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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Astemizole
- Accession Number
- DB00637 (APRD00585)
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Description
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 It was withdrawn from market by the manufacturer in 1999 due to the potential to cause arrhythmias at high doses, especially when when taken with CYP inhibitors or grapefruit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.
- Structure
Structure for DB00637 (Astemizole)
- Synonyms
- 1-(P-Fluorobenzyl)-2-((1-(2-(P-methoxyphenyl)ethyl)piperid-4-yl)amino)benzimidazole
- 1-(P-Fluorobenzyl)-2-((1-(P-methoxyphenethyl)-4-piperidyl)amino)benzimidazole
- Astemison
- Astemizol
- Astémizole
- Astemizolum
- External IDs
- BRN 4830190 / R 43,512 / R43512 / UNII-7HU6337315
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Hismanal - Tab 10mg Tablet 10 mg Oral Johnson & Johnson Merck Consumer Pharmaceuticals Of Canada 1997-01-21 1999-03-04 Canada 
Hismanal Suspension 2mg/ml Suspension 2 mg Oral Janssen Pharmaceutica, Division Of Janssen Ortho Inc. 1984-12-31 1997-08-12 Canada Hismanal Tab 10mg Tablet 10 mg Oral Janssen Pharmaceutica, Division Of Janssen Ortho Inc. 1984-12-31 1997-08-12 Canada - International/Other Brands
- Acemiz (Lupin) / Alerkin (Incobra) / Astesen (Senosiain) / Hismanal (Janssen) / Histalong (Biofarma) / Lergibrumizol (Bruluart) / Stemiz (Cadila HC)
- Categories
- Anti-Allergic Agents
- Antihistamines for Systemic Use
- Benzimidazoles
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Histamine Agents
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine H1 Antagonists, Non-Sedating
- Neurotransmitter Agents
- P-glycoprotein/ABCB1 Inhibitors
- QTc Prolonging Agents
- UNII
- 7HU6337315
- CAS number
- 68844-77-9
- Weight
- Average: 458.5703
Monoisotopic: 458.248189839 - Chemical Formula
- C28H31FN4O
- InChI Key
- GXDALQBWZGODGZ-UHFFFAOYSA-N
- InChI
- InChI=1S/C28H31FN4O/c1-34-25-12-8-21(9-13-25)14-17-32-18-15-24(16-19-32)30-28-31-26-4-2-3-5-27(26)33(28)20-22-6-10-23(29)11-7-22/h2-13,24H,14-20H2,1H3,(H,30,31)
- IUPAC Name
- 1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-1,3-benzodiazol-2-amine
- SMILES
- COC1=CC=C(CCN2CCC(CC2)NC2=NC3=CC=CC=C3N2CC2=CC=C(F)C=C2)C=C1
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.
- 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.
Target Actions Organism AHistamine H1 receptor antagonistHuman UPotassium voltage-gated channel subfamily H member 2 inhibitorHuman UPotassium voltage-gated channel subfamily H member 1 Not Available Human UMicrotubule-associated protein tau Not Available Human - 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.
- 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
Pathway Category Astemizole H1-Antihistamine Action Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group 2,5-Dimethoxy-4-ethylamphetamine 2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Astemizole. Experimental, Illicit 2,5-Dimethoxy-4-ethylthioamphetamine 2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Astemizole. Experimental 3,4-Methylenedioxyamphetamine 3,4-Methylenedioxyamphetamine may decrease the sedative activities of Astemizole. Experimental, Illicit 4-Bromo-2,5-dimethoxyamphetamine 4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Astemizole. Experimental, Illicit Abiraterone The serum concentration of Astemizole can be increased when it is combined with Abiraterone. Approved Acetyl sulfisoxazole The metabolism of Astemizole can be decreased when combined with Acetyl sulfisoxazole. Approved, Vet Approved Afatinib The serum concentration of Afatinib can be increased when it is combined with Astemizole. Approved Amiodarone The serum concentration of Astemizole can be increased when it is combined with Amiodarone. Approved, Investigational Amphetamine Amphetamine may decrease the sedative activities of Astemizole. Approved, Illicit, Investigational Apalutamide The serum concentration of Astemizole can be decreased when it is combined with Apalutamide. Approved, Investigational Aprepitant The serum concentration of Astemizole can be increased when it is combined with Aprepitant. Approved, Investigational Artemether The metabolism of Astemizole can be decreased when combined with Artemether. Approved Asunaprevir The serum concentration of Asunaprevir can be increased when it is combined with Astemizole. Approved, Investigational, Withdrawn Atazanavir The serum concentration of Astemizole can be increased when it is combined with Atazanavir. Approved, Investigational Atomoxetine The metabolism of Astemizole can be decreased when combined with Atomoxetine. Approved Atorvastatin The risk or severity of adverse effects can be increased when Astemizole is combined with