Misplaced Pages

Clemastine

Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a682542
Routes of administration	Oral
ATC code	D04AA14 (WHO) R06AA04 (WHO)
Legal status
Legal status	In general: Over-the-counter (OTC)
Pharmacokinetic data
Bioavailability	39.2%
Metabolism	Hepatic
Elimination half-life	21.3 hours
Excretion	Renal
Identifiers
IUPAC name (2R)-2-{2-ethyl}-1-methylpyrrolidine
CAS Number	15686-51-8
PubChem CID	26987
IUPHAR/BPS	6063
DrugBank	DB00283
ChemSpider	25129
UNII	95QN29S1ID
KEGG	D03535
ChEBI	CHEBI:3738
ChEMBL	ChEMBL1626
CompTox Dashboard (EPA)	DTXSID2022832
Chemical and physical data
Formula	C21H26ClNO
Molar mass	343.90 g·mol
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)(OCC2N(C)CCC2)(c3ccccc3)C
InChI InChI=1S/C21H26ClNO/c1-21(17-7-4-3-5-8-17,18-10-12-19(22)13-11-18)24-16-14-20-9-6-15-23(20)2/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3/t20-,21-/m1/s1 Key:YNNUSGIPVFPVBX-NHCUHLMSSA-N
(verify)

Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects. Like all first-generation antihistamines, it is sedating.

Patented in 1960, it came into medical use in 1967.

Medical uses

Clemastine is used to relieve hay fever and allergy symptoms, including sneezing; runny nose; and red, itchy, tearing eyes. Prescription strength clemastine is also used to relieve the itching and swelling of hives.

Side effects

Overdosage symptoms are paradoxical, ranging from CNS depression to stimulation. Stimulation is most common in children, and is usually followed by excitement, hallucinations, ataxia, loss of coordination, muscle twitching, athetosis, hyperthermia, cyanosis, convulsions, tremors, and hyperreflexia. This may be followed by postictal depression and cardiovascular/respiratory arrest. Other common overdose symptoms include dry mouth, fixed dilated pupils, flushing of the face, and pyrexia. In adults, overdose usually leads to CNS depression, ranging from drowsiness to coma.

Continuous and/or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people.

Pharmacology

Clemastine is an antihistamine with anticholinergic and sedative effects. Antihistamines competitively bind to histamine receptor sites, thus reducing the neurotransmitter's effects. Effects of histamine (which are countered by antihistamines) include:

• Increased capillary permeability
• Increased capillary dilatation
• Edema (i.e., swelling)
• Pruritus (Itch)
• Gastrointestinal/respiratory smooth muscle constriction

Clemastine inhibits both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, the drug can produce paradoxical effects, including CNS stimulation or depression.

Most antihistamines exhibit some type of anticholinergic activity. Antihistamines act by competitively binding to H₁-receptor sites, thus blocking the binding of endogenous histamine. Antihistamines do not chemically inactivate or prevent the normal release of histamine.

Clemastine does also act as FIASMA (functional inhibitor of acid sphingomyelinase).

Clemastine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations are attained in 2–4 hours. Antihistamines are thought to be metabolized in the liver, mostly by mono-/didemethylation and glucuronide conjugation. It is an inhibitor of cytochrome P450 CYP2D6 and may interfere with other drugs metabolized by this isozyme.

Mechanism of action

Clemastine is a selective histamine H₁ antagonist. It binds to the histamine H₁ receptor, thus blocking the action of endogenous histamine, which leads to temporary relief of the negative symptoms caused by histamine.

Society and culture

Clemastine is an OTC drug, and is available under many names and dosage forms worldwide. Most common brand name is Tavegyl.

Research

Clemastine has been studied for its potential to treat several psychiatric and neurological disorders, including possibly promoting remyelination and myelin repair in conditions like multiple sclerosis (MS). Early phase II clinical trials showed promise for promoting remyelination in patients with MS, with clemastine improving nerve conduction velocity in the optic nerve. However, a clinical trial (TRAP-MS) was halted in early 2024 after researchers found the disability progression was occurring at a significantly faster rate than anticipated in three participants with MS receiving clemastine.

References

1. "Clemastine". DrugBank.com.
2. "Perspectives on Second-Generation OTC Antihistamines". Pharmacy Times. 2012-03-30. Archived from the original on 2012-05-01.
3. Krouse JH (April 2008). "Allergic rhinitis--current pharmacotherapy". Otolaryngologic Clinics of North America. 41 (2): 347–58, vii. doi:10.1016/j.otc.2007.11.014. PMID 18328373.
4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN 9783527607495.
5. "Clemastine". MedlinePlus.
6. "Clemastine Side Effects: Common, Severe, Long Term". Drugs.com. 23 January 2023. Retrieved 13 December 2023.
7. Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA Internal Medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. PMC 4358759. PMID 25621434.
8. Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, et al. (July 2009). "Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study". Archives of Internal Medicine. 169 (14): 1317–1324. doi:10.1001/archinternmed.2009.229. PMC 2933398. PMID 19636034.
9. Farzam K, Sabir S, O'Rourke MC (2024). "Antihistamines". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30844215. Retrieved 2024-11-11.
10. Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, et al. (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLOS ONE. 6 (8): e23852. Bibcode:2011PLoSO...623852K. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.
11. "Clemastine - Mechanism, Indication, Contraindications, Dosing, Adverse Effect, Interaction, Hepatic Dose | Drug Index | Pediatric Oncall". www.pediatriconcall.com. Retrieved 2024-05-23.
12. drugs.com Clemastine at drugs.com international listings Page accessed May 10, 2015
13. Jiang S, Wang X, Cao T, Kang R, Huang L (2023). "Insights on therapeutic potential of clemastine in neurological disorders". Frontiers in Molecular Neuroscience. 16: 1279985. doi:10.3389/fnmol.2023.1279985. PMC 10568021. PMID 37840769.
14. Leigh S (12 June 2023). "Can this Medication Reverse MS? Brain Biomarker Shows It Can". UCSF. Retrieved 17 April 2024.
15. Riboni-Verri G, Chen BS, McMurran CE, Halliwell GJ, Brown JW, Coles AJ, et al. (2024). "Visual outcome measures in clinical trials of remyelinating drugs". BMJ Neurology Open. 6 (1): e000560. doi:10.1136/bmjno-2023-000560. PMC 10882304. PMID 38389586.
16. Moghaddasi M, Nabovvati M, Koushki A, Soltansanjari M, Sardarinia M, Mohebi N, et al. (June 2020). "Randomized control trial of evaluation of Clemastine effects on visual evoked potential, nerve fiber layer and ganglion cell layer complex in patients with optic neuritis". Clinical Neurology and Neurosurgery. 193: 105741. doi:10.1016/j.clineuro.2020.105741. PMID 32145678.
17. Ciccone I (2 March 2024). "Clemastine Arm of TRAP-MS Trial Halted Following Increased Disability Accumulation in Progressive Multiple Sclerosis". NeurologyLive. Retrieved 17 April 2024.
18. Dotinga R (14 March 2024). "Clemastine Tied to Worsening Symptoms in Multidrug MS Trial". Medscape. Retrieved 17 April 2024.
19. Maia M (7 March 2024). "ACTRIMS 2024: An antihistamine may speed MS disease progression". Multiple Sclerosis News Today. Retrieved 17 April 2024.

External links

• NIH Medline Plus listing on Clemastine
• The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations

• 4-Chlorophenyl compounds
• CYP2D6 inhibitors
• Diphenylmethanol ethers
• H1 receptor antagonists
• Muscarinic antagonists
• Pyrrolidines