Clemastine

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Clemastine
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa682542
Routes of
administration		Oral
ATC code
Legal status
Legal status
Renal
Identifiers
  • (2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
JSmol)
  • Clc1ccc(cc1)[C@](OCC[C@@H]2N(C)CCC2)(c3ccccc3)C
  • 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 checkY
  • Key:YNNUSGIPVFPVBX-NHCUHLMSSA-N checkY
  (verify)

Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects.[1] Like all first-generation antihistamines, it is sedating.[2][3]

Patented in 1960, it came into medical use in 1967.[4]

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.[5]

Side effects

Overdosage symptoms are paradoxical, ranging from

pyrexia. In adults, overdose usually leads to CNS depression, ranging from drowsiness to coma.[6]

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.[7][8]

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

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).[9]

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.[medical citation needed
]

Society and culture

Clemastine is an

OTC drug, and is available under many names and dosage forms worldwide. Most common brand name is Tavegyl.[10]

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).[11][12] Early phase II clinical trials showed promise for promoting remyelination in patients with MS, with clemastine improving nerve conduction velocity in the optic nerve.[13][14] 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.[15][16][17]

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. PMID 18328373
    .
  4. ISBN 9783527607495
    .
  5. ^ "Clemastine". MedlinePlus.
  6. ^ "Clemastine Side Effects: Common, Severe, Long Term". Drugs.com. 23 January 2023. Retrieved 13 December 2023.
  7. PMID 25621434
    .
  8. PMID 19636034
    .
  9. PMID 21909365
    .
  10. ^ drugs.com Clemastine at drugs.com international listings Page accessed May 10, 2015
  11. PMID 37840769
    .
  12. ^ Leigh S (12 June 2023). "Can this Medication Reverse MS? Brain Biomarker Shows It Can". UCSF. Retrieved 17 April 2024.
  13. PMID 38389586
    .
  14. PMID 32145678
    .
  15. ^ 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.
  16. ^ Dotinga R (14 March 2024). "Clemastine Tied to Worsening Symptoms in Multidrug MS Trial". Medscape. Retrieved 17 April 2024.
  17. ^ Maia M (7 March 2024). "ACTRIMS 2024: An antihistamine may speed MS disease progression". Multiple Sclerosis News Today. Retrieved 17 April 2024.

External links