Atorvastatin. Approved Benzphetamine Benzphetamine may decrease the sedative activities of Astemizole. Approved, Illicit Benzylpenicilloyl Polylysine Astemizole may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent. Approved Betahistine The therapeutic efficacy of Betahistine can be decreased when used in combination with Astemizole. Approved, Investigational Betaxolol The metabolism of Astemizole can be decreased when combined with Betaxolol. Approved, Investigational Bicalutamide The serum concentration of Astemizole can be increased when it is combined with Bicalutamide. Approved Boceprevir The serum concentration of Astemizole can be increased when it is combined with Boceprevir. Approved, Withdrawn Bortezomib The metabolism of Astemizole can be decreased when combined with Bortezomib. Approved, Investigational Bosentan The serum concentration of Astemizole can be decreased when it is combined with Bosentan. Approved, Investigational Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Astemizole. Approved Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Astemizole. Approved, Investigational Bromocriptine The risk or severity of adverse effects can be increased when Bromocriptine is combined with Astemizole. Approved, Investigational Bupropion The metabolism of Astemizole can be decreased when combined with Bupropion. Approved Cabergoline The risk or severity of adverse effects can be increased when Cabergoline is combined with Astemizole. Approved Carbamazepine The metabolism of Astemizole can be increased when combined with Carbamazepine. Approved, Investigational Celecoxib The metabolism of Astemizole can be decreased when combined with Celecoxib. Approved, Investigational Ceritinib The serum concentration of Astemizole can be increased when it is combined with Ceritinib. Approved Cerivastatin The serum concentration of Cerivastatin can be increased when it is combined with Astemizole. Approved, Withdrawn Chloroquine The metabolism of Astemizole can be decreased when combined with Chloroquine. Approved, Investigational, Vet Approved Chlorphentermine Chlorphentermine may decrease the sedative activities of Astemizole. Illicit, Withdrawn Chlorpromazine The metabolism of Astemizole can be decreased when combined with Chlorpromazine. Approved, Investigational, Vet Approved Cholecalciferol The metabolism of Astemizole can be decreased when combined with Cholecalciferol. Approved, Nutraceutical Cimetidine The metabolism of Astemizole can be decreased when combined with Cimetidine. Approved, Investigational Cinacalcet The metabolism of Astemizole can be decreased when combined with Cinacalcet. Approved Citalopram The metabolism of Astemizole can be decreased when combined with Citalopram. Approved Clarithromycin The serum concentration of Astemizole can be increased when it is combined with Clarithromycin. Approved Clemastine The metabolism of Astemizole can be decreased when combined with Clemastine. Approved, Investigational Clobazam The metabolism of Astemizole can be decreased when combined with Clobazam. Approved, Illicit Clomipramine The metabolism of Astemizole can be decreased when combined with Clomipramine. Approved, Investigational, Vet Approved Clotrimazole The metabolism of Astemizole can be decreased when combined with Clotrimazole. Approved, Vet Approved Clozapine The metabolism of Astemizole can be decreased when combined with Clozapine. Approved Cobicistat The serum concentration of Astemizole can be increased when it is combined with Cobicistat. Approved Cocaine The metabolism of Astemizole can be decreased when combined with Cocaine. Approved, Illicit Colchicine The serum concentration of Colchicine can be increased when it is combined with Astemizole. Approved Conivaptan The serum concentration of Conivaptan can be increased when it is combined with Astemizole. Approved, Investigational Crizotinib The metabolism of Astemizole can be decreased when combined with Crizotinib. Approved Curcumin The serum concentration of Astemizole can be increased when it is combined with Curcumin. Approved, Investigational Cyclosporine The metabolism of Astemizole can be decreased when combined with Cyclosporine. Approved, Investigational, Vet Approved Dabigatran etexilate The serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Astemizole. Approved Dabrafenib The serum concentration of Astemizole can be decreased when it is combined with Dabrafenib. Approved, Investigational Darifenacin The metabolism of Astemizole can be decreased when combined with Darifenacin. Approved, Investigational Darunavir The serum concentration of Astemizole can be increased when it is combined with Darunavir. Approved Dasatinib The serum concentration of Astemizole can be increased when it is combined with Dasatinib. Approved, Investigational Deferasirox