clemastine

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 460041264

| IUPAC_name = (2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine

| image = Clemastine.svg

| image_class = skin-invert-image

| width = 222

| image2 = Clemastine ball-and-stick.png

| image_class2 = bg-transparent

| tradename =

| Drugs.com = {{drugs.com|monograph|clemastine-fumarate}}

| MedlinePlus = a682542

| pregnancy_US = B

| legal_status = otc

| routes_of_administration = Oral

| bioavailability = 39.2%

| metabolism = Hepatic

| elimination_half-life = 21.3 hours

| excretion = Renal

| IUPHAR_ligand = 6063

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 15686-51-8

| ATC_prefix = D04

| ATC_suffix = AA14

| ATC_supplemental = {{ATC|R06|AA04}}

| PubChem = 26987

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00283

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 25129

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 95QN29S1ID

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D03535

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 3738

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1626

| C=21 | H=26 | Cl=1 | N=1 | O=1

| smiles = Clc1ccc(cc1)[C@](OCC[C@@H]2N(C)CCC2)(c3ccccc3)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = YNNUSGIPVFPVBX-NHCUHLMSSA-N

}}

Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects.{{cite web |url=https://www.drugbank.ca/drugs/DB00283 |title=Clemastine |website=DrugBank.com}} Like all first-generation antihistamines, it is sedating.{{cite web |url=https://www.pharmacytimes.com/p2p/perspectives-on-second-generation-otc-antihistamines |url-status=dead |archive-url=https://web.archive.org/web/20120501100507/http://www.pharmacytimes.com/p2p/Perspectives-on-Second-Generation-OTC-Antihistamines |archive-date=2012-05-01 |title=Perspectives on Second-Generation OTC Antihistamines |website=Pharmacy Times |date=2012-03-30}}{{cite journal | vauthors = Krouse JH | title = Allergic rhinitis--current pharmacotherapy | journal = Otolaryngologic Clinics of North America | volume = 41 | issue = 2 | pages = 347–58, vii | date = April 2008 | pmid = 18328373 | doi = 10.1016/j.otc.2007.11.014 }}

Patented in 1960, it came into medical use in 1967.{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=547 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA547 |language=en}}

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.{{cite web |url=https://medlineplus.gov/druginfo/meds/a682542.html |title=Clemastine |website=MedlinePlus}}

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.{{cite web |title=Clemastine Side Effects: Common, Severe, Long Term |url=https://www.drugs.com/sfx/clemastine-side-effects.html |website=Drugs.com |access-date=13 December 2023 |date=23 January 2023}}

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.{{cite journal | vauthors = Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB | title = Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | journal = JAMA Internal Medicine | volume = 175 | issue = 3 | pages = 401–407 | date = March 2015 | pmid = 25621434 | pmc = 4358759 | doi = 10.1001/jamainternmed.2014.7663 | author5-link = Rebecca Hubbard }}{{cite journal | vauthors = Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, Ancelin ML | title = Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study | journal = Archives of Internal Medicine | volume = 169 | issue = 14 | pages = 1317–1324 | date = July 2009 | pmid = 19636034 | pmc = 2933398 | doi = 10.1001/archinternmed.2009.229 }}

Pharmacology

Clemastine is an antihistamine with anticholinergic and sedative effects. Antihistamines competitively bind to histamine receptor sites, thus reducing the neurotransmitter's effects.{{cite book | vauthors = Farzam K, Sabir S, O'Rourke MC | chapter = Antihistamines |date=2024 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK538188/ |access-date=2024-11-11 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30844215 }} 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).{{cite journal |vauthors=Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P|title=Identification of novel functional inhibitors of acid sphingomyelinase|journal=PLOS ONE|volume=6|issue=8|pages=e23852|year=2011|doi=10.1371/journal.pone.0023852|pmid=21909365|pmc=3166082|bibcode=2011PLoSO...623852K |doi-access=free}}

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.{{Cite web |title=Clemastine - Mechanism, Indication, Contraindications, Dosing, Adverse Effect, Interaction, Hepatic Dose {{!}} Drug Index {{!}} Pediatric Oncall |url=https://www.pediatriconcall.com/drugs/clemastine/428 |access-date=2024-05-23 |website=www.pediatriconcall.com |language=en}}

Society and culture

Clemastine is an OTC drug, and is available under many names and dosage forms worldwide. Most common brand name is Tavegyl.drugs.com [https://www.drugs.com/international/clemastine.html Clemastine at drugs.com international listings] Page accessed May 10, 2015

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).{{cite journal |vauthors=Jiang S, Wang X, Cao T, Kang R, Huang L |title=Insights on therapeutic potential of clemastine in neurological disorders |journal=Frontiers in Molecular Neuroscience |volume=16 |pages=1279985 |date=2023 |pmid=37840769 |pmc=10568021 |doi=10.3389/fnmol.2023.1279985|doi-access=free }}{{cite web |last=Leigh |first=Suzanne |title=Can this Medication Reverse MS? Brain Biomarker Shows It Can |website=UCSF |date=12 June 2023 |url=https://www.ucsf.edu/news/2023/06/425566/can-medication-reverse-ms-brain-biomarker-shows-it-can |access-date=17 April 2024}} Early phase II clinical trials showed promise for promoting remyelination in patients with MS, with clemastine improving nerve conduction velocity in the optic nerve.{{cite journal |vauthors=Riboni-Verri G, Chen BS, McMurran CE, Halliwell GJ, Brown JW, Coles AJ, Cunniffe NG |title=Visual outcome measures in clinical trials of remyelinating drugs |journal=BMJ Neurology Open |volume=6 |issue=1 |pages=e000560 |date=2024 |pmid=38389586 |pmc=10882304 |doi=10.1136/bmjno-2023-000560}}{{cite journal |vauthors=Moghaddasi M, Nabovvati M, Koushki A, Soltansanjari M, Sardarinia M, Mohebi N, Rabani S |title=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 |journal=Clinical Neurology and Neurosurgery |volume=193 |pages=105741 |date=June 2020 |pmid=32145678 |doi=10.1016/j.clineuro.2020.105741 }} 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.{{cite web |last=Ciccone |first=Isabella |title=Clemastine Arm of TRAP-MS Trial Halted Following Increased Disability Accumulation in Progressive Multiple Sclerosis |website=NeurologyLive |date=2 March 2024 |url=https://www.neurologylive.com/view/clemastine-arm-trap-ms-trial-halted-following-increased-disability-accumulation-progressive-ms |access-date=17 April 2024}}{{cite web |last=Dotinga |first=Randy |title=Clemastine Tied to Worsening Symptoms in Multidrug MS Trial |website=Medscape |date=14 March 2024 |url=https://www.medscape.com/viewarticle/unexpected-finding-clemastine-fumarate-linked-worsening-2024a10004ss |access-date=17 April 2024}}{{cite web |last=Maia |first=Margarida |title=ACTRIMS 2024: An antihistamine may speed MS disease progression |website=Multiple Sclerosis News Today |date=7 March 2024 |url=https://multiplesclerosisnewstoday.com/news-posts/2024/03/07/actrims-2024-antihistamine-may-speed-ms-disease-progression/ |access-date=17 April 2024}}

References

External links

[https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682542.html NIH Medline Plus listing on Clemastine]
[https://web.archive.org/web/20070310064609/http://jcp.sagepub.com/cgi/content/abstract/36/10/911 The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations]

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Category:4-Chlorophenyl compounds

Category:CYP2D6 inhibitors

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Category:H1 receptor antagonists

Category:Muscarinic antagonists

Category:Pyrrolidines