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 316 Target ID: CHEMBL231 Sources: http://www.auburn.edu/~deruija/hist_antihis.pdf \| http://www.medsafe.govt.nz/profs/Datasheet/p/Polaraminetabreptabsyrup.pdf	Antagonist 2849
Muscarinic acetylcholine receptor 162 Target ID: CHEMBL2094109 Sources: http://www.auburn.edu/~deruija/hist_antihis.pdf	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergy 44 Sources: http://www.medsafe.govt.nz/profs/Datasheet/p/Polaraminetabreptabsyrup.pdf	Primary		Approved 8583	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 Health Status: healthy Age Group: 22 - 45 years Sex: M+F 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 Health Status: healthy Age Group: mean 27 years Sex: F 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 Health Status: healthy Age Group: 22 - 45 years Sex: M+F 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 Health Status: healthy Age Group: mean 27 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/2972549/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP2E1 1060 CYP2A6 879 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/589038#sid=104234352	inconclusive
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625245#sid=104234352	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625246#sid=104234352	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625247#sid=104234352	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625248#sid=104234352	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625248#sid=104234352	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625251#sid=104234352	no [IC50 >10 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625171#sid=104234352

Sourcing

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

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
Chromatographic analysis of phenethylamine-antihistamine combinations using C8, C18 or cyano columns and micellar sodium dodecyl sulfate-pentanol mixtures.	2001 Apr	11340978
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
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.	2001 Nov	11736858
A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1) receptors.	2002 Jul	12065734
Differential cognitive effects of ebastine and (+)-chlorpheniramine in healthy subjects: correlation between cognitive impairment and plasma drug concentration.	2002 Mar	11874393
Uniformly sized molecularly imprinted polymer for d-chlorpheniramine. Evaluation of retention and molecular recognition properties in an aqueous mobile phase.	2002 Mar 1	12831185
[Roles of histamine receptors in pain perception: a study using receptors gene knockout mice].	2003 Nov	14569158
A case of probable codeine poisoning in a young infant after the use of a proprietary cough and cold medicine.	2004 Aug	15299176
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
Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic.	2004 Mar	15049392
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
Drug interaction between methamphetamine and antihistamines: behavioral changes and tissue concentrations of methamphetamine in rats.	2004 Nov 28	15556146
Allergy to dexchlorpheniramine. Study of a case.	2004 Sep-Oct	15456628
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
'Renal hypersensitivity' to inulin and IgA nephropathy.	2008 Oct	18535847
Fexofenadine hydrochloride in the treatment of allergic disease: a review.	2008 Sep 19	21436982
Memory in humans is unaffected by central H1-antagonism, while objectively and subjectively measured sedation is increased.	2010 Apr	20083393
[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
[Protocol for inducing infliximab tolerance in a patient with psoriatic spondylarthritis].	2010 Mar-Apr	20304368

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

Preferred 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

Dexchlorpheniramine [WHO-DD]

Common Name

English

Classification Tree Code System Code

LIVERTOX

289