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 The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.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Seasonal allergic rhinitis 64 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.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 1984
Chronic idiopathic urticaria 11 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.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 1984

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
Effect of astemizole on antigen-mediated histamine release from the blood of patients with allergic rhinitis.	1992 Dec	1283658
Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole.	1999 Jun	10376921
Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel.	1999 Jun 25	10422790
Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects.	1999 Oct 29	10531299
Effect of oxatomide, an antiallergic agent, on QT interval in dogs.	2001	11799844
Safety of antihistamines in children.	2001	11235817
Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine.	2001 Feb	11259984
Influence of chronic treatment with H1 receptor antagonists on the anticonvulsant activity of antiepileptic drugs.	2001 Jan-Feb	11785920
Antihistamines and the torsade de point in children with allergic rhinitis.	2001 Jul-Aug	12067082
Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part II: Pharmacological profile.	2001 May	11334836
Recurrent syncope. Drug induced long QT syndrome.	2001 May	11320287
The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (HERG) mutations.	2002 Feb 15	11741928
Relationship between direct-to-consumer advertising and physician diagnosing and prescribing.	2002 Jan 1	11813466
Development of telemetry system in the common marmoset--cardiovascular effects of astemizole and nicardipine.	2002 May	12058448
Posttranslational modulation of glucocorticoid feedback inhibition at the pituitary level.	2002 Oct	12239090
Lopinavir/ritonavir: a review of its use in the management of HIV infection.	2003	12662125
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
Gateways to clinical trials.	2004 Jan-Feb	14988742
Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression.	2004 Jul	14985237
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
QT PRODACT: in vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals.	2005	16493187
Treatment for allergic rhinitis and chronic idiopathic urticaria: focus on oral antihistamines.	2005 Dec	16278258
[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
Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers.	2005 Jun	15889300
A lingering mistake.	2006 Feb 28	16505473

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