Clemastine

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Clemastine
Clemastine.svg
Clemastine ball-and-stick.png
Systematic (IUPAC) name
(2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
Clinical data
Trade names Tavist-1, Clemastine Fumurate, Tavegil, Taregyl
AHFS/Drugs.com monograph
MedlinePlus a682542
Pregnancy cat.
Legal status
  • Unscheduled;
    OTC
Routes Oral
Pharmacokinetic data
Bioavailability 39.2%
Metabolism Hepatic
Half-life 21.3 Hours
Excretion Renal
Identifiers
CAS number 15686-51-8 YesY
ATC code D04AA14 R06AA04
PubChem CID 26987
DrugBank DB00283
ChemSpider 25129 YesY
UNII 95QN29S1ID YesY
KEGG D03535 YesY
ChEBI CHEBI:3738 YesY
ChEMBL CHEMBL1626 YesY
Chemical data
Formula C21H26ClNO 
Mol. mass 343.9
 YesY (what is this?)  (verify)

Clemastine, also known as meclastin, is an antihistamine and anticholinergic. Unlike loratadine or fexofenadine, clemastine is a sedating antihistamine, however it exhibits fewer other side effects than most of the widely used antihistamines.[citation needed] Clemastine is also classified as an antipruritic (i.e. it stops itching).

Pharmacology[edit]

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 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).[1]

Clemastine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations are attained in 2-4 hours.

Mechanism of action[edit]

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.

Metabolism[edit]

Antihistamines are thought to be metabolized in the liver, mostly by mono-/didemethylation and glucuronide conjugation. It is an inhibitor of cytochrome P450 2D6 and may interfere with other drugs metabolized by this isozyme.

Indications[edit]

Clemastine is indicated for use in treating allergic rhinitis, such as sneezing, rhinorrhea, pruritus and lacrimation.

Availability[edit]

Clemastine is an OTC drug, and is available as a syrup (0.5 mg per 5mL) and tablet (1mg). It is sold in the United States and Portugal under the brand names Tavist by Novartis and as Clemastine Fumurate by Novex, Perrigo, Sandoz, Silarx, Teva and Wockhardt. In United Kingdom, Egypt, Germany, Iran, Spain and other countries sold as Tavegil, in Russia, Indonesia, Japan, Philippines, Turkey and other countries as Tavegyl and in India as Taregyl.

Brand names in other countries[edit]

Brasil - In Brasil it is sold under the brand name of Agasten by Novartis.

China - In China it is sold under the brand names Langjing (by Simcere), Si Nuo Ping (Linuo Kefeng Pharmaceutical), Tai Wei (Nutricia)

Germany - In Germany sold under the brand name Tavegil by Novartis Consumer Health.

In India, Indonesia, Turkey and United Kingdom is a sold under the brand name Taregyl by Novartis

Sweden - In Sweden it is sold under the brand name of Tavegyl and unlike the newer non-sedative antihistamines used for allergy, prescription only. By Novartis.

Toxicity[edit]

Overdosage symptoms are paradoxical, ranging from CNS depression to stimulation. Stimulation is most common in children, and is usually followed by excitement, hallucinations, ataxia, incoordination, 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.

The oral LD50 of clemastine in the rat and mouse is 3550 mg/kg and 730 mg/kg, respectively.

References[edit]

  1. ^ 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 (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLoS ONE 6 (8): e23852. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365. 

External links[edit]