The serum concentration of Astemizole can be decreased when it is combined with Deferasirox. Approved, Investigational Delamanid Astemizole may increase the QTc-prolonging activities of Delamanid. Approved, Investigational Delavirdine Delavirdine may increase the arrhythmogenic activities of Astemizole. Approved Desipramine The metabolism of Astemizole can be decreased when combined with Desipramine. Approved, Investigational Deutetrabenazine Astemizole may increase the QTc-prolonging activities of Deutetrabenazine. Approved, Investigational Dextroamphetamine Dextroamphetamine may decrease the sedative activities of Astemizole. Approved, Illicit Diethylpropion Diethylpropion may decrease the sedative activities of Astemizole. Approved, Illicit Dihydroergocornine The risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Astemizole. Approved Dihydroergocristine The risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Astemizole. Approved, Experimental Dihydroergocryptine The risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Astemizole. Experimental Dihydroergotamine The risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Astemizole. Approved, Investigational Diltiazem The metabolism of Astemizole can be decreased when combined with Diltiazem. Approved, Investigational Diphenhydramine The metabolism of Astemizole can be decreased when combined with Diphenhydramine. Approved, Investigational Dosulepin The metabolism of Astemizole can be decreased when combined with Dosulepin. Approved Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Astemizole. Approved, Investigational Doxycycline The metabolism of Astemizole can be decreased when combined with Doxycycline. Approved, Investigational, Vet Approved Dronedarone The metabolism of Astemizole can be decreased when combined with Dronedarone. Approved Duloxetine The metabolism of Astemizole can be decreased when combined with Duloxetine. Approved Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Astemizole. Approved Eliglustat The metabolism of Astemizole can be decreased when combined with Eliglustat. Approved Enzalutamide The serum concentration of Astemizole can be decreased when it is combined with Enzalutamide. Approved Ergonovine The risk or severity of adverse effects can be increased when Ergonovine is combined with Astemizole. Approved Ergotamine The risk or severity of adverse effects can be increased when Ergotamine is combined with Astemizole. Approved Erythromycin The metabolism of Astemizole can be decreased when combined with Erythromycin. Approved, Investigational, Vet Approved Everolimus The serum concentration of Everolimus can be increased when it is combined with Astemizole. Approved Fluconazole The metabolism of Astemizole can be decreased when combined with Fluconazole. Approved, Investigational Fluoxetine The metabolism of Astemizole can be decreased when combined with Fluoxetine. Approved, Vet Approved Fluvastatin The serum concentration of Fluvastatin can be increased when it is combined with Astemizole. Approved Fluvoxamine The metabolism of Astemizole can be decreased when combined with Fluvoxamine. Approved, Investigational Fosamprenavir The metabolism of Astemizole can be decreased when combined with Fosamprenavir. Approved Fosaprepitant The serum concentration of Astemizole can be increased when it is combined with Fosaprepitant. Approved Fosphenytoin The metabolism of Astemizole can be increased when combined with Fosphenytoin. Approved, Investigational Fusidic Acid The serum concentration of Astemizole can be increased when it is combined with Fusidic Acid. Approved, Investigational Gepefrine Gepefrine may decrease the sedative activities of Astemizole. Experimental Haloperidol The metabolism of Astemizole can be decreased when combined with Haloperidol. Approved Hyaluronidase The therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Astemizole. Approved, Investigational Hydroxyamphetamine Hydroxyamphetamine may decrease the sedative activities of Astemizole. Approved Ibrutinib The serum concentration of Ibrutinib can be increased when it is combined with Astemizole. Approved Idelalisib The serum concentration of Astemizole can be increased when it is combined with Idelalisib. Approved Imatinib The metabolism of Astemizole can be decreased when combined with Imatinib. Approved Imipramine The metabolism of Astemizole can be decreased when combined with Imipramine. Approved Indinavir The serum concentration of Astemizole can be increased when it is combined with Indinavir. Approved Iofetamine I-123 Iofetamine I-123 may decrease the sedative activities of Astemizole. Approved Isavuconazole The serum concentration of Astemizole can be increased when it is combined with Isavuconazole. Approved, Investigational Isavuconazonium The metabolism