Chlorphenamine Clinical data Trade names Chlor-Trimeton; Piriton AHFS/ Drugs.com Monograph MedlinePlus a682543 Pregnancy category Routes of administration By mouth, IV, IM, SC ATC code Legal status Legal status
Pharmacokinetic data Bioavailability 25 to 50% Protein binding 72% Metabolism Liver ( CYP2D6) Elimination 13.9-43.4 hours  Excretion Kidney Identifiers
N, N-dimethyl-3-(pyridin-2-yl)-propan-1-amine CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard ( EPA) ECHA InfoCard 100.004.596 Chemical and physical data Formula C 16 H 19 Cl N 2 Molar mass g·mol -1 3D model ( JSmol) Solubility in water 0.55 g/100 mL, liquid mg/mL (20 °C)
(what is this?) (verify) Chlorphenamine ( CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken by mouth.  The medication takes effect within 6 hours and lasts for about a day.  
Common side effects include sleepiness, restlessness, and weakness.
Other side effects may include  dry mouth and wheeziness. It is a  first-generation antihistamine and works by blocking the H1 receptor. 
Chlorphenamine was patented in 1948 and came into medical use in 1949.
It is available as a  generic medication and over the counter.  
Chlorphenamine is often combined with
phenylpropanolamine to form an allergy medication with both antihistamine and decongestant properties, though phenylpropanolamine is no longer available in the US after studies showed it increased the risk of stroke in young women. Chlorphenamine remains available with no such risk.
Chlorphenamine may be combined with the
opioid hydrocodone. Chlorphenamine/ dihydrocodeine immediate-release syrups are also marketed. The antihistamine is helpful in cases where allergy or common cold is the reason for the cough; it is also a potentiator of opioids, allowing enhanced suppression of cough, analgesia, and other effects from a given quantity of the drug by itself. In various places in the world, cough and cold preparations containing codeine and chlorphenamine are available.
In the drug
Coricidin, chlorphenamine is combined with the cough suppressant dextromethorphan.
The adverse effects include drowsiness, dizziness, confusion, constipation, anxiety, nausea, blurred vision, restlessness, decreased coordination, dry mouth, shallow breathing, hallucinations, irritability, problems with memory or concentration, tinnitus and trouble urinating.
A large study on people 65 years old or older, linked the development of
Alzheimer's disease and other forms of dementia to the use of chlorphenamine and other first-generation antihistamines, due to their anticholinergic properties. 
i (nM) Species
5-HT 2A 3,130
5-HT 2C 3,120
H 1 2.5-3.0
H 3 >10,000
H 4 2,910
M 1 25,700
M 2 17,000
M 3 52,500
M 4 77,600
M 5 28,200
 Values are K i, unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. Values at the and mAChRs are hERG IC (nM).
Chlorphenamine acts primarily as a potent H
1 antihistamine. It is specifically a potent inverse agonist of the histamine H. 1 receptor  The drug is also commonly described as possessing weak  anticholinergic activity by acting as an antagonist of the muscarinic acetylcholine receptors. The dextrorotatory stereoisomer, dexchlorpheniramine, has been reported to possess K d values of 15 nM for the H 1 receptor and 1,300 nM for the muscarinic acetylcholine receptors in human brain tissue.  The smaller the K  d value, the greater the binding affinity of the ligand for its target.
In addition to acting as an
inverse agonist at the H 1 receptor, chlorphenamine has been found to act as a serotonin reuptake inhibitor (K d = 15.2 nM for the serotonin transporter).  It has only weak affinity for the  norepinephrine and dopamine transporters (K d = 1,440 nM and 1,060 nM, respectively). A similar antihistamine,  brompheniramine, led to the discovery of the selective serotonin reuptake inhibitor (SSRI) zimelidine.
A study found that dexchlorphenamine had K
i values for the human cloned H of 2.67 to 4.81 nM while levchlorphenamine had K 1 receptor i values of 211 to 361 nM for this receptor, indicating that dexchlorphenamine is the active enantiomer. Another study found that dexchlorphenamine had a K  i value of 20 to 30 ?M for the muscarinic acetylcholine receptor using rat brain tissue while levchlorphenamine had a K i value of 40 to 50 ?M for this receptor, indicating that both enantiomers have very low affinity for it. 
elimination half-life of chlorphenamine has variously ranged between 13.9 and 43.4 hours in adults following a single dose in clinical studies. 
Chlorphenamine is an
alkylamine and is a part of a series of antihistamines including pheniramine (Naphcon) and its halogenated derivatives including fluorpheniramine, dexchlorphenamine (Polaramine), brompheniramine (Dimetapp), dexbrompheniramine (Drixoral), deschlorpheniramine, and iodopheniramine. The halogenated alkylamine antihistamines all exhibit optical isomerism, and chlorphenamine in the indicated products is racemic chlorphenamine maleate, whereas dexchlorphenamine is the dextrorotary stereoisomer.
There are several patented methods for the
synthesis of chlorphenamine. In one example, 4-chlorophenylacetonitrile is reacted with 2-chloropyridine in the presence of sodium amide to form 4-chlorophenyl(2-pyridyl)acetonitrile. Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives ?-(4-chlorphenyl)-?-cyano- N, N-dimethyl-2-pyridinepropanamine, the hydrolysis and decarboxylation of which lead to chlorphenamine.
A second method starts from
pyridine, which undergoes alkylation by 4-chlorophenylacetonitrile, giving 2-(4-chlorobenzyl)pyridine. Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives chlorphenamine.
Society and culture
Names Chlorphenamine is the while INN chlorpheniramine is the and former USAN .
Brand names have included Demazin, Allerest 12 Hour,
Codral Nighttime, Chlornade, Contac 12 Hour, Exchange Select Allergy Multi-Symptom, A. R. M. Allergy Relief, Ordrine, Ornade Spansules, Piriton, Teldrin, Triaminic, and Tylenol Cold/Allergy.
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