Identification

Name
Astemizole
Accession Number
DB00637  (APRD00585)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Astemizole is a long-acting, non-sedating second generation antihistamine used in the treatment of allergy symptoms. It was withdrawn from market by the manufacturer in 1999 due to the potential to cause arrhythmias at high doses, especially when when taken with CYP inhibitors or grapefruit juice.

Structure
Thumb
Synonyms
  • 1-(P-Fluorobenzyl)-2-((1-(2-(P-methoxyphenyl)ethyl)piperid-4-yl)amino)benzimidazole
  • 1-(P-Fluorobenzyl)-2-((1-(P-methoxyphenethyl)-4-piperidyl)amino)benzimidazole
  • Astemison
  • Astemizol
  • Astémizole
  • Astemizolum
External IDs
BRN 4830190 / R 43,512 / R43512 / UNII-7HU6337315
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hismanal - Tab 10mgTablet10 mgOralJohnson & Johnson Merck Consumer Pharmaceuticals Of Canada1997-01-211999-03-04Canada
Hismanal Suspension 2mg/mlSuspension2 mgOralJanssen Pharmaceutica, Division Of Janssen Ortho Inc.1984-12-311997-08-12Canada
Hismanal Tab 10mgTablet10 mgOralJanssen Pharmaceutica, Division Of Janssen Ortho Inc.1984-12-311997-08-12Canada
International/Other Brands
Acemiz (Lupin) / Alerkin (Incobra) / Astesen (Senosiain) / Hismanal (Janssen) / Histalong (Biofarma) / Lergibrumizol (Bruluart) / Stemiz (Cadila HC)
Categories
UNII
7HU6337315
CAS number
68844-77-9
Weight
Average: 458.5703
Monoisotopic: 458.248189839
Chemical Formula
C28H31FN4O
InChI Key
GXDALQBWZGODGZ-UHFFFAOYSA-N
InChI
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)
IUPAC Name
1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-1,3-benzodiazol-2-amine
SMILES
COC1=CC=C(CCN2CCC(CC2)NC2=NC3=CC=CC=C3N2CC2=CC=C(F)C=C2)C=C1

Pharmacology

Indication

Astemizole was indicated for use in the relieving allergy symptoms, particularly rhinitis and conjunctivitis. It has been withdrawn from the market however due to concerns of arrhythmias.

Pharmacodynamics

Astemizole is a second generation H1-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses.

Mechanism of action

Astemizole competes with histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H1-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 H3-receptors, producing adverse effects.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 1Not AvailableHuman
UMicrotubule-associated protein tauNot AvailableHuman
Absorption

Rapidly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

96.7%

Metabolism

Almost completely metabolized in the liver and primarily excreted in the feces.

