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
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)
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 |
DescriptionSources: https://www.drugs.com/mtm/astemizole.html
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 The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.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
Sources: https://ichapps.com/Drug/view/astemizole
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6124876
Curator's Comment: # Janssen Pharmaceuticals
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21944853 |
8.68 null [pKi] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | HISMANAL Approved UseFor the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. Launch Date4.73212813E11 |
|||
Primary | HISMANAL Approved UseFor the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. Launch Date4.73212813E11 |
Cmax
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 |
T1/2
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 |
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) Sources: Bundle branch block right (serious) QT interval prolonged (serious) |
740 mg single, oral Overdose |
healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: M Population Size: 1 Sources: |
Other AEs: Arrhythmia ventricular... |
30 mg single, oral Overdose |
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) Sources: Arrhythmia ventricular (serious) Heart block atrioventricular (serious) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Bundle branch block right | serious | 6 mg/kg single, oral Overdose |
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 |
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 |
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 |
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 |
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 |
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 |
healthy, 4 years n = 1 Health Status: healthy Age Group: 4 years Sex: M Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 2.73 uM] | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
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 |
|
[Effects of clinically available drugs on the repolarization process of the heart assessed by the in vivo canine models]. | 2003 Jun |
|
Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study. | 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 |
|
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 |
|
Comparison of alamar blue and MTT assays for high through-put screening. | 2004 Oct |
|
QT PRODACT: in vivo QT assay with a conscious monkey for assessment of the potential for drug-induced QT interval prolongation. | 2005 |
|
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 |
|
In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine. | 2005 Aug 18 |
|
Treatment for allergic rhinitis and chronic idiopathic urticaria: focus on oral antihistamines. | 2005 Dec |
|
Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen. | 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 |
|
A case of pheniramine dependence. | 2005 Mar |
|
Identifying modulators of hERG channel activity using the PatchXpress planar patch clamp. | 2005 Mar |
|
Effect of trazodone on hERG channel current and QT-interval. | 2005 Mar 7 |
|
[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 |
|
Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein. | 2006 Apr |
|
A clinical drug library screen identifies astemizole as an antimalarial agent. | 2006 Aug |
|
A lingering mistake. | 2006 Feb 28 |
|
Life-threatening bradyarrhythmia after massive azithromycin overdose. | 2006 Jan |
|
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
Sample Use Guides
In Vivo Use Guide
Sources: https://ichapps.com/Drug/view/astemizole
10 mg once daily, should be taken on an empty stomach
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21944853
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
Edited
Wed Jul 05 23:23:45 UTC 2023
by
admin
on
Wed Jul 05 23:23:45 UTC 2023
|
Record UNII |
7HU6337315
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
WHO-ATC |
R06AX11
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
||
|
WHO-VATC |
QR06AX11
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
||
|
NCI_THESAURUS |
C29578
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
100000086629
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
DTXSID9020110
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
68844-77-9
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
249
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
ASTEMIZOLE
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
272-441-9
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
CHEMBL296419
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
6799
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
4755
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
759570
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
M2116
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | Merck Index | ||
|
C28834
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
329963
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
SUB05586MIG
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
2247
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
42328
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | RxNorm | ||
|
DB00637
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
7HU6337315
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
2896
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
D016589
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY | |||
|
2603
Created by
admin on Wed Jul 05 23:23:46 UTC 2023 , Edited by admin on Wed Jul 05 23:23:46 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
TARGET -> INHIBITOR | |||
|
OFF-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 |
|
|
|||