Description:	A long-acting, non-sedative antihistaminic used in the treatment of seasonal allergic rhinitis, asthma, allergic conjunctivitis, and chronic idiopathic urticaria. The drug is well tolerated and has no anticholinergic side effects.
Brand:	Waruzol, Paralergin, Kelp, Astemisol, Astemison, Metodik, Alermizol, Hismanal, Histamen, Nono-Nastizol A, Histazol, Laridal, Histaminos, Retolen, Astemisan
Category:	Antihistamines, Anti-Allergic Agents, Histamine H1 Antagonists, Non-Sedating
CAS number:	68844-77-9

Pharmacology

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.
Pharmacology:	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-br... show more » 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. show less «
Absorption:	Rapidly absorbed from the gastrointestinal tract.
Protein binding:	96.7%
Biotransformation:	Almost completely metabolized in the liver and primarily excreted in the feces.
Half Life:	1 day
Toxicity:	LD₅₀=2052mg/kg in mice
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take on an empty stomach, food decreases absorption by 60%.

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Fosamprenavir	Increased risk of cardiotoxicity and arrhythmias
Erythromycin	Increased risk of cardiotoxicity and arrhythmias
Telithromycin	Increased risk of cardiotoxicity and arrhythmias
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias

Targets

Histamine H1 receptor

Potassium voltage-gated channel subfamily H member 2

Enzymes

Cytochrome P450 3A4

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID:

P08684

Gene:

CYP3A4

Actions:

substrate, inhibitor

References:

Flockhart DA. "Drug Interactions: Cytochrome P450 Drug Interaction Table":http://medicine.iupui.edu/clinpharm/ddis/table.asp. Indiana University School of Medicine (2007). Accessed May 28, 2010.

Sweta N. Parikh, et al. Microsomes: Characterization and Inter-Individual Variability Among Donors. "Source":http://www.bdbiosciences.com/discovery_labware/gentest/products/pdf/P450_UDP_Carb.pdf

Nicolas JM, Whomsley R, Collart P, Roba J: In vitro inhibition of human liver drug metabolizing enzymes by second generation antihistamines. Chem Biol Interact. 1999 Nov 15;123(1):63-79.
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Matsumoto S, Yamazoe Y: Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine. Br J Clin Pharmacol. 2001 Feb;51(2):133-42.
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Cvetkovic RS, Goa KL: Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802.
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Goto A, Adachi Y, Inaba A, Nakajima H, Kobayashi H, Sakai K: Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity. Biol Pharm Bull. 2004 May;27(5):684-90.
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Goto A, Ueda K, Inaba A, Nakajima H, Kobayashi H, Sakai K: Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants. Biol Pharm Bull. 2005 Feb;28(2):328-34.
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Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
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Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24.
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Transporters

Multidrug resistance protein 1