Chlorphenamine

From Wikipedia, the free encyclopedia
(Redirected from Chlorpheniramine)
Jump to navigation Jump to search
Not to be confused with Chloropyramine.

Chlorphenamine
File:Chlorphenamine.svg
File:Chlorpheniramine for veterinary use.jpg
Clinical data
Trade namesChlor-Trimeton; Piriton; Chlor-Tripolon; Allergex
AHFS/Drugs.comMonograph
MedlinePlusa682543
Pregnancy
category
  • AU: A
Routes of
administration		Oral, intravenous, intramuscular, subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability25 to 50%
Protein binding72%
MetabolismLiver (CYP2D6)
Elimination half-life13.9–43.4 hours[1]
ExcretionKidney
Identifiers
  • 3-(4-Chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)-propan-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
CompTox Dashboard (EPA)
  • {{#property:P3117}}Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value).
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC16H19ClN2
Molar mass274.79 g·mol−1
3D model (JSmol)
Solubility in water0.55 g/100 mL, liquid mg/mL (20 °C)
  • Clc1ccc(cc1)C(c2ncccc2)CCN(C)C
  • 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 checkY
  • Key:SOYKEARSMXGVTM-UHFFFAOYSA-N checkY
 ☒NcheckY (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).[2] It is taken orally (by mouth).[2] The medication takes effect within two hours and lasts for about 4–6 hours.[2] It is a first-generation antihistamine and works by blocking the histamine H1 receptor.[2]

Common side effects include sleepiness, restlessness, and weakness. Other side effects may include dry mouth and wheeziness.[2]

Chlorpheniramine was patented in 1948 and came into medical use in 1949.[3] It is available as a generic medication and over the counter.[2][4]

In 2023, it was the 318th most commonly prescribed medication in the United States, with more than 200,000 prescriptions.[5]

Medical uses

[edit | edit source]

Combination products

[edit | edit source]

Chlorphenamine is often combined with phenylpropanolamine to form an allergy medication with both antihistamine and decongestant properties, although phenylpropanolamine was removed from the U.S. market per studies concluding that it increased the risk of stroke in young women.[6] Vernate was a trade name of one such product available in the U.S. prior to the FDA ban; it was manufactured by Tutag and was among the medications prescribed to Elvis Presley.[7]

In the drug Coricidin, chlorphenamine is combined with the cough suppressant dextromethorphan. In the drug Cêgripe, chlorphenamine is combined with the analgesic paracetamol (also known as acetaminophen, sold as Tylenol).[8]

Side effects

[edit | edit source]

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.[2]

Chlorphenamine produces less sedation than other first-generation antihistamines.[9]

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 properties.[10] Chlorphenamine is rated as a "high burden" anticholinergic by experts on a semi-subjective scale.[11] This is inconsistent with the in vitro experiments showing low affinity to muscarinic acetylcholine receptors (see below).

Pharmacology

[edit | edit source]

Pharmacodynamics

[edit | edit source]
Chlorphenamine[12]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 15.2 Human [13]
NETTooltip Norepinephrine transporter 1,440 Human [13]
DATTooltip Dopamine transporter 1,060 Human [13]
5-HT2A 3,130 Rat [14]
5-HT2C 3,120 Rat [15]
H1 2.5–3.0 Human [16][17]
H2 ND ND ND
H3 >10,000 Rat [18]
H4 2,910 Human [19]
M1 25,700 Human [20]
M2 17,000 Human [20]
M3 52,500 Human [20]
M4 77,600 Human [20]
M5 28,200 Human [20]
hERGTooltip Human Ether-à-go-go-Related Gene 20,900 Human [21]
Values are Ki, unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. Values at the mAChRsTooltip muscarinic acetylcholine receptors and hERGTooltip Human Ether-à-go-go-Related Gene are IC50 (nM).

Chlorphenamine acts primarily as a potent H1 antihistamine. It is specifically a potent inverse agonist of the histamine H1 receptor.[22][23] 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 Kd values of 15 nM for the H1 receptor and 1,300 nM for the muscarinic acetylcholine receptors in human brain tissue.[24][25] 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 (Kd = 15.2 nM for the serotonin transporter).[13][26] It has only weak affinity for the norepinephrine and dopamine transporters (Kd = 1,440 nM and 1,060 nM, respectively).[13]

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.[27] Another study found that dexchlorphenamine had a Ki value of 20 to 30 μM for the muscarinic acetylcholine receptor 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.[28]

Pharmacokinetics

[edit | edit source]

The elimination half-life of chlorphenamine has variously ranged between 13.9 and 43.4 hours in adults following a single dose in clinical studies.[1]

Chemistry

[edit | edit source]

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.

Synthesis

[edit | edit source]

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 γ-(4-chlorphenyl)-γ-cyano-N,N-dimethyl-2-pyridinepropanamine, the hydrolysis and decarboxylation of which lead to chlorphenamine.

File:Chlorpheniramine synthesis.png
Chlorpheniramine synthesis[29]

A second method boom starts from pyridine, which undergoes alkylation by 4-chlorophenylacetonitrile,[30] giving 2-(4-chlorobenzyl)pyridine. Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives chlorphenamine.

File:Chlorpheniramine synthesis 2.png
Chlorpheniramine synthesis[31]

Society and culture

[edit | edit source]

Names

[edit | edit source]

Chlorphenamine is the INNTooltip International Nonproprietary Name while chlorpheniramine is the USANTooltip United States Adopted Name and former BANTooltip British Approved Name.

Brand names include Chlor-Trimeton, Demazin, Allerest 12 Hour, Piriton, Chlorphen-12, Tylenol Cold/Allergy, and numerous others according to country.[2]

References

[edit | edit source]
  1. ^ a b Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  2. ^ a b c d e f g h Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  3. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  4. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  5. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  6. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  7. ^ https://www.jodrugs.com/tradenames/167408-vernate.aspx Information on defunct drug Vernate
  8. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  9. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  10. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  11. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  12. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  13. ^ a b c d e Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  14. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  15. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  16. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  17. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  18. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  19. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  20. ^ a b c d e Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  21. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  22. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  23. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  24. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  25. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  26. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  27. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  28. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  29. ^ D. Papa, E. Schwenk, N. Sperber, U.S. patent 2,567,245 (1951)
  30. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  31. ^ D. Papa, E. Schwenk, N. Sperber, U.S. patent 2,676,964 (1954)

Lua error in mw.title.lua at line 392: bad argument #2 to 'title.new' (unrecognized namespace name 'Portal').

Retrieved from "http://70.231.62.181/index.php?title=Chlorphenamine&oldid=1458212"