of Astemizole can be decreased when combined with Isavuconazonium. Approved, Investigational Isoniazid The metabolism of Astemizole can be decreased when combined with Isoniazid. Approved, Investigational Isradipine The metabolism of Astemizole can be decreased when combined with Isradipine. Approved, Investigational Itraconazole The serum concentration of Astemizole can be increased when it is combined with Itraconazole. Approved, Investigational Ivacaftor The serum concentration of Astemizole can be increased when it is combined with Ivacaftor. Approved Ketoconazole Ketoconazole may increase the QTc-prolonging activities of Astemizole. Approved, Investigational Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Astemizole. Approved Lisdexamfetamine Lisdexamfetamine may decrease the sedative activities of Astemizole. Approved, Investigational Lisuride The risk or severity of adverse effects can be increased when Lisuride is combined with Astemizole. Approved, Investigational Lopinavir The serum concentration of Astemizole can be increased when it is combined with Lopinavir. Approved Lorcaserin The metabolism of Astemizole can be decreased when combined with Lorcaserin. Approved Lorpiprazole The serum concentration of Astemizole can be increased when it is combined with Lorpiprazole. Approved Lovastatin The serum concentration of Lovastatin can be increased when it is combined with Astemizole. Approved, Investigational Luliconazole The serum concentration of Astemizole can be increased when it is combined with Luliconazole. Approved Lumacaftor The metabolism of Astemizole can be increased when combined with Lumacaftor. Approved Lumefantrine The metabolism of Astemizole can be decreased when combined with Lumefantrine. Approved Lysergic Acid Diethylamide The risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Astemizole. Illicit, Investigational, Withdrawn Macimorelin Astemizole may increase the QTc-prolonging activities of Macimorelin. Approved, Investigational Manidipine The metabolism of Astemizole can be decreased when combined with Manidipine. Approved, Investigational Mephedrone Mephedrone may decrease the sedative activities of Astemizole. Investigational Mephentermine Mephentermine may decrease the sedative activities of Astemizole. Approved Metergoline The risk or severity of adverse effects can be increased when Metergoline is combined with Astemizole. Experimental Methadone The metabolism of Astemizole can be decreased when combined with Methadone. Approved Methamphetamine Methamphetamine may decrease the sedative activities of Astemizole. Approved, Illicit Methotrimeprazine The metabolism of Astemizole can be decreased when combined with Methotrimeprazine. Approved, Investigational Methoxyphenamine Methoxyphenamine may decrease the sedative activities of Astemizole. Experimental Methylergometrine The risk or severity of adverse effects can be increased when Methylergometrine is combined with Astemizole. Approved Methysergide The risk or severity of adverse effects can be increased when Methysergide is combined with Astemizole. Approved Metoprolol The metabolism of Astemizole can be decreased when combined with Metoprolol. Approved, Investigational Mevastatin The serum concentration of Mevastatin can be increased when it is combined with Astemizole. Experimental Midomafetamine Midomafetamine may decrease the sedative activities of Astemizole. Experimental, Illicit, Investigational Midostaurin The metabolism of Astemizole can be decreased when combined with Midostaurin. Approved, Investigational Mifepristone The serum concentration of Astemizole can be increased when it is combined with Mifepristone. Approved, Investigational Mirabegron The metabolism of Astemizole can be decreased when combined with Mirabegron. Approved Mitotane The serum concentration of Astemizole can be decreased when it is combined with Mitotane. Approved MMDA MMDA may decrease the sedative activities of Astemizole. Experimental, Illicit Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Astemizole. Approved Nefazodone The serum concentration of Astemizole can be increased when it is combined with Nefazodone. Approved, Withdrawn Nelfinavir The serum concentration of Astemizole can be increased when it is combined with Nelfinavir. Approved Netupitant The serum concentration of Astemizole can be increased when it is combined with Netupitant. Approved, Investigational Nevirapine The metabolism of Astemizole can be increased when combined with Nevirapine. Approved Nicardipine The metabolism of Astemizole can be decreased when combined with Nicardipine. Approved, Investigational Nicergoline The risk or severity of adverse effects can be increased when Nicergoline is combined with Astemizole. Approved, Investigational Nilotinib The metabolism of