CHLORPHENIRAMINE

US Approved OTC

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H19ClN2
Molecular Weight	274.788
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCC(C1=CC=C(Cl)C=C1)C2=CC=CC=N2

InChI

InChIKey=SOYKEARSMXGVTM-UHFFFAOYSA-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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6383755 | https://www.drugs.com/cdi/chlorpheniramine.html | https://www.ncbi.nlm.nih.gov/pubmed/16413139

Chlorpheniramine is an antihistamine. Chlorpheniramine 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. Chlorpheniramine is used for relieving symptoms of sinus congestion, sinus pressure, runny nose, watery eyes, itching of the nose and throat, and sneezing due to upper respiratory infections (eg, colds), allergies, and hay fever. In addition to being a histamine H1 receptor (HRH1) antagonist, chlorphenamine has been shown to work as a serotonin-norepinephrine reuptake inhibitor or SNRI.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Plasmodium falciparum (isolate K1 / Thailand) 8 Target ID: CHEMBL612856 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16750932	Inhibitor 8297	136.0 µM [IC50]
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2879912 \| https://www.ncbi.nlm.nih.gov/pubmed/18363822	Antagonist 2778	12.0 nM [IC50]
Sodium-dependent serotonin transporter 40 Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16413139 \| https://www.ncbi.nlm.nih.gov/pubmed/4390069 \| https://www.drugbank.ca/drugs/DB01114 \| https://www.ncbi.nlm.nih.gov/pubmed/18363822	Inhibitor 8297	15.2 nM [Kd]
Sodium-dependent dopamine transporter 42 Target ID: Q01959 Gene ID: 6531.0 Gene Symbol: SLC6A3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18363822 \| https://www.drugbank.ca/drugs/DB01114	Inhibitor 8297	203.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: http://www.rxlist.com/chlor-trimeton-side-effects-drug-center.htm	Primary		Approved 8429	Chlor-Trimeton Approved Use Uses temporarily relieves the following symptoms due to hay fever or other upper respiratory allergies: sneezing runny nose itchy, watery eyes itching of the nose or throat Launch Date 1950

C_max

Value	Dose	Analyte	Population
30.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	8 mg 2 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
32.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	4 mg 4 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
25.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	8 mg 2 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
13.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7069073/	0.12 mg/kg bw single, oral dose: 0.12 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
1075.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	8 mg 2 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1202.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	4 mg 4 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
961 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	8 mg 2 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
246.16 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7069073/	0.12 mg/kg bw single, oral dose: 0.12 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
24.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	8 mg 2 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
25.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	4 mg 4 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
25.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7104467/	8 mg 2 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
13.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7069073/	0.12 mg/kg bw single, oral dose: 0.12 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	CHLORPHENIRAMINE serum	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
5 mg single, intravenous Dose: 5 mg Route: intravenous Route: single Dose: 5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7106172	healthy, 27-40 years n = 2 Health Status: healthy Age Group: 27-40 years Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/7106172	Sources: https://pubmed.ncbi.nlm.nih.gov/7106172
48 mg 1 times / day multiple, oral Studied dose Dose: 48 mg, 1 times / day Route: oral Route: multiple Dose: 48 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4008807/	unhealthy, 34 years (range: 13-52 years) n = 10 Health Status: unhealthy Age Group: 34 years (range: 13-52 years) Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/4008807/	Sources: https://pubmed.ncbi.nlm.nih.gov/4008807/
4 mg single, intravenous Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	unhealthy, 50-54 years n = 2 Health Status: unhealthy Age Group: 50-54 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	Other AEs: Tryptase increased, Urticaria... Other AEs: Tryptase increased (1 patient) Urticaria (2 patients) Abdominal cramp (1 patient) Nausea (1 patient) Diarrhea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31852144

AEs

AE	Significance	Dose	Population
Abdominal cramp	1 patient	4 mg single, intravenous Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	unhealthy, 50-54 years n = 2 Health Status: unhealthy Age Group: 50-54 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/31852144
Diarrhea	1 patient	4 mg single, intravenous Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	unhealthy, 50-54 years n = 2 Health Status: unhealthy Age Group: 50-54 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/31852144
Nausea	1 patient	4 mg single, intravenous Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	unhealthy, 50-54 years n = 2 Health Status: unhealthy Age Group: 50-54 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/31852144
Tryptase increased	1 patient	4 mg single, intravenous Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	unhealthy, 50-54 years n = 2 Health Status: unhealthy Age Group: 50-54 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/31852144
Urticaria	2 patients	4 mg single, intravenous Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31852144	unhealthy, 50-54 years n = 2 Health Status: unhealthy Age Group: 50-54 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/31852144