Route of elimination
Not Available
Half life

1 day

Clearance
Not Available
Toxicity

LD50=2052mg/kg in mice

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Astemizole H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Astemizole.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Astemizole.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Astemizole.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Astemizole.Experimental, Illicit
AbirateroneThe serum concentration of Astemizole can be increased when it is combined with Abiraterone.Approved
Acetyl sulfisoxazoleThe metabolism of Astemizole can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Astemizole.Approved
AmiodaroneThe serum concentration of Astemizole can be increased when it is combined with Amiodarone.Approved, Investigational
AmphetamineAmphetamine may decrease the sedative activities of Astemizole.Approved, Illicit, Investigational
ApalutamideThe serum concentration of Astemizole can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Astemizole can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Astemizole can be decreased when combined with Artemether.Approved
AsunaprevirThe serum concentration of Asunaprevir can be increased when it is combined with Astemizole.Approved, Investigational, Withdrawn
AtazanavirThe serum concentration of Astemizole can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Astemizole can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Astemizole is combined with Atorvastatin.Approved
BenzphetamineBenzphetamine may decrease the sedative activities of Astemizole.Approved, Illicit
Benzylpenicilloyl PolylysineAstemizole may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Astemizole.Approved, Investigational
BetaxololThe metabolism of Astemizole can be decreased when combined with Betaxolol.Approved, Investigational
BicalutamideThe serum concentration of Astemizole can be increased when it is combined with Bicalutamide.Approved
BoceprevirThe serum concentration of Astemizole can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Astemizole can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Astemizole can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Astemizole.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Astemizole.Approved, Investigational
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Astemizole.Approved, Investigational
BupropionThe metabolism of Astemizole can be decreased when combined with Bupropion.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Astemizole.Approved
CarbamazepineThe metabolism of Astemizole can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Astemizole can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Astemizole can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Astemizole.Approved, Withdrawn
ChloroquineThe metabolism of Astemizole can be decreased when combined with Chloroquine.Approved, Investigational, Vet Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Astemizole.Illicit, Withdrawn
ChlorpromazineThe metabolism of Astemizole can be decreased when combined with Chlorpromazine.Approved, Investigational, Vet Approved
CholecalciferolThe metabolism of Astemizole can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Astemizole can be decreased when combined with Cimetidine.Approved, Investigational
CinacalcetThe metabolism of Astemizole can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Astemizole can be decreased when combined with Citalopram.Approved
ClarithromycinThe serum concentration of Astemizole can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Astemizole can be decreased when combined with Clemastine.Approved, Investigational
ClobazamThe metabolism of Astemizole can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Astemizole can be decreased when combined with Clomipramine.Approved, Investigational, Vet Approved
ClotrimazoleThe metabolism of Astemizole can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Astemizole can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Astemizole can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Astemizole can be decreased when combined with Cocaine.Approved, Illicit
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Astemizole.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Astemizole.Approved, Investigational
CrizotinibThe metabolism of Astemizole can be decreased when combined with Crizotinib.Approved
CurcuminThe serum concentration of Astemizole can be increased when it is combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Astemizole can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Astemizole.Approved
DabrafenibThe serum concentration of Astemizole can be decreased when it is combined with Dabrafenib.Approved, Investigational
DarifenacinThe metabolism of Astemizole can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Astemizole can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Astemizole can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Astemizole can be decreased when it is combined with Deferasirox.Approved, Investigational
DelamanidAstemizole may increase the QTc-prolonging activities of Delamanid.Approved, Investigational
DelavirdineDelavirdine may increase the arrhythmogenic activities of Astemizole.Approved
DesipramineThe metabolism of Astemizole can be decreased when combined with Desipramine.Approved, Investigational
DeutetrabenazineAstemizole may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
DextroamphetamineDextroamphetamine may decrease the sedative activities of Astemizole.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Astemizole.Approved, Illicit
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Astemizole.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Astemizole.Approved, Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Astemizole.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Astemizole.Approved, Investigational
DiltiazemThe metabolism of Astemizole can be decreased when combined with Diltiazem.Approved, Investigational
DiphenhydramineThe metabolism of Astemizole can be decreased when combined with Diphenhydramine.Approved, Investigational
DosulepinThe metabolism of Astemizole can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Astemizole.Approved, Investigational
DoxycyclineThe metabolism of Astemizole can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Astemizole can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Astemizole can be decreased when combined with Duloxetine.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Astemizole.Approved
EliglustatThe metabolism of Astemizole can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Astemizole can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Astemizole.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Astemizole.Approved
ErythromycinThe metabolism of Astemizole can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Astemizole.Approved
FluconazoleThe metabolism of Astemizole can be decreased when combined with Fluconazole.Approved, Investigational
FluoxetineThe metabolism of Astemizole can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Astemizole.Approved
FluvoxamineThe metabolism of Astemizole can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Astemizole can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Astemizole can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Astemizole can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Astemizole can be increased when it is combined with Fusidic Acid.Approved, Investigational
GepefrineGepefrine may decrease the sedative activities of Astemizole.Experimental
HaloperidolThe metabolism of Astemizole can be decreased when combined with Haloperidol.Approved
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Astemizole.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Astemizole.Approved
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Astemizole.Approved
IdelalisibThe serum concentration of Astemizole can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Astemizole can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Astemizole can be decreased when combined with Imipramine.Approved
IndinavirThe serum concentration of Astemizole can be increased when it is combined with Indinavir.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Astemizole.Approved
IsavuconazoleThe serum concentration of Astemizole can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Astemizole can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Astemizole can be decreased when combined with Isoniazid.Approved, Investigational
