U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of ASTEMIZOLE

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

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

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 The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.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

Curator's Comment: Astemizole is a second generation H1-receptor antagonist. It does not cross the BBB significantly due to this reason do not cause CNS depression or drowsiness at normal doses.

Originator

Curator's Comment: # Janssen Pharmaceuticals

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
8.68 null [pKi]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
HISMANAL

Approved Use

For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.

Launch Date

1984
Primary
HISMANAL

Approved Use

For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.

Launch Date

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.1 mg/L
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
260 mg × h/L
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
223 h
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
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

Doses

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

AEs

AESignificanceDosePopulation
Bundle branch block right serious
6 mg/kg single, oral
Overdose
Dose: 6 mg/kg
Route: oral
Route: single
Dose: 6 mg/kg
Sources:
healthy, 1.5 years
n = 1
Health Status: healthy
Age Group: 1.5 years
Population Size: 1
Sources:
QT interval prolonged serious
6 mg/kg single, oral
Overdose
Dose: 6 mg/kg
Route: oral
Route: single
Dose: 6 mg/kg
Sources:
healthy, 1.5 years
n = 1
Health Status: healthy
Age Group: 1.5 years
Population Size: 1
Sources:
Ventricular tachycardia serious
6 mg/kg single, oral
Overdose
Dose: 6 mg/kg
Route: oral
Route: single
Dose: 6 mg/kg
Sources:
healthy, 1.5 years
n = 1
Health Status: healthy
Age Group: 1.5 years
Population Size: 1
Sources:
Arrhythmia ventricular serious
740 mg single, oral
Overdose
Dose: 740 mg
Route: oral
Route: single
Dose: 740 mg
Sources:
healthy, 22 years
n = 1
Health Status: healthy
Age Group: 22 years
Sex: M
Population Size: 1
Sources:
Arrhythmia ventricular serious
30 mg single, oral
Overdose
Dose: 30 mg
Route: oral
Route: single
Dose: 30 mg
Sources:
healthy, 4 years
n = 1
Health Status: healthy
Age Group: 4 years
Sex: M
Population Size: 1
Sources:
Heart block atrioventricular serious
30 mg single, oral
Overdose
Dose: 30 mg
Route: oral
Route: single
Dose: 30 mg
Sources:
healthy, 4 years
n = 1
Health Status: healthy
Age Group: 4 years
Sex: M
Population Size: 1
Sources:
QT interval prolonged serious
30 mg single, oral
Overdose
Dose: 30 mg
Route: oral
Route: single
Dose: 30 mg
Sources:
healthy, 4 years
n = 1
Health Status: healthy
Age Group: 4 years
Sex: M
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 2.73 uM]
yes
Drug as victim
PubMed

PubMed

TitleDatePubMed
Human immunodeficiency virus-associated eosinophilic folliculitis. A unique dermatosis associated with advanced human immunodeficiency virus infection.
1991 Feb
Effect of astemizole on antigen-mediated histamine release from the blood of patients with allergic rhinitis.
1992 Dec
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
Emerging role of drug interaction studies in drug development: the good, the bad, and the unknown.
2001 Autumn
A case series of drug-induced long QT syndrome and Torsade de Pointes.
2001 Dec
Comparative effects of maternal prenatal and postnatal exposures to astemizole on reproductive parameters of rats.
2002 Mar-Apr
[Risk of drug interactions. Combinations of drugs associated with ventricular arrhythmias].
2002 May-Jun
Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole.
2002 Nov
Lopinavir/ritonavir: a review of its use in the management of HIV infection.
2003
Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis.
2003 Apr
Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice.
2003 Aug
Gateways to clinical trials.
2003 Dec
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.
2003 Dec 15
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
Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG.
2003 Jun 27
Detection of proarrhythmia in the female rabbit heart: blinded validation.
2003 Mar
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
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
Antihistamines.
2003 Sep-Oct
Quinolone safety and efficacy more important than potency.
2004 Jan
Gateways to clinical trials.
2004 Jan-Feb
Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.
2004 Jul
Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression.
2004 Jul
Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity.
2004 May
QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates.
2004 May-Jun
Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.
2004 Oct
Mechanism of block of hEag1 K+ channels by imipramine and astemizole.
2004 Oct
Comparison of alamar blue and MTT assays for high through-put screening.
2004 Oct
QT PRODACT: in vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals.
2005
Digital drug discovery.
2005
Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs.
2005
Molecular cloning and kinetic characterization of an aldehyde dehydrogenase gene in Klebsiella pneumoniae.
2005 Apr
Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity.
2005 Feb
Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen.
2005 Feb
[Torsades de pointes caused by cetirizine overdose].
2005 Feb
Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants.
2005 Feb
Effect of histamine receptor antagonists on aminophylline-induced seizures and lethality in mice.
2005 Jul-Aug
Estimation of potency of HERG channel blockers: impact of voltage protocol and temperature.
2005 Jul-Aug
Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers.
2005 Jun
Effect of trazodone on hERG channel current and QT-interval.
2005 Mar 7
Generalized lichen nitidus.
2005 Mar-Apr
[Efficacy and safety of astemizole in the treatment of allergic rhinitis and urticaria: a systematic review with meta-analysis].
2005 May-Jun
Grape fruit juice-drug interactions.
2005 Oct
Histamine H1 antagonists block M-currents in dissociated rat cortical neurons.
2005 Sep 28
A clinical drug library screen identifies astemizole as an antimalarial agent.
2006 Aug
Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway.
2006 Jul
In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation.
2006 Jul
An extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) system for grading of diabetic macular edema in the Astemizole Retinopathy Trial.
2006 Jun
A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy.
2006 May 10
H1 histamine receptor antagonists induce genotoxic and caspase-2-dependent apoptosis in human melanoma cells.
2006 Sep
Patents

Patents

Sample Use Guides

In Vivo Use Guide
10 mg once daily, should be taken on an empty stomach
Route of Administration: Oral
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 Fri Dec 15 15:55:26 GMT 2023
Edited
by admin
on Fri Dec 15 15:55:26 GMT 2023
Record UNII
7HU6337315
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ASTEMIZOLE
HSDB   INN   JAN   MART.   MI   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
WHO-VATC QR06AX11
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
Code System Code Type Description
SMS_ID
100000086629
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
EPA CompTox
DTXSID9020110
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
CAS
68844-77-9
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
DRUG CENTRAL
249
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
WIKIPEDIA
ASTEMIZOLE
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
ECHA (EC/EINECS)
272-441-9
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
ChEMBL
CHEMBL296419
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
HSDB
6799
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
INN
4755
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
NSC
759570
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
MERCK INDEX
m2116
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C28834
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
NSC
329963
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
EVMPD
SUB05586MIG
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
PUBCHEM
2247
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
RXCUI
42328
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY RxNorm
DRUG BANK
DB00637
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
FDA UNII
7HU6337315
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
CHEBI
2896
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
MESH
D016589
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
IUPHAR
2603
Created by admin on Fri Dec 15 15:55:26 GMT 2023 , Edited by admin on Fri Dec 15 15:55:26 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
OFF-TARGET->INHIBITOR
BINDING
IC50
TARGET -> INHIBITOR
BINDING
IC50
TARGET -> INHIBITOR
BIOSIMILAR -> PARENT
BINDING
Related Record Type Details
METABOLITE ACTIVE -> PARENT
It retains antihistamine prop- erties, has a long elimination time of 9 to 13 days, and its steady-state serum concentration exceeds that of astemizole by more than 30-foId.
MAJOR
PLASMA
METABOLITE ACTIVE -> PARENT
MINOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC