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 The drug was withdrawn from U.S. market in 1999 due to the potential to cause arrhythmias at high doses.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 |
---|---|---|
Effect of oxatomide, an antiallergic agent, on QT interval in dogs. | 2001 |
|
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 |
|
Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine. | 2001 Feb |
|
[Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs]. | 2001 Jun |
|
Pharmacokinetic and safety profile of desloratadine and fexofenadine when coadministered with azithromycin: a randomized, placebo-controlled, parallel-group study. | 2001 Mar |
|
Relationship between direct-to-consumer advertising and physician diagnosing and prescribing. | 2002 Jan 1 |
|
Next generation antihistamines: therapeutic rationale, accomplishments and advances. | 2002 Jun |
|
Lopinavir/ritonavir: a review of its use in the management of HIV infection. | 2003 |
|
Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice. | 2003 Aug |
|
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia. | 2003 Dec 15 |
|
Detection of proarrhythmia in the female rabbit heart: blinded validation. | 2003 Mar |
|
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 |
|
Mechanism of block of hEag1 K+ channels by imipramine and astemizole. | 2004 Oct |
|
QT PRODACT: in vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals. | 2005 |
|
Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen. | 2005 Feb |
|
Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers. | 2005 Jun |
|
Identifying modulators of hERG channel activity using the PatchXpress planar patch clamp. | 2005 Mar |
|
Generalized lichen nitidus. | 2005 Mar-Apr |
|
A clinical drug library screen identifies astemizole as an antimalarial agent. | 2006 Aug |
|
A lingering mistake. | 2006 Feb 28 |
|
An extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) system for grading of diabetic macular edema in the Astemizole Retinopathy Trial. | 2006 Jun |
|
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
Fri Dec 15 15:55:26 UTC 2023
by
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on
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Record UNII |
7HU6337315
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Record Status |
Validated (UNII)
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Record Version |
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WHO-ATC |
R06AX11
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QR06AX11
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NCI_THESAURUS |
C29578
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
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OFF-TARGET->INHIBITOR |
BINDING
IC50
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TARGET -> INHIBITOR |
BINDING
IC50
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TARGET -> INHIBITOR |
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BIOSIMILAR -> PARENT |
BINDING
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Related Record | Type | Details | ||
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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
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METABOLITE ACTIVE -> PARENT |
MINOR
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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