Identification

Name
Chloropyramine
Accession Number
DB08800  (DB07523)
Type
Small Molecule
Groups
Approved
Description

Chloropyramine is a first generation antihistamine drug approved in some Eastern European countries for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. Related indications for clinical use include Quincke's edema, allergic reactions to insect bites, food and drug allergies, and anaphylactic shock.

Structure
Thumb
Synonyms
  • Chloropyramine
  • Chlorpyramine
  • Halopyramine
Product Ingredients
IngredientUNIICASInChI Key
Chloropyramine hydrochlorideFWA92Z14NN6170-42-9VEYWWAGBHABATA-UHFFFAOYSA-N
International/Other Brands
Avapena / Suprastin / Synopen
Categories
UNII
2K3L8O9SOV
CAS number
59-32-5
Weight
Average: 289.803
Monoisotopic: 289.134575362
Chemical Formula
C16H20ClN3
InChI Key
ICKFFNBDFNZJSX-UHFFFAOYSA-N
InChI
InChI=1S/C16H20ClN3/c1-19(2)11-12-20(16-5-3-4-10-18-16)13-14-6-8-15(17)9-7-14/h3-10H,11-13H2,1-2H3
IUPAC Name
N-[(4-chlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]pyridin-2-amine
SMILES
CN(C)CCN(CC1=CC=C(Cl)C=C1)C1=CC=CC=N1

Pharmacology

Indication

For the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions.

Pharmacodynamics

Chloropyramine is known as a competitive reversible H1-receptor antagonist (also known as an H1 inverse agonist), meaning that it exerts its pharmacological action by competing with histamine for the H1 subtype histamine receptor. By blocking the effects of histamine, the drug inhibits the vasodilation, increased vascular permeability, and tissue edema associated with histamine release in the tissue. In addition, chloropyramine has some anticholinergic properties. Chloropyramine's anticholinergic properties and the fact that it can pass through the blood-brain barrier are linked to its clinical side effects: drowsiness, weakness, vertigo, fatigue, dryness in the mouth, constipation, and rarely - visual disturbances and increase of intraocular pressure.

Mechanism of action

Chloropyramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Oral (LD50): Acute: 142 mg/kg [Rat]. 135 mg/kg [Mouse]. DUST (LC50): Acute: 209 mg/m 2 hours [Rat].

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Chloropyramine 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 Chloropyramine.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Chloropyramine.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Chloropyramine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Chloropyramine.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Chloropyramine.Approved, Illicit, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Chloropyramine.Approved, Illicit
Benzylpenicilloyl PolylysineChloropyramine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Chloropyramine.Approved, Investigational
ChlorphentermineChlorphentermine may decrease the sedative activities of Chloropyramine.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Chloropyramine.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Chloropyramine.Approved, Illicit
GepefrineGepefrine may decrease the sedative activities of Chloropyramine.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Chloropyramine.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Chloropyramine.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Chloropyramine.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Chloropyramine.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Chloropyramine.Investigational
MephentermineMephentermine may decrease the sedative activities of Chloropyramine.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Chloropyramine.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Chloropyramine.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Chloropyramine.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Chloropyramine.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Chloropyramine.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Chloropyramine.Approved
RitobegronRitobegron may decrease the sedative activities of Chloropyramine.Investigational
Food Interactions
Not Available

References

Synthesis Reference
US2607778
General References
Not Available
External Links
Human Metabolome Database
HMDB0015690
KEGG Drug
D07195
PubChem Compound
25295
PubChem Substance
99445270
ChemSpider
23628
ChEBI
94767
ChEMBL
CHEMBL1194287
PharmGKB
PA165958419
HET
C4C
Wikipedia
Chloropyramine
ATC Codes
D04AA09 — ChloropyramineR06AC03 — ChloropyramineR06AC53 — Chloropyramine, combinations
MSDS
Download (49.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)154.5 °C at 2.00E-01 mm HgPhysProp
water solubilityInsolubleMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.441 mg/mLALOGPS
logP3.79ALOGPS
logP3.81ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area19.37 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity86.08 m3·mol-1ChemAxon
Polarizability32.25 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.941
Blood Brain Barrier+0.9171
Caco-2 permeable+0.7061
P-glycoprotein substrateSubstrate0.783
P-glycoprotein inhibitor INon-inhibitor0.9316
P-glycoprotein inhibitor IINon-inhibitor0.927
Renal organic cation transporterInhibitor0.741
CYP450 2C9 substrateNon-substrate0.8112
CYP450 2D6 substrateNon-substrate0.734
CYP450 3A4 substrateSubstrate0.5631
CYP450 1A2 substrateInhibitor0.8437
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.9686
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6062
Ames testNon AMES toxic0.9301
CarcinogenicityNon-carcinogens0.8833
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5294 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6398
hERG inhibition (predictor II)Inhibitor0.8005
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 2-benzylaminopyridines. These are aromatic compounds containing pyridine ring substituted at the 2-position by a benzylamine group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylamines
Direct Parent
2-benzylaminopyridines
Alternative Parents
Dialkylarylamines / Chlorobenzenes / Aminopyridines and derivatives / Imidolactams / Aryl chlorides / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides
show 1 more
Substituents
2-benzylaminopyridine / Dialkylarylamine / Aminopyridine / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Imidolactam / Pyridine / Heteroaromatic compound
show 12 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

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. Kurenova EV, Hunt DL, He D, Magis AT, Ostrov DA, Cance WG: Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo. J Med Chem. 2009 Aug 13;52(15):4716-24. doi: 10.1021/jm900159g. [PubMed:19610651]

Drug created on October 14, 2010 14:21 / Updated on June 02, 2018 09:32