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

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 The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.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Seasonal allergic rhinitis 64 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.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Chronic idiopathic urticaria 11 Sources: http://www.druglib.com/activeingredient/astemizole/	Primary		Withdrawn	HISMANAL Approved Use For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.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
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
Second generation antihistamines in the treatment of seasonal allergic rhinitis due to Parietaria and cypress pollen.	2001 Dec	11735351
Influence of chronic treatment with H1 receptor antagonists on the anticonvulsant activity of antiepileptic drugs.	2001 Jan-Feb	11785920
Triamcinolone: new and old indications.	2001 Jul	11583068
Inhibition of depolarization-induced [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H(1) receptor antagonists through blockade of store-operated Ca(2+) channels (SOCs).	2001 Nov 1	11705456
The functional properties of the human ether-à-go-go-like (HELK2) K+ channel.	2002 Aug	12193184
Cardiotoxicity of new antihistamines and cisapride.	2002 Feb 28	12052668
Relationship between direct-to-consumer advertising and physician diagnosing and prescribing.	2002 Jan 1	11813466
Next generation antihistamines: therapeutic rationale, accomplishments and advances.	2002 Jun	12036424
Development of telemetry system in the common marmoset--cardiovascular effects of astemizole and nicardipine.	2002 May	12058448
Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole.	2002 Nov	12386130
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
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
Functional and pharmacological properties of canine ERG potassium channels.	2003 Jan	12388285
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
[Effects of clinically available drugs on the repolarization process of the heart assessed by the in vivo canine models].	2003 Jun	12835533
Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study.	2003 Jun	12789223
Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG.	2003 Jun 27	12775586
Detection of proarrhythmia in the female rabbit heart: blinded validation.	2003 Mar	12716112
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
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
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
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
Grape fruit juice-drug interactions.	2005 Oct	16380358
A clinical drug library screen identifies astemizole as an antimalarial agent.	2006 Aug	16816845
A lingering mistake.	2006 Feb 28	16505473
A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy.	2006 May 10	16686951

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

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