IsradipineThe metabolism of Astemizole can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe serum concentration of Astemizole can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Astemizole can be increased when it is combined with Ivacaftor.Approved
KetoconazoleKetoconazole may increase the QTc-prolonging activities of Astemizole.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Astemizole.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Astemizole.Approved, Investigational
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Astemizole.Approved, Investigational
LopinavirThe serum concentration of Astemizole can be increased when it is combined with Lopinavir.Approved
LorcaserinThe metabolism of Astemizole can be decreased when combined with Lorcaserin.Approved
LorpiprazoleThe serum concentration of Astemizole can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Astemizole.Approved, Investigational
LuliconazoleThe serum concentration of Astemizole can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Astemizole can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Astemizole can be decreased when combined with Lumefantrine.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Astemizole.Illicit, Investigational, Withdrawn
MacimorelinAstemizole may increase the QTc-prolonging activities of Macimorelin.Approved, Investigational
ManidipineThe metabolism of Astemizole can be decreased when combined with Manidipine.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Astemizole.Investigational
MephentermineMephentermine may decrease the sedative activities of Astemizole.Approved
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Astemizole.Experimental
MethadoneThe metabolism of Astemizole can be decreased when combined with Methadone.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Astemizole.Approved, Illicit
MethotrimeprazineThe metabolism of Astemizole can be decreased when combined with Methotrimeprazine.Approved, Investigational
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Astemizole.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Astemizole.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Astemizole.Approved
MetoprololThe metabolism of Astemizole can be decreased when combined with Metoprolol.Approved, Investigational
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Astemizole.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Astemizole.Experimental, Illicit, Investigational
MidostaurinThe metabolism of Astemizole can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Astemizole can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Astemizole can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Astemizole can be decreased when it is combined with Mitotane.Approved
MMDAMMDA may decrease the sedative activities of Astemizole.Experimental, Illicit
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Astemizole.Approved
NefazodoneThe serum concentration of Astemizole can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Astemizole can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Astemizole can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Astemizole can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Astemizole can be decreased when combined with Nicardipine.Approved, Investigational
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Astemizole.Approved, Investigational
NilotinibThe metabolism of Astemizole can be decreased when combined with Nilotinib.Approved, Investigational
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Astemizole.Approved
OlaparibThe metabolism of Astemizole can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Astemizole can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Astemizole can be increased when it is combined with Palbociclib.Approved, Investigational
PanobinostatThe serum concentration of Astemizole can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Astemizole can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Astemizole.Approved
Peginterferon alfa-2bThe serum concentration of Astemizole can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Astemizole can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Astemizole.Approved, Investigational, Vet Approved, Withdrawn
PhenobarbitalThe metabolism of Astemizole can be increased when combined with Phenobarbital.Approved, Investigational
PhenterminePhentermine may decrease the sedative activities of Astemizole.Approved, Illicit
PhenytoinThe metabolism of Astemizole can be increased when combined with Phenytoin.Approved, Vet Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Astemizole.Approved
PitolisantThe serum concentration of Astemizole can be decreased when it is combined with Pitolisant.Approved, Investigational
PosaconazoleThe serum concentration of Astemizole can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Astemizole.Approved
PrimidoneThe metabolism of Astemizole can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Astemizole can be decreased when combined with Promazine.Approved, Vet Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Astemizole.Approved
PseudoephedrinePseudoephedrine may decrease the sedative activities of Astemizole.Approved
QuinidineThe metabolism of Astemizole can be decreased when combined with Quinidine.Approved, Investigational
QuinineThe metabolism of Astemizole can be decreased when combined with Quinine.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Astemizole.Approved, Investigational
RibociclibThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Astemizole.Approved, Investigational
RifabutinThe metabolism of Astemizole can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Astemizole can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Astemizole can be increased when combined with Rifapentine.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Astemizole.Approved, Investigational
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Astemizole.Approved
RitobegronRitobegron may decrease the sedative activities of Astemizole.Investigational
RitonavirThe metabolism of Astemizole can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Astemizole can be decreased when combined with Rolapitant.Approved, Investigational
RopiniroleThe metabolism of Astemizole can be decreased when combined with Ropinirole.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Astemizole.Approved
RucaparibThe metabolism of Astemizole can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe serum concentration of Astemizole can be increased when it is combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Astemizole can be decreased when used in combination with Sarilumab.Approved, Investigational
SertralineThe metabolism of Astemizole can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Astemizole can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Astemizole.Approved
SiltuximabThe serum concentration of Astemizole can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Astemizole can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Astemizole.Approved
St. John's WortThe serum concentration of Astemizole can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Astemizole can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Astemizole can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Astemizole can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Astemizole can be increased when it is combined with Telithromycin.Approved
TerbinafineThe metabolism of Astemizole can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Astemizole.Experimental
ThioridazineThe metabolism of Astemizole can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Astemizole can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Astemizole can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Astemizole can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Astemizole.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Astemizole.Approved, Investigational
TranylcypromineThe metabolism of Astemizole can be decreased when combined with Tranylcypromine.Approved, Investigational
VemurafenibThe serum concentration of Astemizole can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Astemizole can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Astemizole can be decreased when combined with Verapamil.Approved
VincristineThe excretion of Vincristine can be decreased when combined with Astemizole.Approved, Investigational
VoriconazoleThe serum concentration of Astemizole can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Astemizole can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Take on an empty stomach, food decreases absorption by 60%.