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE1 306 MATE2 263	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	weak [Ki 11 uM]
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 191.2 uM]
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 87.6 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11284026/ Page: 6.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874352/	yes		likely (co-administration study) Comment: The two poor metabolizers with respect to CYP2D6 were included as controls in the present study, as quinidine would not be expected to produce any further inhibition of CYP2D6 in those subjects. However, a slight decrease in AUC(0,∞) and a slight increase in CLoral was observed for both the (R)-(−)- and the (S)-(+)-enantiomers following administration of quinidine, although it is not possible to draw a firm conclusion from such a small number of subjects Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874352/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766741/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY544662	https://www.001chemical.com/chem/25523-97-1
Alfa Chemistry	1185054-60-7	https://www.alfa-chemistry.com/cas_1185054-60-7.htm
Aurum Pharmatech LLC	T7375	http://www.Aurumpharmatech.com/Product/ProductDetails/T7375
BLD Pharm	BD01108280	http://www.bldpharm.com/products/132-22-9.html
BOC Sciences	132-22-9	https://www.bocsci.com/chlorpheniramine-cas-132-22-9-item-332358.html
BioSynth	W-108317	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-108317.html
Chemspace	CSSB00025765201	https://chem-space.com/CSSB00025765201
Clearsynth	CS-T-51081	https://www.clearsynth.com/en/CST51081.html
Finetech	FT-0665002	http://www.finetechnology-ind.com/prod/detail/pub/1185054-60-7.html
Finetech	FT-0772034	http://www.finetechnology-ind.com/prod/detail/pub/25523-97-1.html
MolPort	MolPort-002-507-837	https://www.molport.com/shop/molecule-link/MolPort-002-507-837
Molcore	MC544662	https://www.molcore.com/product/25523-97-1
Parchem	28520	http://www.parchem.com/chemical-supplier-distributor/Chlorpheniramine-Maleate-B-P--018520.aspx
Smolecule	S525766	http://www.smolecule.com/products/s525766
Smolecule	S793296	https://www.smolecule.com/products/s793296
Synblock Inc	SB19135	http://www.synblock.com/product/132-22-9.html
THE BioTek	bt-267099	https://www.thebiotek.com/product/inhibitors/bt-267099
iChemical	EBD3323802	http://www.ichemical.com/products/132-22-9.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-2363896855	https://mcule.com/MCULE-2363896855/

PubMed

Title	Date	PubMed
Toxic epidermal necrolysis associated with pentazocine therapy and severe reversible renal failure.	1973 Mar	4712825
Cholinesterase inhibition by phenothiazine and nonphenothiazine antihistaminics: analysis of its postulated role in synergizing organophosphate toxicity.	1975 Feb	236606
The I antigen as an immune complex receptor in a case of haemolytic anaemia induced by an antihistaminic agent.	1981 Sep	6115667
[Antimycobacterial antihistaminics].	1989 Aug	2513793
Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography.	1993 Apr	8101246
Central nervous system effects of H1-receptor antagonists in the elderly.	1999 Feb	10071518
[An exceptional case of hypersensitivity to actinomycin D. Case report and review of the literature].	2001 Sep-Oct	11794853
Ketoconazole potentiates terfenadine-induced apoptosis in human Hep G2 cells through inhibition of cytochrome p450 3A4 activity.	2002	12244568
[Molecular diversity of organic cation transporter (OCT) mediating renal excretion of drugs].	2002 Nov	12440152
Clinical pharmacology of H1-antihistamines in the skin.	2002 Nov	12417888
[A successfully treated case of intraoperative latex anaphylaxis during abdominal aorta aneurysm resection].	2003 Jan	12632613
Involvement of histamine H3 receptors in scratching behaviour in mast cell-deficient mice.	2003 Jul	12890190
Adrenaline given outside the context of life threatening allergic reactions.	2003 Mar 15	12637407
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
Up-regulation of histamine H(1) receptors in an allergic rat nasal mucosa model.	2004 Mar	15054595
Differentiating midazolam over-sedation from neurological damage in the intensive care unit.	2005 Feb	15693964
Cutaneous adverse drug reaction to oral chlorphenamine detected with patch testing.	2005 Jan	15701135
Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice.	2005 Nov	16202530
Allergic hemiglossitis as a unique case of food allergy: a case report.	2008 Mar 6	18321388
Investigation of enantiomeric separation of basic drugs by capillary electrophoresis using clindamycin phosphate as a novel chiral selector.	2009 Aug	19621372
A computational approach to studying monomer selectivity towards the template in an imprinted polymer.	2009 Jul	19132418
Simultaneous determination of paracetamol, pseudoephedrine, dextrophan and chlorpheniramine in human plasma by liquid chromatography-tandem mass spectrometry.	2010 Mar 1	20133213
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

Tablets or syrup: 4 mg orally every 4 to 6 hours. Sustained-release: 8 to 16 mg orally every 8 to 12 hours as needed or 16 mg orally once a day as needed. Maximum dose 32 mg/day.

Route of Administration: Oral

In Vitro Use Guide

Chlorpheniramine inhibits the [3H]mepyramine binding to the histamine H1 receptor in guinea pig cortex with IC50 of 8.8 nM.

Name

Type

Language

CHLORPHENIRAMINE

Common Name

English

CHLORPHENIRAMINE [VANDF]

Common Name

English

CHLORPHENIRAMINE [MI]

Common Name

English

CHLORPHENIRAMINE COMPONENT OF TUZISTRA

Brand Name

English

chlorphenamine [INN]

Common Name

English

Chlorphenamine [WHO-DD]

Common Name

English

CHLORPHENIRAMINE [HSDB]

Common Name

English

CLOFENIRAMINA

Brand Name

English

783AHI015X

Common Name

English

2-(P-CHLORO-.ALPHA.-(2-(DIMETHYLAMINO)ETHYL)BENZYL)PYRIDINE

Common Name

English

CHLORPHENAMINE

Official Name

English

TUZISTRA COMPONENET OF CHLORPHENIRAMINE

Brand Name

English

Classification Tree Code System Code

WHO-ATC

R06AB04