Demazin
   HOME

TheInfoList



OR:

Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an
antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...
used to treat the symptoms of allergic conditions such as
allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...
(hay fever). It is taken by mouth. The medication takes effect within two hours and lasts for about 4-6. Common side effects include sleepiness, restlessness, and weakness. Other side effects may include
dry mouth Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...
and wheeziness. It is a
first-generation antihistamine H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of hi ...
and works by blocking the
H1 receptor The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the h ...
. Chlorpheniramine was patented in 1948 and came into medical use in 1949. It is available as a generic medication and
over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
.


Medical uses


Combination products

Chlorphenamine is often combined with phenylpropanolamine to form an
allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
medication with both
antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...
and
decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter ...
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 Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
hydrocodone Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe eno ...
. Chlorphenamine/
dihydrocodeine Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) (as in co-dydramol) or aspirin. It was developed in Germany in 1908 a ...
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 Coricidin, Coricidin 'D' (decongestant), or Coricidin HBP (for high blood pressure), is the name of an over-the-counter cough and cold drug containing dextromethorphan (a cough suppressant) and chlorpheniramine maleate (an antihistamine). Introdu ...
, chlorphenamine is combined with the cough suppressant
dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...
. In the drug Cêgripe, chlorphenamine is combined with the analgesic paracetamol.


Side effects

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. Chlorphenamine produces less sedation than other
first-generation antihistamine H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of hi ...
s. A large study on people 65 years old or older, linked the development of Alzheimer's disease and other forms of dementia to the "higher cumulative" use of chlorphenamine and other first-generation antihistamines, due to their
anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...
properties.


Pharmacology


Pharmacodynamics

Chlorphenamine acts primarily as a potent H1
antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...
. It is specifically a potent inverse agonist of the
histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered ...
H1 receptor. The drug is also commonly described as possessing weak
anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...
activity by acting as an antagonist of the
muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...
s. The
dextrorotatory Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...
stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
,
dexchlorpheniramine Dexchlorpheniramine (trade name Polaramine) is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of chlorpheniramine. It c ...
, has been reported to possess Kd values of 15 nM for the H1 receptor and 1,300 nM for the muscarinic acetylcholine receptors in human brain tissue. The smaller the Kd value, the greater the binding affinity of the ligand for its target. In addition to acting as an inverse agonist at the H1 receptor, chlorphenamine has been found to act as a
serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to incre ...
(Kd = 15.2 nM for the
serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...
). It has only weak affinity for the
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
and
dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...
s (Kd = 1,440 nM and 1,060 nM, respectively). A similar antihistamine,
brompheniramine Brompheniramine, sold under the brand name Dimetapp among others, is a first-generation antihistamine drug of the propylamine (alkylamine) class. It is indicated for the treatment of the symptoms of the common cold and allergic rhinitis, such ...
, led to the discovery of the
selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...
(SSRI) zimelidine. A study found that dexchlorphenamine had Ki values for the human cloned H1 receptor of 2.67 to 4.81 nM while levchlorphenamine had Ki values of 211 to 361 nM for this receptor, indicating that dexchlorphenamine is the active enantiomer. Another study found that dexchlorphenamine had a Ki value of 20 to 30 μM for the
muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...
using rat brain tissue while levchlorphenamine had a Ki value of 40 to 50 μM for this receptor, indicating that both enantiomers have very low affinity for it.


Pharmacokinetics

The
elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of chlorphenamine has variously ranged between 13.9 and 43.4 hours in adults following a single dose in clinical studies.


Chemistry

Chlorphenamine is an alkylamine and is a part of a series of antihistamines including
pheniramine Pheniramine (trade name Avil among others) is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It has relatively strong sedative effects, and may sometimes be used off-label as an ...
(Naphcon) and its halogenated derivatives including fluorpheniramine, dexchlorphenamine (Polaramine),
brompheniramine Brompheniramine, sold under the brand name Dimetapp among others, is a first-generation antihistamine drug of the propylamine (alkylamine) class. It is indicated for the treatment of the symptoms of the common cold and allergic rhinitis, such ...
(Dimetapp),
dexbrompheniramine Dexbrompheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of brompheniramine. It was formerly marketed in comb ...
(Drixoral), deschlorpheniramine, and iodopheniramine. The halogenated alkylamine antihistamines all exhibit
optical isomerism In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...
, and chlorphenamine in the indicated products is racemic chlorphenamine
maleate Maleic acid or ''cis''-butenedioic acid is an organic compound that is a dicarboxylic acid, a molecule with two carboxyl groups. Its chemical formula is HO2CCH=CHCO2H. Maleic acid is the ''cis''-isomer of butenedioic acid, whereas fumaric acid ...
, whereas dexchlorphenamine is the
dextrorotary Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...
stereoisomer.


Synthesis

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 Sodium amide, commonly called sodamide (systematic name sodium azanide), is the inorganic compound with the formula . It is a salt composed of the sodium cation and the azanide anion. This solid, which is dangerously reactive toward water, is white ...
to form 4-chlorophenyl(2-pyridyl)acetonitrile. Alkylating this with 2-dimethylaminoethylchloride in the presence of
sodium amide Sodium amide, commonly called sodamide (systematic name sodium azanide), is the inorganic compound with the formula . It is a salt composed of the sodium cation and the azanide anion. This solid, which is dangerously reactive toward water, is white ...
gives γ-(4-chlorphenyl)-γ-cyano-''N'',''N''-dimethyl-2-pyridinepropanamine, the
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...
and decarboxylation of which lead to chlorphenamine. A second method boom starts from
pyridine Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a ...
, 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 ''chlorpheniramine'' is the and former . 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 Tylenol may refer to: * Paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decr ...
Cold/Allergy.


References

{{Portal bar, Medicine Antidepressants Anxiolytics Chlorobenzenes CYP2D6 inhibitors H1 receptor antagonists Local anesthetics Muscarinic antagonists 2-Pyridyl compounds Serotonin reuptake inhibitors Sigma receptor ligands Sodium channel blockers World Health Organization essential medicines