astemizole 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antihistaminics 249 68844-77-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • R 43 512
  • astemizole
  • astemisan
  • hismanal
  • histazol
Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects.
  • Molecular weight: 458.58
  • Formula: C28H31FN4O
  • CLOGP: 5.84
  • LIPINSKI: 1
  • HAC: 5
  • HDO: 1
  • TPSA: 42.32
  • ALOGS: -5.58
  • ROTB: 8

Drug dosage:

DoseUnitRoute
10 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.36 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 10 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.123 High 0.83
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.656 High 0.83
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 6.776 10^-6 cm/s High 0.83
dh-clint Dog hepatocyte intrinsic clearance 35.318 uL/min/10^6 cells High 0.83
dppb Dog plasma protein binding (% unbound) 2.470 % High 0.83
fcs-ppb Fetal calf serum protein binding (% unbound) 9.360 % High 0.83
herg hERG pIC50 6.486 pIC50 High 0.83
hh-clint Human hepatocyte intrinsic clearance 13.996 uL/min/10^6 cells High 0.83
hlm-clint Human liver microsomal intrinsic clearance 214.289 uL/min/mg protein High 0.83
hppb Human plasma protein binding (% unbound) 2.730 % High 0.83
kinase-safety-class ACVR2B,AKT2,AKT3,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,MAPK10,MAPK7,MET,NTRK2,PDK2,PDK4,PRKDC,SIK3,TTK 24
kinase-selectivity-class AXL,DYRK1B,GRK2 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.805 High 0.83
mh-clint Mouse hepatocyte intrinsic clearance 113.763 High 0.83
mppb Mouse plasma protein binding (% unbound) 2.370 High 0.83
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 7.727 High 0.83
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 6.400 % High 0.83
rh-clint Rat hepatocyte intrinsic clearance 115.080 uL/min/10^6 cells High 0.83
rh-fuinc Rat hepatocyte fraction unbound in incubation 6.710 % High 0.83
rppb Rat plasma protein binding (% unbound) 2.690 % High 0.83
solubility-dd Solubility at pH 7.4 in DMSO 2.805 uM High 0.83

Approvals:

DateAgencyCompanyOrphan
Dec. 31, 1988 FDA

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC R06AX11 RESPIRATORY SYSTEM
ANTIHISTAMINES FOR SYSTEMIC USE
ANTIHISTAMINES FOR SYSTEMIC USE
Other antihistamines for systemic use
CHEBI has role CHEBI:37955 H<small><sub>1</sub></small>-receptor antagonist
CHEBI has role CHEBI:50857 anti-allergic agent
CHEBI has role CHEBI:149553 anticoronaviral agent
MeSH PA D006633 Histamine Antagonists
MeSH PA D006634 Histamine H1 Antagonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018926 Anti-Allergic Agents
MeSH PA D039563 Histamine H1 Antagonists, Non-Sedating

Related Drugs by ATC class:

