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Identification
NameChlorphenamine
Accession NumberDB01114  (APRD00001)
Typesmall molecule
Groupsapproved
Description

A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1-(p-chlorophenyl)-1-(2-pyridyl)-3-dimethylaminopropaneNot AvailableNot Available
ChlorophenylpyridamineNot AvailableNot Available
ChlorphenaminGermanNot Available
ChlorpheniramineNot AvailableUSAN
ClorfeniraminaNot AvailableNot Available
γ-(4-chlorophenyl)-γ-(2-pyridyl)propyldimethylamineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Chlorpheniramine maleate
Thumb Not applicable DBSALT000987
Brand names
NameCompany
Aller-ChlorRugby
Chlo-AmineNot Available
Chlor-TrimetonSchering-Plough
Chlor-TripolonNot Available
HaynonNot Available
PiritonGlaxoSmithKline
Brand mixtures
Brand NameIngredients
Alka Seltzer Plus Cold Medicine EvtAcetylsalicylic Acid + Chlorpheniramine Maleate + Phenylpropanolamine Bitartrate
Anakit Insect Sting Treatment KitChlorpheniramine Maleate + Epinephrine
Bronchodex DChlorpheniramine Maleate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride
Children's Tylenol Cold Chewable TabletsAcetaminophen + Chlorpheniramine Maleate + Pseudoephedrine Hydrochloride
Children's Tylenol Cold LiquidAcetaminophen + Chlorpheniramine Maleate + Pseudoephedrine Hydrochloride
Children's Tylenol Cold Liquid with DMAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Chlor Tripolon DecongestChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Cold Decongestant Long ActingChlorpheniramine Maleate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride
Coltalin TabletAcetaminophen + Chlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Contac Cold CapsulesChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Contac Cold Extra Strength CapsulesChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Contac Cough Cold and Flu CapletsAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Phenylpropanolamine Hydrochloride
Contact CChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
CoricidinAcetylsalicylic Acid + Chlorpheniramine Maleate
Coricidin DAcetylsalicylic Acid + Chlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Corsym SuspensionChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Counteract Sinus and AllergyAcetaminophen + Chlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Dristan CapsulesAcetylsalicylic Acid + Caffeine + Chlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Entre-SDextromethorphan + Pseudoephedrine + Chlorphenamine
Extra Strength Allergy Plus Sinus ReliefAcetaminophen + Chlorpheniramine Maleate + Pseudoephedrine Hydrochloride
Extra Strength Allergy Sinus MedicationAcetaminophen + Chlorpheniramine Maleate + Pseudoephedrine Hydrochloride
Extra Strength Contac CChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Extra Strength Nighttime Cold Relief-CapletAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Extra Strength Tylenol Cold and Flu PowderAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Extra Strength Tylenol Cold Nighttime CapletAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Extra Strength Tylenol Sinus NighttimeAcetaminophen + Chlorpheniramine Maleate + Pseudoephedrine Hydrochloride
Grippalin & CAcetaminophen + Chlorpheniramine Maleate + Vitamin C
Neocitran TotalAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Omni-TussChlorpheniramine + Codeine + Ephedrine As Resin Complex + Guaiacol Carbonate + Phenyltoloxamine
Once-a-Day Benylin ColdChlorpheniramine Maleate + Pseudoephedrine Hydrochloride
Ornade DMChlorpheniramine Maleate + Dextromethorphan Hydrobromide + Phenylpropanolamine Hydrochloride
Ornade Expectorant Cough FormulaChlorpheniramine Maleate + Guaifenesin + Phenylpropanolamine Hydrochloride
Ornade LiquidChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
PendamineChlorpheniramine Maleate + Dexamethasone + Dihydrostreptomycin Sulfate + Penicillin G Procaine
Pentuss SRSChlorpheniramine Maleate + Codeine
Regular Strength Tylenol Cold and Flu PowderAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Regular Strength Tylenol Cold Nighttime CapletAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
RhinofebralChlorpheniramine Maleate + Acetaminophen + Vitamin C
Sine-Off AllergyAcetaminophen + Chlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Theraflu Flu Cold and Cough MedicineAcetaminophen + Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
Tri-Anamine Cold SyrupChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Triaminic Cold and Allergy SyrupChlorpheniramine Maleate + Phenylpropanolamine Hydrochloride
Triaminic DM Expectorant SyrupChlorpheniramine Maleate + Dextromethorphan Hydrobromide + Guaifenesin + Pseudoephedrine Hydrochloride
Triaminic Expectorant SyrupChlorpheniramine Maleate + Guaifenesin + Pseudoephedrine Hydrochloride
Triaminicol DM SyrupChlorpheniramine Maleate + Dextromethorphan Hydrobromide + Pseudoephedrine Hydrochloride
TussiCapsHydrocodone + Chlorphenamine
VituzHydrocodone + Chlorphenamine
ZUTRIPROPseudoephedrine + Hydrocodone + Chlorphenamine
Categories
CAS number132-22-9
WeightAverage: 274.788
Monoisotopic: 274.123676325
Chemical FormulaC16H19ClN2
InChI KeySOYKEARSMXGVTM-UHFFFAOYSA-N
InChI
InChI=1S/C16H19ClN2/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13/h3-9,11,15H,10,12H2,1-2H3
IUPAC Name
[3-(4-chlorophenyl)-3-(pyridin-2-yl)propyl]dimethylamine
SMILES
CN(C)CCC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyridines and Derivatives
SubclassPheniramines
Direct parentPheniramines
Alternative parentsPhenylpropylamines; Chlorobenzenes; Aryl Chlorides; Tertiary Amines; Polyamines; Organochlorides
Substituentsphenylpropylamine; chlorobenzene; aryl chloride; benzene; aryl halide; tertiary amine; polyamine; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the pheniramines. These are compounds containing a pheniramine moiety, which is structurally characterized by the presence of a 2-benzylpyridine linked to an dimethyl(propyl)amine to form a dimethyl[3-phenyl-3-(pyridin-2-yl)propyl]amine skeleton.
Pharmacology
IndicationFor the treatment of rhinitis, urticaria, allergy, common cold, asthma and hay fever.
PharmacodynamicsIn allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.
Mechanism of actionChlorpheniramine 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.
AbsorptionWell absorbed in the gastrointestinal tract.
Volume of distributionNot Available
Protein binding72%
Metabolism

