ASTEMIZOLE

US Previously Marketed

First approved in 1988

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H31FN4O
Molecular Weight	458.5703
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(CCN2CCC(CC2)NC3=NC4=CC=CC=C4N3CC5=CC=C(F)C=C5)C=C1

InChI

InChIKey=GXDALQBWZGODGZ-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/mtm/astemizole.html

Astemizole is antihistamine drug, discovered by Janssen Pharmaceutical and used to prevent sneezing, runny nose, itching and watering of the eyes, and other allergic symptoms. The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21944853	Antagonist 2778		8.68 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Seasonal allergic rhinitis 64 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. Launch Date 4.73212813E11
Chronic idiopathic urticaria 11 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. Launch Date 4.73212813E11

C_max

Value	Dose	Co-administered	Analyte	Population
2.1 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10423595	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		DESMETHYLASTEMIZOLE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.9 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10423595	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		ASTEMIZOLE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
260 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10423595	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		DESMETHYLASTEMIZOLE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28.4 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10423595	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		ASTEMIZOLE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
223 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10423595	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		DESMETHYLASTEMIZOLE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10423595	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		ASTEMIZOLE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
6 mg/kg single, oral Overdose Dose: 6 mg/kg Route: oral Route: single Dose: 6 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 1.5 years n = 1 Health Status: healthy Age Group: 1.5 years Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	Other AEs: Ventricular tachycardia, Bundle branch block right... Other AEs: Ventricular tachycardia (serious) Bundle branch block right (serious) QT interval prolonged (serious) Sources: https://pubmed.ncbi.nlm.nih.gov/1578320
740 mg single, oral Overdose Dose: 740 mg Route: oral Route: single Dose: 740 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8189766	healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/8189766	Other AEs: Arrhythmia ventricular... Other AEs: Arrhythmia ventricular (serious) Sources: https://pubmed.ncbi.nlm.nih.gov/8189766
30 mg single, oral Overdose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 4 years n = 1 Health Status: healthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	Other AEs: QT interval prolonged, Arrhythmia ventricular... Other AEs: QT interval prolonged (serious) Arrhythmia ventricular (serious) Heart block atrioventricular (serious) Sources: https://pubmed.ncbi.nlm.nih.gov/1578320

AEs

AE	Significance	Dose	Population
Bundle branch block right	serious	6 mg/kg single, oral Overdose Dose: 6 mg/kg Route: oral Route: single Dose: 6 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 1.5 years n = 1 Health Status: healthy Age Group: 1.5 years Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320
QT interval prolonged	serious	6 mg/kg single, oral Overdose Dose: 6 mg/kg Route: oral Route: single Dose: 6 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 1.5 years n = 1 Health Status: healthy Age Group: 1.5 years Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320
Ventricular tachycardia	serious	6 mg/kg single, oral Overdose Dose: 6 mg/kg Route: oral Route: single Dose: 6 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 1.5 years n = 1 Health Status: healthy Age Group: 1.5 years Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320
Arrhythmia ventricular	serious	740 mg single, oral Overdose Dose: 740 mg Route: oral Route: single Dose: 740 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8189766	healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/8189766
Arrhythmia ventricular	serious	30 mg single, oral Overdose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 4 years n = 1 Health Status: healthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320
Heart block atrioventricular	serious	30 mg single, oral Overdose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 4 years n = 1 Health Status: healthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320
QT interval prolonged	serious	30 mg single, oral Overdose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1578320	healthy, 4 years n = 1 Health Status: healthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1578320

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699	CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C18 138 CYP2C19 991 CYP2E1 667 CYP4A11 119 UGT 192 CYP2J2 56

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16406207/	yes [IC50 2.73 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17616561/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C18 138	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP4A11 119	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	yes
CYP2J2 56	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26899760/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	yes
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2896	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2896
ChemicalBook	CB6741448	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6741448
MolPort	MolPort-003-666-765	https://www.molport.com/shop/molecule-link/MolPort-003-666-765
ZINC	ZINC000000601274	http://zinc15.docking.org/substances/ZINC000000601274
eMolecules	534476	https://www.emolecules.com/cgi-bin/more?vid=534476