Astemizole can be decreased when combined with Nilotinib. Approved, Investigational Nintedanib The serum concentration of Nintedanib can be increased when it is combined with Astemizole. Approved Olaparib The metabolism of Astemizole can be decreased when combined with Olaparib. Approved Osimertinib The serum concentration of Astemizole can be increased when it is combined with Osimertinib. Approved Palbociclib The serum concentration of Astemizole can be increased when it is combined with Palbociclib. Approved, Investigational Panobinostat The serum concentration of Astemizole can be increased when it is combined with Panobinostat. Approved, Investigational Paroxetine The metabolism of Astemizole can be decreased when combined with Paroxetine. Approved, Investigational Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Astemizole. Approved Peginterferon alfa-2b The serum concentration of Astemizole can be decreased when it is combined with Peginterferon alfa-2b. Approved Pentobarbital The metabolism of Astemizole can be increased when combined with Pentobarbital. Approved, Investigational, Vet Approved Pergolide The risk or severity of adverse effects can be increased when Pergolide is combined with Astemizole. Approved, Investigational, Vet Approved, Withdrawn Phenobarbital The metabolism of Astemizole can be increased when combined with Phenobarbital. Approved, Investigational Phentermine Phentermine may decrease the sedative activities of Astemizole. Approved, Illicit Phenytoin The metabolism of Astemizole can be increased when combined with Phenytoin. Approved, Vet Approved Pitavastatin The serum concentration of Pitavastatin can be increased when it is combined with Astemizole. Approved Pitolisant The serum concentration of Astemizole can be decreased when it is combined with Pitolisant. Approved, Investigational Posaconazole The serum concentration of Astemizole can be increased when it is combined with Posaconazole. Approved, Investigational, Vet Approved Pravastatin The serum concentration of Pravastatin can be increased when it is combined with Astemizole. Approved Primidone The metabolism of Astemizole can be increased when combined with Primidone. Approved, Vet Approved Promazine The metabolism of Astemizole can be decreased when combined with Promazine. Approved, Vet Approved Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Astemizole. Approved Pseudoephedrine Pseudoephedrine may decrease the sedative activities of Astemizole. Approved Quinidine The metabolism of Astemizole can be decreased when combined with Quinidine. Approved, Investigational Quinine The metabolism of Astemizole can be decreased when combined with Quinine. Approved Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Astemizole. Approved, Investigational Ribociclib The risk or severity of QTc prolongation can be increased when Ribociclib is combined with Astemizole. Approved, Investigational Rifabutin The metabolism of Astemizole can be increased when combined with Rifabutin. Approved, Investigational Rifampicin The metabolism of Astemizole can be increased when combined with Rifampicin. Approved Rifapentine The metabolism of Astemizole can be increased when combined with Rifapentine. Approved, Investigational Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Astemizole. Approved, Investigational Rilpivirine The serum concentration of Rilpivirine can be increased when it is combined with Astemizole. Approved Ritobegron Ritobegron may decrease the sedative activities of Astemizole. Investigational Ritonavir The metabolism of Astemizole can be decreased when combined with Ritonavir. Approved, Investigational Rolapitant The metabolism of Astemizole can be decreased when combined with Rolapitant. Approved, Investigational Ropinirole The metabolism of Astemizole can be decreased when combined with Ropinirole. Approved, Investigational Rosuvastatin The serum concentration of Rosuvastatin can be increased when it is combined with Astemizole. Approved Rucaparib The metabolism of Astemizole can be decreased when combined with Rucaparib. Approved, Investigational Saquinavir The serum concentration of Astemizole can be increased when it is combined with Saquinavir. Approved, Investigational Sarilumab The therapeutic efficacy of Astemizole can be decreased when used in combination with Sarilumab. Approved, Investigational Sertraline The metabolism of Astemizole can be decreased when combined with Sertraline. Approved Sildenafil The metabolism of Astemizole can be decreased when combined with Sildenafil. Approved, Investigational Silodosin The serum concentration of Silodosin can be increased when it is combined with Astemizole. Approved Siltuximab The serum concentration of Astemizole can be decreased when it is combined with Siltuximab. Approved, Investigational