Article: Clemastine

Clemastine
Systematic (IUPAC) name
2-[2-[1-(4-chlorophenyl)-1-phenyl-ethoxy]ethyl]-1-methyl-pyrrolidine
Identifiers
CAS number	17-7-4
ATC code	R06AA04
PubChem	2781
DrugBank	APRD00875
Chemical data
Formula	C21H26NClO
Mol. weight	343.9
Pharmacokinetic data
Bioavailability	39.2%
Metabolism	Hepatic
Half life	21.3 Hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	B (USA)
Legal status	Unscheduled; OTC
Routes	Oral

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

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

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.

Metabolism

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

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

Availability

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 under the brand name Tavist.

Toxicity

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.