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

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	( + / - )

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
Oral facial dyskinesia associated with prolonged use of antihistaminic decongestants.	1975 Sep 4	239337
Skeletal muscle necrosis following membrane-active drugs plus serotonin.	1976 May	6632
Aplastic anaemia after prolonged treatment with chlorpheniramine.	1977 Mar 5	65643
Jaundice during cyproheptadine treatment.	1978 Mar 25	630329
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.	1978 Oct 7	709472
The I antigen as an immune complex receptor in a case of haemolytic anaemia induced by an antihistaminic agent.	1981 Sep	6115667
Reaction to phenylpropalamine/chlorpheniramine/belladonna compound in a women with unrecognised autonomic dysfunction.	1982 Jul 31	6124702
Enhancement of morphine-induced hyperactivity by antihistaminic drugs in mice.	1986 Dec	2881522
Antagonism of drug-induced yawning and penile erections in rats.	1986 Mar 18	2872065
Antihistaminics enhance morphine-, but not amphetamine- and scopolamine-induced hyperactivity in mice.	1987	2892221
Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists.	1987 Jun	2884595
Histamine and hepatic glutathione in the mouse.	1987 May 25	2884542
Chronic chlorpheniramine therapy: subsensitivity, drug metabolism, and compliance.	1987 Nov	3688558
Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis.	1988 Nov	3057041
Antihistaminic-opioid combination: effect on locomotor activity in mice.	1988 Sep-Oct	3253717
A comparison of acrivastine versus chlorpheniramine in the treatment of chronic idiopathic urticaria.	1989	2569998
[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
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.	1993 Dec	7508328
Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi.	1994 Jan	8111568
Benefit/risk ratio of the antihistamines (H1-receptor antagonists) terfenadine and chlorpheniramine in children.	1994 Jun	8201490
In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist mizolastine with H1 receptors in the rodent.	1995 May	7612054
Combining event rates from clinical trials: comparison of Bayesian and classical methods.	1996 May	8740323
The role of histaminergic-noradrenergic axis in naloxone-induced withdrawal symptoms in mice.	1996 Sep	8870037
[Dexchlorpheniramine-induced acute hepatitis: a case with positive rechallenge].	1998 Oct	9854210
Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.	2008 Dec	19075512
Rare case of "red man" syndrome in a female patient treated with oral vancomycin for Clostridium difficile diarrhoea.	2009	21886654
Investigation of enantiomeric separation of basic drugs by capillary electrophoresis using clindamycin phosphate as a novel chiral selector.	2009 Aug	19621372
Suspected anaphylactic reactions associated with anaesthesia.	2009 Feb	19143700
Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience.	2009 Jan 27	19165196
A computational approach to studying monomer selectivity towards the template in an imprinted polymer.	2009 Jul	19132418
Block of HERG k channel by classic histamine h(1) receptor antagonist chlorpheniramine.	2009 Jun	19885040
Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer.	2009 Mar 10	19223898
[Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine].	2009 May 15	19624990
Continuous quinacrine treatment results in the formation of drug-resistant prions.	2009 Nov	19956709
Hepatotoxicity induced by methimazole in a previously healthy patient.	2009 Sep	19534646
Retro-orbital oedema and transient blindness following endoscopic oesophagogastroduodenoscopy: a case report.	2009 Sep 2	19918358
Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review.	2010 Dec	21175434
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.	2010 Dec	21158687
Differential responding of autonomic function to histamine H₁ antagonism in irritable bowel syndrome.	2010 Dec	20667004
Transport of phenylethylamine at intestinal epithelial (Caco-2) cells: mechanism and substrate specificity.	2010 Feb	19962438
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	20170547
Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria.	2010 Jul 27	20668549
Simultaneous determination of paracetamol, pseudoephedrine, dextrophan and chlorpheniramine in human plasma by liquid chromatography-tandem mass spectrometry.	2010 Mar 1	20133213
Evaluation of the enantioseparation capability of the novel chiral selector clindamycin phosphate towards basic drugs by micellar electrokinetic chromatography.	2010 Mar 12	20132938
Two cases of h(2)-receptor antagonist hypersensitivity and cross-reactivity.	2011 Apr	21461253
The discovery of phthalazinone-based human H1 and H3 single-ligand antagonists suitable for intranasal administration for the treatment of allergic rhinitis.	2011 Apr 14	21381763
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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:09:18 GMT 2023` Edited by `admin` on `Sat Dec 16 17:09:18 GMT 2023`
Record UNII	3U6IO1965U
Record Status	`Validated (UNII)`
Record Version

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Classification Tree Code System Code

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