PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
astemizole

2D structure

Overview

Trade Names: Alermizol; Astemisan; Astemisol; Astemison; Hismanal; Histamen; Histaminos; Histazol; Kelp; Laridal; Metodik; Nono-Nastizol A; Paralergin; Retolen; Waruzol
PharmGKB Accession Id: PA448498

Description

A long-acting, non-sedative antihistamine, a highly selective histamine1-receptor antagonist with minimal central and anticholinergic effects
[PMID:2892659]. It has been withdrawn from the market because of the risk of drug-induced long QT syndrome and fatal Torsades de Pointes [PMID:14999113] (source: PharmGKB)

Indication

For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. (source: Drug Bank)

ATC Therapeutic Category

  • R06AX:Other antihistamines for systemic use

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Astemizole competes with histamine for binding at H<sub>1</sub>-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H<sub>1</sub>-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier and preferentially binds at H1 receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H<sub>3</sub>-receptors, producing adverse effects. (source: Drug Bank)

Pharmacology

A long-acting, non-sedative antihistamine, a highly selective histamine1-receptor antagonist with minimal central and anticholinergic effects
[PMID:2892659] (source: PharmGKB)

Food Interactions

Take on an empty stomach, food decreases absorption by 60%. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Almost completely metabolized in the liver and primarily excreted in the feces. (source: Drug Bank)

Protein Binding

96.7% (source: Drug Bank)

Absorption

Rapidly absorbed from the gastrointestinal tract. (source: Drug Bank)

Toxicity

LD<sub>50</sub>=2052mg/kg in mice (source: Drug Bank)

Isomeric SMILES Code:

COc1ccc(cc1)CCN2CCC(CC2)Nc3nc4ccccc4n3Cc5ccc(cc5)F (source: Drug Bank)

In-Depth Annotations (In-Depth Annotation)

  1. rs890293 at chr1:60165082 in CYP2J2
    Although this promoter SNP is the most-studied CYP2J2 variant, its in vivo effects remain unclear due to conflicting experimental findings.
    Variant Name:
    CYP2J2*7, CYP2J2:G-50T, CYP2J2:G-76T
    Related Drugs:
    astemizole, diclofenac, terfenadine
    Related Diseases:
    Asthma, Brain Ischemia, Coronary Artery Disease, Coronary Disease, Coronary Stenosis, Essential hypertension, Hypertension
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Has annotations
CYP2J2
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
KCNH2
  • CO
  • PD
  •   
  • FA
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
HRH1 Uncurated Annotation (source: Drug Bank)
KCNH2 Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
amprenavir Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
aprepitant Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
bepridil Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
cimetidine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clarithromycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
delavirdine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
efavirenz Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
erythromycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
fluoxetine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
fluvoxamine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
fosamprenavir Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
grepafloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
indinavir Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
itraconazole Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
josamycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
ketoconazole Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mesoridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mibefradil Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nefazodone Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nelfinavir Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
posaconazole Uncurated Annotation Contraindicated co-administration (source: Drug Bank)
quinine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
quinupristin Uncurated Annotation This combination presents an increased risk of toxicity (source: Drug Bank)
ritonavir Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
saquinavir Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
sparfloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
telithromycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
troleandomycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
voriconazole Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Acquired Long QT Syndrome (aLQTS)
  • CO
  • PD
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Long QT Syndrome
  • CO
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Torsades de Pointes
  • CO
  • PD
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00637
KEGG Compound ID:
C06832
KEGG Drug ID:
D00234
PubChem Compound ID:
2247
PubChem Substance ID:
188751
IUPHAR Ligand ID:
2603

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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