Primarily hepatic via Cytochrome P450 (CYP450) enzymes.

Route of eliminationNot Available
Half life21-27 hours
ClearanceNot Available
ToxicityOral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9754
Blood Brain Barrier + 0.962
Caco-2 permeable + 0.8749
P-glycoprotein substrate Substrate 0.6136
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.9376
Renal organic cation transporter Inhibitor 0.7916
CYP450 2C9 substrate Non-substrate 0.8026
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.6472
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9096
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9023
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7501
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9183
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 3.3361 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8702
hERG inhibition (predictor II) Inhibitor 0.7145
Pharmacoeconomics
Manufacturers
  • Sandoz inc
  • Glaxosmithkline
  • Bel mar laboratories inc
  • Elkins sinn div ah robins co inc
  • Watson laboratories inc
  • Schering plough healthcare products inc
  • Pharmaceutical assoc inc div beach products
  • Schering corp sub schering plough corp
  • Avanthi inc
  • Alza corp
  • Bayer pharmaceuticals corp
  • Anabolic inc
  • Bell pharmacal corp
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kv pharmaceutical co
  • Lederle laboratories div american cyanamid co
  • Mutual pharmaceutical co inc
  • Newtron pharmaceuticals inc
  • Panray corp sub ormont drug and chemical co inc
  • Pharmavite pharmaceuticals
  • Pharmeral inc
  • Pioneer pharmaceuticals inc
  • Purepac pharmaceutical co
  • Private formulations inc
  • Roxane laboratories inc
  • Vitarine pharmaceuticals inc
  • West ward pharmaceutical corp
  • Halsey drug co inc
  • Lannett co inc
  • Wockhardt eu operations (swiss) ag
  • Pliva inc
Packagers
Dosage forms
FormRouteStrength
SyrupOral
TabletOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Ahist 12 mg tablet1.1USDtablet
Myci chlor-tan 8 mg caplet0.75USDcaplet
Chlorpheniramine powder0.67USDg
Chlor-trimeton allergy0.31USDeach
Chlor-trimeton 8 mg repetab0.24USDtablet
Aller-chlor 4 mg tablet0.06USDtablet
Pediacare allergy solution0.05USDml
Allergy 4 mg tablet0.04USDtablet
Chlorpheniramine 4 mg tablet0.02USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
boiling point142 °CNot Available
water solubility5500 mg/L (at 37 °C)BEILSTEIN
logP3.38HANSCH,C ET AL. (1995)
pKa9.13 (at 25 °C)PERRIN,DD (1965)
Predicted Properties
PropertyValueSource
water solubility5.19e-02 g/lALOGPS
logP3.74ALOGPS
logP3.58ChemAxon
logS-3.7ALOGPS
pKa (strongest basic)9.47ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area16.13ChemAxon
rotatable bond count5ChemAxon
refractivity80.85ChemAxon
polarizability30.82ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
References
Synthesis Reference

