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Details

Stereochemistry RACEMIC
Molecular Formula C16H19ClN2.ClH
Molecular Weight 311.249
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHLORPHENIRAMINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=NOXNCSQBTYNMHD-UHFFFAOYSA-N
InChI=1S/C16H19ClN2.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C16H19ClN2
Molecular Weight 274.788
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

-6.116256E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
30.6 ng/mL
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1075.7 ng × h/mL
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
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
24.5 h
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
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
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
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

Doses

DosePopulationAdverse events​
5 mg single, intravenous
Dose: 5 mg
Route: intravenous
Route: single
Dose: 5 mg
Sources:
healthy, 27-40 years
n = 2
Health Status: healthy
Age Group: 27-40 years
Sex: M+F
Population Size: 2
Sources:
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:
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:
4 mg single, intravenous
Dose: 4 mg
Route: intravenous
Route: single
Dose: 4 mg
Sources:
unhealthy, 50-54 years
n = 2
Health Status: unhealthy
Age Group: 50-54 years
Sex: F
Population Size: 2
Sources:
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:
AEs

AEs

AESignificanceDosePopulation
Abdominal cramp 1 patient
4 mg single, intravenous
Dose: 4 mg
Route: intravenous
Route: single
Dose: 4 mg
Sources:
unhealthy, 50-54 years
n = 2
Health Status: unhealthy
Age Group: 50-54 years
Sex: F
Population Size: 2
Sources:
Diarrhea 1 patient
4 mg single, intravenous
Dose: 4 mg
Route: intravenous
Route: single
Dose: 4 mg
Sources:
unhealthy, 50-54 years
n = 2
Health Status: unhealthy
Age Group: 50-54 years
Sex: F
Population Size: 2
Sources:
Nausea 1 patient
4 mg single, intravenous
Dose: 4 mg
Route: intravenous
Route: single
Dose: 4 mg
Sources:
unhealthy, 50-54 years
n = 2
Health Status: unhealthy
Age Group: 50-54 years
Sex: F
Population Size: 2
Sources:
Tryptase increased 1 patient
4 mg single, intravenous
Dose: 4 mg
Route: intravenous
Route: single
Dose: 4 mg
Sources:
unhealthy, 50-54 years
n = 2
Health Status: unhealthy
Age Group: 50-54 years
Sex: F
Population Size: 2
Sources:
Urticaria 2 patients
4 mg single, intravenous
Dose: 4 mg
Route: intravenous
Route: single
Dose: 4 mg
Sources:
unhealthy, 50-54 years
n = 2
Health Status: unhealthy
Age Group: 50-54 years
Sex: F
Population Size: 2
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak [Ki 11 uM]
yes [Ki 191.2 uM]
yes [Ki 87.6 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
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
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Oral facial dyskinesia associated with prolonged use of antihistaminic decongestants.
1975 Sep 4
Skeletal muscle necrosis following membrane-active drugs plus serotonin.
1976 May
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Enhancement of morphine-induced hyperactivity by antihistaminic drugs in mice.
1986 Dec
Antagonism of drug-induced yawning and penile erections in rats.
1986 Mar 18
Histamine and hepatic glutathione in the mouse.
1987 May 25
A comparison of acrivastine versus chlorpheniramine in the treatment of chronic idiopathic urticaria.
1989
Drug-induced acute pulmonary edema--sequential changes in CT images.
1991 Nov-Dec
In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist mizolastine with H1 receptors in the rodent.
1995 May
Combining event rates from clinical trials: comparison of Bayesian and classical methods.
1996 May
The role of histaminergic-noradrenergic axis in naloxone-induced withdrawal symptoms in mice.
1996 Sep
[Dexchlorpheniramine-induced acute hepatitis: a case with positive rechallenge].
1998 Oct
Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats.
2000 Dec 22
A new model of allergic rhinitis in rats by topical sensitization and evaluation of H(1)-receptor antagonists.
2000 Jun
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.
2001 Nov
Ketoconazole potentiates terfenadine-induced apoptosis in human Hep G2 cells through inhibition of cytochrome p450 3A4 activity.
2002
Chlorphenamine.
2005 Aug 9-15
Carrier mediated transport of chlorpheniramine and chlorcyclizine across bovine olfactory mucosa: implications on nose-to-brain transport.
2005 Mar
Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice.
2005 Nov
Excitatory effect of histamine on neuronal activity of rat globus pallidus by activation of H2 receptors in vitro.
2005 Nov
Phase II study of gemcitabine, doxorubicin and paclitaxel (GAT) as first-line chemotherapy for metastatic breast cancer: a translational research experience.
2006 Mar 21
Histamine induces MUC5AC expression via a hCLCA1 pathway.
2007
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish.
2007 Apr
Allergic hemiglossitis as a unique case of food allergy: a case report.
2008 Mar 6
Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience.
2009 Jan 27
Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review.
2010 Dec
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study.
2010 Feb 21
Simultaneous determination of paracetamol, pseudoephedrine, dextrophan and chlorpheniramine in human plasma by liquid chromatography-tandem mass spectrometry.
2010 Mar 1
Two cases of h(2)-receptor antagonist hypersensitivity and cross-reactivity.
2011 Apr
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Sample Use Guides

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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:21:07 UTC 2023
Edited
by admin
on Fri Dec 15 15:21:07 UTC 2023
Record UNII
5S6VUP419V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CHLORPHENIRAMINE HYDROCHLORIDE
Common Name English
CHLORPHENIRAMINE HCL
Common Name English
CHLORPHENAMINE HYDROCHLORIDE
WHO-DD  
Common Name English
Chlorphenamine hydrochloride [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID60873070
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
CAS
56343-98-7
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
EVMPD
SUB122569
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
DRUG BANK
DBSALT001894
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
ECHA (EC/EINECS)
260-122-7
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
SMS_ID
100000145018
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
PUBCHEM
91813
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
FDA UNII
5S6VUP419V
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
NCI_THESAURUS
C87465
Created by admin on Fri Dec 15 15:21:07 UTC 2023 , Edited by admin on Fri Dec 15 15:21:07 UTC 2023
PRIMARY
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