Simeprevir The serum concentration of Astemizole can be increased when it is combined with Simeprevir. Approved Simvastatin The serum concentration of Simvastatin can be increased when it is combined with Astemizole. Approved St. John's Wort The serum concentration of Astemizole can be decreased when it is combined with St. John's Wort. Approved, Investigational, Nutraceutical Stiripentol The serum concentration of Astemizole can be increased when it is combined with Stiripentol. Approved Sulfisoxazole The metabolism of Astemizole can be decreased when combined with Sulfisoxazole. Approved, Vet Approved Telaprevir The serum concentration of Astemizole can be increased when it is combined with Telaprevir. Approved, Withdrawn Telithromycin The serum concentration of Astemizole can be increased when it is combined with Telithromycin. Approved Terbinafine The metabolism of Astemizole can be decreased when combined with Terbinafine. Approved, Investigational, Vet Approved Terguride The risk or severity of adverse effects can be increased when Terguride is combined with Astemizole. Experimental Thioridazine The metabolism of Astemizole can be decreased when combined with Thioridazine. Approved, Withdrawn Ticlopidine The metabolism of Astemizole can be decreased when combined with Ticlopidine. Approved Tipranavir The metabolism of Astemizole can be decreased when combined with Tipranavir. Approved, Investigational Tocilizumab The serum concentration of Astemizole can be decreased when it is combined with Tocilizumab. Approved Tolvaptan The serum concentration of Tolvaptan can be increased when it is combined with Astemizole. Approved Topotecan The serum concentration of Topotecan can be increased when it is combined with Astemizole. Approved, Investigational Tranylcypromine The metabolism of Astemizole can be decreased when combined with Tranylcypromine. Approved, Investigational Vemurafenib The serum concentration of Astemizole can be decreased when it is combined with Vemurafenib. Approved Venlafaxine The metabolism of Astemizole can be decreased when combined with Venlafaxine. Approved Verapamil The metabolism of Astemizole can be decreased when combined with Verapamil. Approved Vincristine The excretion of Vincristine can be decreased when combined with Astemizole. Approved, Investigational Voriconazole The serum concentration of Astemizole can be increased when it is combined with Voriconazole. Approved, Investigational Ziprasidone The metabolism of Astemizole can be decreased when combined with Ziprasidone. Approved - Food Interactions
- Take on an empty stomach, food decreases absorption by 60%.
References
- Synthesis Reference
Godelieve Irma Christine Maria Heylen, Cornelus Gerardus Maria Janssen, Jurzak Mirek, Henricus Petrus Martinus Maria Van Assouw, "Radiolabeled astemizole and method of making." U.S. Patent US07541476, issued June 02, 2009.
US07541476- General References
- 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:16723379]
- 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:16816845]
- External Links
- Human Metabolome Database
- HMDB0014775
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- Astemizole
- ATC Codes
- R06AX11 — Astemizole
- MSDS
- Download (57.2 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Tablet Oral 10 mg Suspension Oral 2 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 149.1 °C PhysProp water solubility 432 mg/L Not Available logP 5.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0012 mg/mL 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 Å2 ChemAxon Rotatable Bond Count 8 ChemAxon Refractivity 135.64 m3·mol-1 ChemAxon Polarizability 52.08 Å3 ChemAxon Number of Rings 5 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.765 Caco-2 permeable + 0.5217 P-glycoprotein substrate Substrate 0.8162 P-glycoprotein inhibitor I Inhibitor 0.8563 P-glycoprotein inhibitor II Inhibitor 0.8995 Renal organic cation transporter Inhibitor 0.7708 CYP450 2C9 substrate Non-substrate 0.8732 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.6777 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.5127 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9096 Ames test Non AMES toxic 0.6444 Carcinogenicity Non-carcinogens 0.9553 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.2847 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.9267 hERG inhibition (predictor II) Inhibitor 0.8575
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzimidazoles
- Sub Class
- Not Available
- Direct Parent
- Benzimidazoles
- Alternative Parents
- Phenethylamines / Anisoles / Methoxybenzenes / Phenoxy compounds / Alkyl aryl ethers / Fluorobenzenes / Aralkylamines / N-substituted imidazoles / Aryl fluorides / Piperidines show 6 more
- Substituents
