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-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
CAS Number	15686-51-8 Y
PubChem CID	26987
IUPHAR/BPS	6063
DrugBank	DB00283 Y
ChemSpider	25129 Y
UNII	95QN29S1ID
KEGG	D03535 Y
ChEBI	CHEBI:3738 Y
ChEMBL	ChEMBL1626 Y
CompTox Dashboard (EPA)	DTXSID2022832
Chemical and physical data
Formula	C21H26ClNO
Molar mass	343.90 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)[C@](OCC[C@@H]2N(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 Y Key:YNNUSGIPVFPVBX-NHCUHLMSSA-N Y
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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 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.^[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 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).^[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]