R06AX Other antihistamines for systemic use 26 drugs
acrivastineantazolineazatadineazelastinebamipinebilastinecyproheptadinedeptropinedesloratadineebastineepinastinefexofenadine show all 26 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Allergic rhinitis indication 61582004
Sneezing indication 76067001
Chronic idiopathic urticaria indication 302162004
Allergic conjunctivitis indication 473460002 DOID:11204
Urticaria off-label use 126485001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.47 Basic
pKa2 5.81 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Histamine H1 receptor GPCR ANTAGONIST A2 8.58 WOMBAT-PK SCIENTIFIC LITERATURE
Beta-1 adrenergic receptor GPCR Ki 5.00 DRUG MATRIX
Mu-type opioid receptor GPCR Ki 6.22 DRUG MATRIX
D(1A) dopamine receptor GPCR Ki 5.70 DRUG MATRIX
D(2) dopamine receptor GPCR Ki 5.82 DRUG MATRIX
Alpha-2A adrenergic receptor GPCR Ki 5.74 DRUG MATRIX
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 6.03 DRUG MATRIX
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 9.05 WOMBAT-PK
Cytochrome P450 3A4 Enzyme IC50 5.48 WOMBAT-PK
Multidrug resistance protein 1 Transporter IC50 6.05 WOMBAT-PK
Sodium-dependent serotonin transporter Transporter Ki 6.16 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 5.87 DRUG MATRIX
5-hydroxytryptamine receptor 1A GPCR Ki 6.36 DRUG MATRIX
5-hydroxytryptamine receptor 2A GPCR Ki 8.25 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 8.13 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 7.03 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 5.82 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 5.76 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.83 DRUG MATRIX
Histamine H2 receptor GPCR Ki 5.78 DRUG MATRIX
Histamine H4 receptor GPCR Ki 5.10 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 6.59 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 6.30 DRUG MATRIX
Muscarinic acetylcholine receptor M3 GPCR Ki 6.75 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 6.59 DRUG MATRIX
Muscarinic acetylcholine receptor M5 GPCR Ki 6.30 DRUG MATRIX
Beta-3 adrenergic receptor GPCR Ki 5.22 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 6.55 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 6.10 DRUG MATRIX
Adenosine receptor A3 GPCR Ki 4.78 DRUG MATRIX
D(4) dopamine receptor GPCR Ki 5.67 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 8.00 DRUG MATRIX
5-hydroxytryptamine receptor 3A Ion channel Ki 7.02 DRUG MATRIX
Kappa-type opioid receptor GPCR Ki 5.58 DRUG MATRIX
ATP-binding cassette sub-family G member 2 Transporter WOMBAT-PK
Glycine receptor subunit alpha-1 Ion channel EC50 5.38 CHEMBL
Calmodulin Cytosolic other IC50 6 WOMBAT-PK
Delta-type opioid receptor GPCR Ki 5.34 DRUG MATRIX
Somatostatin receptor type 5 GPCR Ki 5.39 CHEMBL
Epidermal growth factor receptor Kinase IC50 5.22 DRUG MATRIX
Substance-P receptor GPCR Ki 5.07 DRUG MATRIX
Tyrosine-protein kinase Lck Kinase IC50 4.70 DRUG MATRIX
Tyrosine-protein kinase Fyn Kinase IC50 5.55 DRUG MATRIX
Receptor tyrosine-protein kinase erbB-2 Kinase IC50 4.88 DRUG MATRIX
Substance-K receptor GPCR Ki 6.00 DRUG MATRIX
Potassium voltage-gated channel subfamily H member 1 Ion channel BLOCKER IC50 6.70 IUPHAR
Melanocortin receptor 4 GPCR Ki 4.87 DRUG MATRIX
Melanocortin receptor 5 GPCR Ki 5.67 DRUG MATRIX
Melanocortin receptor 3 GPCR Ki 4.87 DRUG MATRIX
Sodium/nucleoside cotransporter 1 Transporter Ki 5.31 DRUG MATRIX
Multidrug and toxin extrusion protein 1 Transporter IC50 4.58 CHEMBL
Polycomb protein EED Nuclear other IC50 4.03 CHEMBL
HLA class I histocompatibility antigen, A-3 alpha chain Surface antigen Kd 5.60 CHEMBL
Transmembrane protein 97 Enzyme Ki 7.02 CHEMBL
Nuclear receptor subfamily 4 group A member 2 Nuclear other Kd 4 CHEMBL
Alpha-1B adrenergic receptor GPCR Ki 7.02 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 6.20 DRUG MATRIX
Membrane-associated progesterone receptor component 1 Membrane receptor Ki 6.73 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 7.62 CHEMBL
Protein farnesyltransferase Enzyme IC50 8.70 CHEMBL
5-hydroxytryptamine receptor 1A GPCR IC50 6.12 CHEMBL

External reference:

IDSource
4019379 VUID
N0000147536 NUI
D00234 KEGG_DRUG
202818 RXNORM
C0085170 UMLSCUI
CHEBI:2896 CHEBI
XB7 PDB_CHEM_ID
CHEMBL296419 ChEMBL_ID
CHEMBL61301 ChEMBL_ID
D016589 MESH_DESCRIPTOR_UI
DB00637 DRUGBANK_ID
2603 IUPHAR_LIGAND_ID
4755 INN_ID
7HU6337315 UNII
2247 PUBCHEM_CID
4224 MMSL
768 MMSL
d00794 MMSL
4019379 VANDF
003413 NDDF
387333002 SNOMEDCT_US
59456005 SNOMEDCT_US
7HU6337315 INXIGHT DRUGS

Pharmaceutical products:

None