PubMed

Title	Date	PubMed
Human immunodeficiency virus-associated eosinophilic folliculitis. A unique dermatosis associated with advanced human immunodeficiency virus infection.	1991 Feb	1671328
Effect of astemizole on antigen-mediated histamine release from the blood of patients with allergic rhinitis.	1992 Dec	1283658
Canine in vivo tracheal chemotaxis of eosinophils to antigen in sensitized dogs: inhibition by a steroid, a systemic lazaroid U-78517F, and several topical H1 antihistamines.	1992 Sep	1355641
Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis.	2003 Apr	12704356
Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice.	2003 Aug	13679230
Gateways to clinical trials.	2003 Dec	14735233
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.	2003 Dec 15	14678746
In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver.	2003 Jun	12851038
Understanding the structure-activity relationship of the human ether-a-go-go-related gene cardiac K+ channel. A model for bad behavior.	2003 May 22	12747773
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003 Nov 17	14612892
Antihistamines.	2003 Sep-Oct	12954920
Quinolone safety and efficacy more important than potency.	2004 Jan	15112647
Gateways to clinical trials.	2004 Jan-Feb	14988742
Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.	2004 Jul	15272206
Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression.	2004 Jul	14985237
Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity.	2004 May	15133245
QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates.	2004 May-Jun	15211616
Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.	2004 Oct	15671647
Mechanism of block of hEag1 K+ channels by imipramine and astemizole.	2004 Oct	15365094
Comparison of alamar blue and MTT assays for high through-put screening.	2004 Oct	15251189
QT PRODACT: in vivo QT assay with a conscious monkey for assessment of the potential for drug-induced QT interval prolongation.	2005	16493189
QT PRODACT: in vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals.	2005	16493187
Digital drug discovery.	2005	16207366
Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs.	2005	15762770
Molecular cloning and kinetic characterization of an aldehyde dehydrogenase gene in Klebsiella pneumoniae.	2005 Apr	15909058
In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine.	2005 Aug 18	16109168
Treatment for allergic rhinitis and chronic idiopathic urticaria: focus on oral antihistamines.	2005 Dec	16278258
Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity.	2005 Feb	15861034
Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen.	2005 Feb	15798395
[Torsades de pointes caused by cetirizine overdose].	2005 Feb	15787309
Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants.	2005 Feb	15684493
Effect of histamine receptor antagonists on aminophylline-induced seizures and lethality in mice.	2005 Jul-Aug	16129921
Estimation of potency of HERG channel blockers: impact of voltage protocol and temperature.	2005 Jul-Aug	15936218
Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers.	2005 Jun	15889300
A case of pheniramine dependence.	2005 Mar	16492663
Identifying modulators of hERG channel activity using the PatchXpress planar patch clamp.	2005 Mar	15799960
Effect of trazodone on hERG channel current and QT-interval.	2005 Mar 7	15740727
Generalized lichen nitidus.	2005 Mar-Apr	15804308
[Efficacy and safety of astemizole in the treatment of allergic rhinitis and urticaria: a systematic review with meta-analysis].	2005 May-Jun	16158785
Grape fruit juice-drug interactions.	2005 Oct	16380358
Histamine H1 antagonists block M-currents in dissociated rat cortical neurons.	2005 Sep 28	16125149
Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein.	2006 Apr	16406207
A clinical drug library screen identifies astemizole as an antimalarial agent.	2006 Aug	16816845
A lingering mistake.	2006 Feb 28	16505473
Life-threatening bradyarrhythmia after massive azithromycin overdose.	2006 Jan	16506357
Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway.	2006 Jul	16723379
In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation.	2006 Jul	16489111
An extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) system for grading of diabetic macular edema in the Astemizole Retinopathy Trial.	2006 Jun	16769613
A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy.	2006 May 10	16686951
H1 histamine receptor antagonists induce genotoxic and caspase-2-dependent apoptosis in human melanoma cells.	2006 Sep	16569656

Patents

Sample Use Guides

In Vivo Use Guide

10 mg once daily, should be taken on an empty stomach

Route of Administration: Oral

In Vitro Use Guide

Affinity at histamine H1 receptor was measured in Sf9 cells transfected with H1 and coexpressing Regulator Of G-Protein Signaling 4 (RGS4). [3H]Mepyramine was used a radiolabel in a competition binding assay. pKi of astemizole was 8.68.

Name

Type

Language

ASTEMIZOLE

Official Name

English

Astemizole [WHO-DD]

Common Name

English

ASTEMIZOLE [USAN]

Common Name

English

ASTEMIZOLE [MI]

Common Name

English

astemizole [INN]

Common Name

English

ASTEMIZOLE [USP IMPURITY]

Common Name

English

1-(P-FLUOROBENZYL)-2-((1-(P-METHOXYPHENETHYL)-4-PIPERIDYL)AMINO)BENZIMIDAZOLE

Common Name

English

ASTEMIZOLE [JAN]

Common Name

English

ASTEMIZOLE [VANDF]

Common Name

English

NSC-329963

Code

English

R 43,512

Code

English

ASTEMIZOLE [HSDB]

Common Name

English

1H-BENZIMIDAZOL-2-AMINE, 1-((4-FLUOROPHENYL)METHYL)-N-(1-(2-(4-METHOXYPHENYL)ETHYL)-4-PIPERIDINYL)-

Systematic Name

English

ASTEMIZOLE [MART.]

Common Name

English

NSC-759570

Code

English

Classification Tree Code System Code

WHO-ATC

R06AX11