Anil M. Salpekar, John Johnson, “Acetaminophen compositions containing low doses of chlorpheniramine maleate, method for preparing same and tablets formed therefrom.” U.S. Patent US4631284, issued April, 1975.

US4631284
General Reference
External Links
ResourceLink
KEGG DrugD07398
KEGG CompoundC06905
PubChem Compound2725
PubChem Substance46508253
ChemSpider2624
BindingDB35938
ChEBI52010
ChEMBLCHEMBL505
Therapeutic Targets DatabaseDAP000336
PharmGKBPA448960
IUPHAR1213
Guide to Pharmacology1213
Drug Product Database2265559
RxListhttp://www.rxlist.com/cgi/generic/chlorpheniramine.htm
Drugs.comhttp://www.drugs.com/cdi/chlorpheniramine.html
WikipediaChlorpheniramine
ATC CodesR06AB02R06AB04
AHFS Codes
  • 04:04.20
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.8 KB)
Interactions
Drug Interactions
Drug
DonepezilPossible antagonism of action
EthotoinThe antihistamine increases the effect of hydantoin
FosphenytoinThe antihistamine increases the effect of hydantoin
GalantaminePossible antagonism of action
MephenytoinThe antihistamine increases the effect of hydantoin
PhenytoinThe antihistamine increases the effect of hydantoin
RivastigminePossible antagonism of action
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Chlorpheniramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TelithromycinTelithromycin may reduce clearance of Chlorpheniramine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Chlorpheniramine if Telithromycin is initiated, discontinued or dose changed.
TrimethobenzamideTrimethobenzamide and Chlorpheniramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineTriprolidine and Chlorpheniramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Chlorpheniramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of chlorpheniramine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of chlorpheniramine if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Take with food.

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Tagawa M, Kano M, Okamura N, Higuchi M, Matsuda M, Mizuki Y, Arai H, Iwata R, Fujii T, Komemushi S, Ido T, Itoh M, Sasaki H, Watanabe T, Yanai K: Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine. Br J Clin Pharmacol. 2001 Nov;52(5):501-9. Pubmed
  3. 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
  4. Hasenohrl RU, Kuhlen A, Frisch C, Galosi R, Brandao ML, Huston JP: Comparison of intra-accumbens injection of histamine with histamine H1-receptor antagonist chlorpheniramine in effects on reinforcement and memory parameters. Behav Brain Res. 2001 Oct 15;124(2):203-11. Pubmed
  5. Yasuda SU, Wellstein A, Likhari P, Barbey JT, Woosley RL: Chlorpheniramine plasma concentration and histamine H1-receptor occupancy. Clin Pharmacol Ther. 1995 Aug;58(2):210-20. Pubmed
  6. Nicholson AN, Pascoe PA, Turner C, Ganellin CR, Greengrass PM, Casy AF, Mercer AD: Sedation and histamine H1-receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene. Br J Pharmacol. 1991 Sep;104(1):270-6. Pubmed

2. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

References:

  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

3. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

References:

  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

4. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

References:

  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

Enzymes

1. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J: In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos. 1998 Jun;26(6):536-9. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

Transporters

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. Pubmed

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 11, 2014 17:29