DEXCHLORPHENIRAMINE

US Approved OTC

First approved in 1958

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H19ClN2
Molecular Weight	274.788
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CC[C@@H](C1=CC=C(Cl)C=C1)C2=CC=CC=N2

InChI

InChIKey=SOYKEARSMXGVTM-HNNXBMFYSA-N

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/t15-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.medsafe.govt.nz/profs/Datasheet/p/Polaraminetabreptabsyrup.pdf

Dexchlorpheniramine, the d-isomer of the racemic compound chlorpheniramine, is two times more active than chlorpheniramine. Dexchlorpheniramine does not prevent the release of histamine, but rather, competes with free histamine for binding at the H1-receptor sites, and competitively antagonizes the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Blockade of H1-receptors also suppresses the formation of oedema, flare, and pruritus that result from histaminic activity. Since dexchlorpheniramine binds to central and peripheral H1-receptors, sedative effects are likely to occur. H1-antagonists are structurally similar to anticholinergic agents and therefore possess the potential to exhibit anticholinergic properties of varying degrees. They also have antipruritic effects. Dexchlorpheniramine has high antihistaminic activity, moderate anticholinergic effects and minimal sedative effects. The drug does not possess antiemetic properties.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: http://www.auburn.edu/~deruija/hist_antihis.pdf \| http://www.medsafe.govt.nz/profs/Datasheet/p/Polaraminetabreptabsyrup.pdf	Antagonist 2778
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: http://www.auburn.edu/~deruija/hist_antihis.pdf	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergy 44 Sources: http://www.medsafe.govt.nz/profs/Datasheet/p/Polaraminetabreptabsyrup.pdf	Primary		Approved 8429	POLARAMINE Approved Use POLARAMINE is indicated for symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, mild uncomplicated allergic skin manifestations of urticaria and angioedema. Polaramine may relieve itching due to skin conditions such as allergic eczema, pruritus ani, pruritus vulvae, atopic dermatitis, contact dermatitis, insect bites, dermographism and drug reactions, including serum sickness. Launch Date 1981

C_max

Value	Dose	Co-administered	Analyte	Population
2.5 ng/mL EXPERIMENT http://en.cnki.com.cn/Article_en/CJFDTotal-BSDZ200803014.htm	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	DEXCHLORPHENIRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
67.58 ng × h/mL EXPERIMENT http://en.cnki.com.cn/Article_en/CJFDTotal-BSDZ200803014.htm	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	DEXCHLORPHENIRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
19.66 h EXPERIMENT http://en.cnki.com.cn/Article_en/CJFDTotal-BSDZ200803014.htm	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	DEXCHLORPHENIRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
28% EXPERIMENT http://en.cnki.com.cn/Article_en/CJFDTotal-BSDZ200803014.htm	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	DEXCHLORPHENIRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
6 mg 2 times / day steady, oral Recommended Dose: 6 mg, 2 times / day Route: oral Route: steady Dose: 6 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16390354/	healthy, 22 - 45 years n = 4 Health Status: healthy Age Group: 22 - 45 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/16390354/	Other AEs: Sedation... Other AEs: Sedation (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16390354/
6 mg single, oral Recommended Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2972549/	healthy, mean 27 years n = 12 Health Status: healthy Age Group: mean 27 years Sex: F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/2972549/	Other AEs: Depressive symptom... Other AEs: Depressive symptom (10 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/2972549/

AEs

AE	Significance	Dose	Population
Sedation	4 patients	6 mg 2 times / day steady, oral Recommended Dose: 6 mg, 2 times / day Route: oral Route: steady Dose: 6 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16390354/	healthy, 22 - 45 years n = 4 Health Status: healthy Age Group: 22 - 45 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/16390354/
Depressive symptom	10 patients	6 mg single, oral Recommended Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2972549/	healthy, mean 27 years n = 12 Health Status: healthy Age Group: mean 27 years Sex: F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/2972549/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4464	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4464
ZINC	ZINC000000113404	http://zinc15.docking.org/substances/ZINC000000113404
eMolecules	8791345	https://www.emolecules.com/cgi-bin/more?vid=8791345