References

Synthesis Reference

Godelieve Irma Christine Maria Heylen, Cornelus Gerardus Maria Janssen, Jurzak Mirek, Henricus Petrus Martinus Maria Van Assouw, "Radiolabeled astemizole and method of making." U.S. Patent US07541476, issued June 02, 2009.

US07541476
General References
  1. Wang X, Hockerman GH, Green HW 3rd, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL: Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway. FASEB J. 2006 Jul;20(9):1531-3. Epub 2006 May 24. [PubMed:16723379]
  2. Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ Jr: A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol. 2006 Aug;2(8):415-6. Epub 2006 Jul 2. [PubMed:16816845]
External Links
Human Metabolome Database
HMDB0014775
KEGG Drug
D00234
KEGG Compound
C06832
PubChem Compound
2247
PubChem Substance
46508569
ChemSpider
2160
BindingDB
24226
ChEBI
2896
ChEMBL
CHEMBL296419
Therapeutic Targets Database
DAP000326
PharmGKB
PA448498
IUPHAR
2603
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Astemizole
ATC Codes
R06AX11 — Astemizole
MSDS
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Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral10 mg
SuspensionOral2 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)149.1 °CPhysProp
water solubility432 mg/LNot Available
logP5.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0012 mg/mLALOGPS
logP5.92ALOGPS
logP5.39ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)8.75ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area42.32 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity135.64 m3·mol-1ChemAxon
Polarizability52.08 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.765
Caco-2 permeable+0.5217
P-glycoprotein substrateSubstrate0.8162
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.8995
Renal organic cation transporterInhibitor0.7708
CYP450 2C9 substrateNon-substrate0.8732
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6777
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.5127
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9096
Ames testNon AMES toxic0.6444
CarcinogenicityNon-carcinogens0.9553
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2847 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.9267
hERG inhibition (predictor II)Inhibitor0.8575
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
Phenethylamines / Anisoles / Methoxybenzenes / Phenoxy compounds / Alkyl aryl ethers / Fluorobenzenes / Aralkylamines / N-substituted imidazoles / Aryl fluorides / Piperidines
show 6 more
Substituents
Benzimidazole / Phenethylamine / Anisole / Phenoxy compound / Phenol ether / Methoxybenzene / Alkyl aryl ether / Fluorobenzene / Halobenzene / Aralkylamine
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, benzimidazoles (CHEBI:2896)

