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=C(C=CC=C4)N3CC5=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

Molecular Formula	C28H31FN4O
Molecular Weight	458.5703
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.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 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21944853	Antagonist 2849		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Seasonal allergic rhinitis 64 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.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Chronic idiopathic urticaria 11 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.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
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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 Health Status: healthy Age Group: 1.5 years 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 Health Status: healthy Age Group: 22 years Sex: M 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 Health Status: healthy Age Group: 4 years Sex: M 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 Health Status: healthy Age Group: 1.5 years 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 Health Status: healthy Age Group: 1.5 years 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 Health Status: healthy Age Group: 1.5 years 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 Health Status: healthy Age Group: 22 years Sex: M 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 Health Status: healthy Age Group: 4 years Sex: M 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 Health Status: healthy Age Group: 4 years Sex: M 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 Health Status: healthy Age Group: 4 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/1578320

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910	CYP1A1 389 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C18 149 CYP2C19 1119 CYP2E1 729 CYP4A11 137 UGT 219 CYP2J2 71

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16406207/	yes [IC50 2.73 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17616561/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C18 149	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP4A11 137	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	yes
CYP2J2 71	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26899760/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259984/	yes
UGT 219	substrate 4014 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
eMolecules	534476	https://www.emolecules.com/cgi-bin/more?vid=534476
MolPort	MolPort-003-666-765	https://www.molport.com/shop/molecule-link/MolPort-003-666-765
ZINC	ZINC000000601274	http://zinc15.docking.org/substances/ZINC000000601274

PubMed

Title	Date	PubMed
H1 histamine receptor antagonists induce genotoxic and caspase-2-dependent apoptosis in human melanoma cells.	2006-09	16569656
A clinical drug library screen identifies astemizole as an antimalarial agent.	2006-08	16816845
Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway.	2006-07	16723379
In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation.	2006-07	16489111
An extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) system for grading of diabetic macular edema in the Astemizole Retinopathy Trial.	2006-06	16769613
A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy.	2006-05-10	16686951
Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein.	2006-04	16406207
A lingering mistake.	2006-02-28	16505473
Life-threatening bradyarrhythmia after massive azithromycin overdose.	2006-01	16506357
Treatment for allergic rhinitis and chronic idiopathic urticaria: focus on oral antihistamines.	2005-12	16278258
Grape fruit juice-drug interactions.	2005-10	16380358
Histamine H1 antagonists block M-currents in dissociated rat cortical neurons.	2005-09-28	16125149
[Efficacy and safety of astemizole in the treatment of allergic rhinitis and urticaria: a systematic review with meta-analysis].	2005-09-15	16158785
In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine.	2005-08-18	16109168
Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers.	2005-06	15889300
Generalized lichen nitidus.	2005-04-05	15804308
Molecular cloning and kinetic characterization of an aldehyde dehydrogenase gene in Klebsiella pneumoniae.	2005-04	15909058
Effect of trazodone on hERG channel current and QT-interval.	2005-03-07	15740727
Estimation of potency of HERG channel blockers: impact of voltage protocol and temperature.	2005-03-04	15936218
A case of pheniramine dependence.	2005-03	16492663
Identifying modulators of hERG channel activity using the PatchXpress planar patch clamp.	2005-03	15799960
Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity.	2005-02	15861034
Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen.	2005-02	15798395
[Torsades de pointes caused by cetirizine overdose].	2005-02	15787309
Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants.	2005-02	15684493
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
Effect of histamine receptor antagonists on aminophylline-induced seizures and lethality in mice.	2004-10-21	16129921
Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.	2004-10	15671647
Mechanism of block of hEag1 K+ channels by imipramine and astemizole.	2004-10	15365094
Comparison of alamar blue and MTT assays for high through-put screening.	2004-10	15251189
Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.	2004-07	15272206
Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression.	2004-07	14985237
QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates.	2004-06-24	15211616
Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity.	2004-05	15133245
Gateways to clinical trials.	2004-02-28	14988742
Quinolone safety and efficacy more important than potency.	2004-01	15112647
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.	2003-12-15	14678746
Gateways to clinical trials.	2003-12	14735233
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003-11-17	14612892
Antihistamines.	2003-09-05	12954920
Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice.	2003-08	13679230
In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver.	2003-06	12851038
[Effects of clinically available drugs on the repolarization process of the heart assessed by the in vivo canine models].	2003-06	12835533
Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study.	2003-06	12789223
Effect of astemizole on antigen-mediated histamine release from the blood of patients with allergic rhinitis.	1992-12	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.	1992-09	1355641
Human immunodeficiency virus-associated eosinophilic folliculitis. A unique dermatosis associated with advanced human immunodeficiency virus infection.	1991-02	1671328

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:13:23 GMT 2025` Edited by `admin` on `Mon Mar 31 18:13:23 GMT 2025`
Record UNII	7HU6337315
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ASTEMIZOLE

Official Name

English

NSC-329963

Preferred 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

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

CFR

21 CFR 216.24