Chlorphenamine
Clinical data | |
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Trade names | Chlor-Trimeton; Piriton; Chlor-Tripolon |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682543 |
Pregnancy category |
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Subcutaneous | |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 25 to 50% |
Protein binding | 72% |
Metabolism | Liver (CYP2D6) |
Elimination half-life | 13.9–43.4 hours[1] |
Excretion | Kidney |
Identifiers | |
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JSmol) | |
Solubility in water | 0.55 g/100 mL, liquid mg/mL (20 °C) |
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Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an
Common side effects include sleepiness, restlessness, and weakness. Other side effects may include
Chlorpheniramine was patented in 1948 and came into medical use in 1949.
Name
Chlorphenamine is the
while chlorpheniramine is the .Brand names include Chlor-Trimeton, Demazin, Allerest 12 Hour, Piriton, Chlorphen-12, Tylenol Cold/Allergy, and numerous others according to country.[2]
Medical uses
Combination products
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.[5] Chlorphenamine remains available with no such risk.
In the drug Coricidin, chlorphenamine is combined with the cough suppressant dextromethorphan. In the drug Cêgripe, chlorphenamine is combined with the analgesic paracetamol.[6]
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.[2]
Chlorphenamine produces less
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.[8] Chlorphenamine is rated as a "high burden" anticholinergic by experts on a semi-subjective scale.[9]
Pharmacology
Pharmacodynamics
Site | Ki (nM) | Species | Ref |
---|---|---|---|
SERT | 15.2 | Human | [11] |
NET | 1,440 | Human | [11] |
DAT | 1,060 | Human | [11] |
5-HT2A | 3,130 | Rat | [12] |
5-HT2C | 3,120 | Rat | [13] |
H1 | 2.5–3.0 | Human | [14][15] |
H2 | ND | ND | ND |
H3 | >10,000 | Rat | [16] |
H4 | 2,910 | Human | [17] |
M1 | 25,700 | Human | [18] |
M2 | 17,000 | Human | [18] |
M3 | 52,500 | Human | [18] |
M4 | 77,600 | Human | [18] |
M5 | 28,200 | Human | [18] |
hERG |
20,900 | Human | [19] |
Values are Ki, unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. Values at the hERGIC50 (nM).
are |
Chlorphenamine acts primarily as a potent H1
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).[11][24] It has only weak affinity for the norepinephrine and dopamine transporters (Kd = 1,440 nM and 1,060 nM, respectively).[11]
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.[25] 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.[26]
Pharmacokinetics
The
Chemistry
Chlorphenamine is an
Synthesis
There are several patented methods for the
A second method boom starts from pyridine, which undergoes alkylation by 4-chlorophenylacetonitrile,[28] giving 2-(4-chlorobenzyl)pyridine. Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives chlorphenamine.
References
- ^ S2CID 35759573.
- ^ a b c d e f g h "Chlorpheniramine". Drugs.com. American Society of Health-System Pharmacists. 26 July 2023. Archived from the original on 20 August 2023. Retrieved 20 August 2023.
- ISBN 9783527607495.
- ^ "Over-the-Counter Medicines for Allergies". HealthLink BC. Archived from the original on 15 July 2019. Retrieved 15 July 2019.
- ^ "Phenylpropanolamine (PPA) Information Page – FDA moves PPA from OTC" (Press release). US Food and Drug Administration. 23 December 2005. Archived from the original on 12 January 2009.
- ^ "Cêgripe". Cegripe.pt. Archived from the original on 25 June 2022. Retrieved 10 June 2022.
- ISBN 978-0-941901-21-5.
- PMID 25621434.
- PMID 25879993.
- ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 2 October 2020. Retrieved 14 August 2017.
- ^ PMID 9537821.
- S2CID 23311638.
- PMID 3139864.
- PMID 7925364.
- PMID 8335064.
- S2CID 83953993.
- from the original on 10 January 2023. Retrieved 21 January 2023.
- ^ S2CID 39502992.
- S2CID 40355762.
- PMID 15548781.
- S2CID 11849647.
- PMID 6086881.
- S2CID 21236268.
- S2CID 39627573.
- S2CID 2600032.
- PMID 4151898.
- ^ D. Papa, E. Schwenk, N. Sperber, U.S. patent 2,567,245 (1951)
- PMID 18918843.
- ^ D. Papa, E. Schwenk, N. Sperber, U.S. patent 2,676,964 (1954)