PubMed

Title	Date	PubMed
Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene.	1994 Sep 1	7925364
Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.	2001 Mar 1	11230474
Phase I trial and pharmacological study of a 3-hour paclitaxel infusion in children with refractory solid tumours: a SFOP study.	2001 Mar 2	11237379
Determination of active ingredients in cough-cold preparations by micellar liquid chromatography.	2001 May 30	18968285
Sequential atomic force microscopy imaging of a spontaneous nanoencapsulation process.	2002 Aug 21	12176266
The effects of a sedative antihistamine, d-chlorpheniramine, on visuomotor spatial discrimination and regional brain activity as measured by positron emission tomography (PET).	2002 Dec	12457377
Possible involvement of tachykinin NK(1) and NMDA receptors in histamine-induced hyperalgesia in mice.	2002 Jan 2	11755162
Rodent antinociception following acute treatment with different histamine receptor agonists and antagonists.	2002 Jun	12175473
Development of a validated capillary electrophoresis method for enantiomeric purity testing of dexchlorpheniramine maleate.	2002 Jun 7	12134827
Uniformly sized molecularly imprinted polymer for d-chlorpheniramine. Evaluation of retention and molecular recognition properties in an aqueous mobile phase.	2002 Mar 1	12831185
The involvement of nervous and some inflammatory response mechanisms in the acute snuff-induced gingival hyperaemia in humans.	2002 Sep	12423300
Two cases of cross-sensitivity in subjects allergic to paraphenylenediamine following ingestion of Polaronil.	2003	12771491
Histamine inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in an intercellular adhesion molecule-1- and B7.1-dependent manner.	2003 Feb	12538815
Self-assembly of drug-polymer complexes: a spontaneous nanoencapsulation process monitored by atomic force microscopy.	2003 Jan	12486684
Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors.	2003 Jan	12479971
Aseptic meningitis associated with intravenous administration of dexchlorpheniramine.	2003 May	12910046
[Roles of histamine receptors in pain perception: a study using receptors gene knockout mice].	2003 Nov	14569158
A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo.	2004 Feb	14987305
[Herpes gestationis].	2004 Jan-Feb	15636736
Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species.	2004 May	15093820
Retentivity and enantioselectivity of uniformly sized molecularly imprinted polymers for d-chlorpheniramine and -brompheniramine in hydro-organic mobile phases.	2004 May 5	15093155
An unusual adverse drug reaction?	2005 Jul-Aug	16045865
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Severe anaphylactic reaction after intracameral antibiotic administration during cataract surgery.	2005 Mar	15811754
Derivative ultraviolet spectrophotometric determination of dexchlorpheniramine maleate in tablets in presence of coloring agents.	2005 Nov-Dec	16226263
Histamine H1 antagonists block M-currents in dissociated rat cortical neurons.	2005 Sep 28	16125149
Interventions for pityriasis rosea.	2007 Apr 18	17443568
Modification of formalin-induced nociception by different histamine receptor agonists and antagonists.	2007 Jan 15	16631358
Anaphylactic reaction to ranitidine and dexchlorpheniramine.	2007 Mar-Apr	17337410
Role of histaminergic neurons in hypnotic modulation of brain processing of visceral perception.	2007 Oct	17883434
Anaphylaxis to oral iron salts. desensitization protocol for tolerance induction.	2008	18714540
Analysis of disease-dependent sedative profiles of H(1)-antihistamines by large-scale surveillance using the visual analog scale.	2008 Apr	18597008
Histamine H1-receptor blockade in humans affects psychomotor performance but not memory.	2008 Aug	18208925
Anaphylaxis induced by Anisakis.	2008 Jan-Feb	18261432
Cocaine-like neurochemical effects of antihistaminic medications.	2008 Jul	18363822
Progress in allergy signal research on mast cells: up-regulation of histamine signal-related gene expression in allergy model rats.	2008 Mar	18360087
Effects of a sedative antihistamine, D-chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving.	2008 Mar	18181241
'Renal hypersensitivity' to inulin and IgA nephropathy.	2008 Oct	18535847
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).	2008 Sep	18566547
Fexofenadine hydrochloride in the treatment of allergic disease: a review.	2008 Sep 19	21436982
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines.	2009 Aug 31	21437146
Histamine H1 receptor blockade predominantly impairs sensory processes in human sensorimotor performance.	2009 May	19220286
[A case of IgG4-positive multi-organ lymphoproliferative syndrome associated with Kimura disease].	2010 Jul	20684218
Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study.	2010 Jul	19924675
Network-based relating pharmacological and genomic spaces for drug target identification.	2010 Jul 26	20668676
Urticaria due to aloe vera: a new sensitizer?	2010 Nov	21055672

Patents

Sample Use Guides

In Vivo Use Guide

Polaramine (dexchlorpheniramine maleate) Tablets Adults and children over 12 years: One tablet every 6 hours Polaramine Syrup Adults and children over 12 years: 5 mL every 6 hours Children 6 – 12 years: 2 – 4 mL every 6 - 8 hours Children 4 - 6 years: 1.75 – 2 mL every 6 - 8 hours Children 2 – 4 years: 1.25 – 1.75 mL every 6 - 8 hours

Route of Administration: Oral

In Vitro Use Guide

dexchlorpheniramine (< 0.62 uM) altered the growth kinetics of RPMI 8866 (B-cell line)

Name

Type

Language

DEXCHLORPHENIRAMINE

Official Name

English

CHLORPHENIRAMINE D-FORM [MI]

Common Name

English

DAPRITON

Brand Name

English

CHLORPHENIRAMINE, (S)-

Common Name

English

DEXCHLORPHENIRAMINE [VANDF]

Common Name

English

CHLORPHENAMINE, (S)-

Common Name

English

dexchlorpheniramine [INN]

Common Name

English

CHLORPHENIRAMINE, D-

Common Name

English

2-PYRIDINEPROPANAMINE, .GAMMA.-(4-CHLOROPHENYL)-N,N-DIMETHYL-, (.GAMMA.S)-

Systematic Name

English

DEXCHLORPHENIRAMINE [HSDB]

Common Name

English

CHLORPHENIRAMINE D-FORM

Common Name

English

Dexchlorpheniramine [WHO-DD]

Common Name

English

Classification Tree Code System Code

LIVERTOX

289