- Benzimidazole / Phenethylamine / Anisole / Phenoxy compound / Phenol ether / Methoxybenzene / Alkyl aryl ether / Fluorobenzene / Halobenzene / Aralkylamine show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- piperidines, benzimidazoles (CHEBI:2896)
Targets
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Histamine receptor activity
- Specific Function
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- Salata JJ, Jurkiewicz NK, Wallace AA, Stupienski RF 3rd, Guinosso PJ Jr, Lynch JJ Jr: Cardiac electrophysiological actions of the histamine H1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine. Circ Res. 1995 Jan;76(1):110-9. [PubMed:8001268]
- Howarth PH, Emanuel MB, Holgate ST: Astemizole, a potent histamine H1-receptor antagonist: effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin weal responses and relationship to serum levels. Br J Clin Pharmacol. 1984 Jul;18(1):1-8. [PubMed:6146346]
- Kaliner MA, Check WA: Non-sedating antihistamines. Allergy Proc. 1988 Nov-Dec;9(6):649-63. [PubMed:3147222]
- Cavero I, Mestre M, Guillon JM, Heuillet E, Roach AG: Preclinical in vitro cardiac electrophysiology: a method of predicting arrhythmogenic potential of antihistamines in humans? Drug Saf. 1999;21 Suppl 1:19-31; discussion 81-7. [PubMed:10597865]
- Llenas J, Cardelus I, Heredia A, de Mora F, Gristwood RW: Cardiotoxicity of histamine and the possible role of histamine in the arrhythmogenesis produced by certain antihistamines. Drug Saf. 1999;21 Suppl 1:33-8; discussion 81-7. [PubMed:10597866]
- Richards DM, Brogden RN, Heel RC, Speight TM, Avery GS: Astemizole. A review of its pharmacodynamic properties and therapeutic efficacy. Drugs. 1984 Jul;28(1):38-61. [PubMed:6204835]
- Krstenansky PM, Cluxton RJ Jr: Astemizole: a long-acting, nonsedating antihistamine. Drug Intell Clin Pharm. 1987 Dec;21(12):947-53. [PubMed:2892659]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- Zhou Z, Vorperian VR, Gong Q, Zhang S, January CT: Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J Cardiovasc Electrophysiol. 1999 Jun;10(6):836-43. [PubMed:10376921]
- Chachin M, Katayama Y, Yamada M, Horio Y, Ohmura T, Kitagawa H, Uchida S, Kurachi Y: Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel. Eur J Pharmacol. 1999 Jun 25;374(3):457-60. [PubMed:10422790]
- Taglialatela M, Castaldo P, Pannaccione A, Giorgio G, Genovese A, Marone G, Annunziato L: Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity. Clin Exp Allergy. 1999 Jul;29 Suppl 3:182-9. [PubMed:10444235]
- Grzelewska-Rzymowska I, Pietrzkowicz M, Gorska M: [The effect of second generation histamine antagonists on the heart]. Pneumonol Alergol Pol. 2001;69(3-4):217-26. [PubMed:11575008]
- Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [PubMed:15272206]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- General Function
- Phosphorelay sensor kinase activity
- Specific Function
- Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:22732247). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (By sim...
- Gene Name
- KCNH1
- Uniprot ID
- O95259
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 1
- Molecular Weight
- 111421.76 Da
References
- Garcia-Ferreiro RE, Kerschensteiner D, Major F, Monje F, Stuhmer W, Pardo LA: Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J Gen Physiol. 2004 Oct;124(4):301-17. Epub 2004 Sep 13. [PubMed:15365094]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- General Function
- Structural constituent of cytoskeleton
- Specific Function
- Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neu...
- Gene Name
- MAPT
- Uniprot ID
- P10636
- Uniprot Name
- Microtubule-associated protein tau
- Molecular Weight
- 78927.025 Da
References
- Rojo LE, Alzate-Morales J, Saavedra IN, Davies P, Maccioni RB: Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease. J Alzheimers Dis. 2010;19(2):573-89. doi: 10.3233/JAD-2010-1262. [PubMed:20110603]
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [PubMed:10597902]
- 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. [PubMed:11259984]
- Cvetkovic RS, Goa KL: Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802. [PubMed:12662125]
- 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. [PubMed:15133245]
- 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. [PubMed:15684493]
- 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. [PubMed:10592235]
- 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
References
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Transporters
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
- Ishikawa M, Fujita R, Takayanagi M, Takayanagi Y, Sasaki K: Reversal of acquired resistance to doxorubicin in K562 human leukemia cells by astemizole. Biol Pharm Bull. 2000 Jan;23(1):112-5. [PubMed:10706423]
Drug created on June 13, 2005 07:24 / Updated on June 02, 2018 06:38