Targets

Details
1. Histamine H1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Salata JJ, Jurkiewicz NK, Wallace AA, Stupienski RF 3rd, Guinosso PJ Jr, Lynch JJ Jr: Cardiac electrophysiological actions of the histamine H1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine. Circ Res. 1995 Jan;76(1):110-9. [PubMed:8001268]
  2. Howarth PH, Emanuel MB, Holgate ST: Astemizole, a potent histamine H1-receptor antagonist: effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin weal responses and relationship to serum levels. Br J Clin Pharmacol. 1984 Jul;18(1):1-8. [PubMed:6146346]
  3. Kaliner MA, Check WA: Non-sedating antihistamines. Allergy Proc. 1988 Nov-Dec;9(6):649-63. [PubMed:3147222]
  4. Cavero I, Mestre M, Guillon JM, Heuillet E, Roach AG: Preclinical in vitro cardiac electrophysiology: a method of predicting arrhythmogenic potential of antihistamines in humans? Drug Saf. 1999;21 Suppl 1:19-31; discussion 81-7. [PubMed:10597865]
  5. Llenas J, Cardelus I, Heredia A, de Mora F, Gristwood RW: Cardiotoxicity of histamine and the possible role of histamine in the arrhythmogenesis produced by certain antihistamines. Drug Saf. 1999;21 Suppl 1:33-8; discussion 81-7. [PubMed:10597866]
  6. Richards DM, Brogden RN, Heel RC, Speight TM, Avery GS: Astemizole. A review of its pharmacodynamic properties and therapeutic efficacy. Drugs. 1984 Jul;28(1):38-61. [PubMed:6204835]
  7. Krstenansky PM, Cluxton RJ Jr: Astemizole: a long-acting, nonsedating antihistamine. Drug Intell Clin Pharm. 1987 Dec;21(12):947-53. [PubMed:2892659]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Zhou Z, Vorperian VR, Gong Q, Zhang S, January CT: Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J Cardiovasc Electrophysiol. 1999 Jun;10(6):836-43. [PubMed:10376921]
  2. Chachin M, Katayama Y, Yamada M, Horio Y, Ohmura T, Kitagawa H, Uchida S, Kurachi Y: Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel. Eur J Pharmacol. 1999 Jun 25;374(3):457-60. [PubMed:10422790]
  3. Taglialatela M, Castaldo P, Pannaccione A, Giorgio G, Genovese A, Marone G, Annunziato L: Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity. Clin Exp Allergy. 1999 Jul;29 Suppl 3:182-9. [PubMed:10444235]
  4. Grzelewska-Rzymowska I, Pietrzkowicz M, Gorska M: [The effect of second generation histamine antagonists on the heart]. Pneumonol Alergol Pol. 2001;69(3-4):217-26. [PubMed:11575008]
  5. Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [PubMed:15272206]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphorelay sensor kinase activity
Specific Function
Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:22732247). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (By sim...
Gene Name
KCNH1
Uniprot ID
O95259
Uniprot Name
Potassium voltage-gated channel subfamily H member 1
Molecular Weight
111421.76 Da
References
  1. Garcia-Ferreiro RE, Kerschensteiner D, Major F, Monje F, Stuhmer W, Pardo LA: Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J Gen Physiol. 2004 Oct;124(4):301-17. Epub 2004 Sep 13. [PubMed:15365094]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neu...
Gene Name
MAPT
Uniprot ID
P10636
Uniprot Name
Microtubule-associated protein tau
Molecular Weight
78927.025 Da
References
  1. Rojo LE, Alzate-Morales J, Saavedra IN, Davies P, Maccioni RB: Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease. J Alzheimers Dis. 2010;19(2):573-89. doi: 10.3233/JAD-2010-1262. [PubMed:20110603]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Nicolas JM, Whomsley R, Collart P, Roba J: In vitro inhibition of human liver drug metabolizing enzymes by second generation antihistamines. Chem Biol Interact. 1999 Nov 15;123(1):63-79. [PubMed:10597902]
  2. Matsumoto S, Yamazoe Y: Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine. Br J Clin Pharmacol. 2001 Feb;51(2):133-42. [PubMed:11259984]
  3. Cvetkovic RS, Goa KL: Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802. [PubMed:12662125]
  4. Goto A, Adachi Y, Inaba A, Nakajima H, Kobayashi H, Sakai K: Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity. Biol Pharm Bull. 2004 May;27(5):684-90. [PubMed:15133245]
  5. Goto A, Ueda K, Inaba A, Nakajima H, Kobayashi H, Sakai K: Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants. Biol Pharm Bull. 2005 Feb;28(2):328-34. [PubMed:15684493]
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  7. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  8. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
Molecular Weight
57610.165 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
  2. Ishikawa M, Fujita R, Takayanagi M, Takayanagi Y, Sasaki K: Reversal of acquired resistance to doxorubicin in K562 human leukemia cells by astemizole. Biol Pharm Bull. 2000 Jan;23(1):112-5. [PubMed:10706423]

Drug created on June 13, 2005 07:24 / Updated on June 02, 2018 06:38