CLEMASTINE FUMARATE

Originator

Tavegyl,Sandoz,France,1967

Uses

Clemastine is used for allergy symptoms, rhinites, Quinke’s edema, anaphylactic shock, hay fever, allergic dermatitis and dermatosis, and chronic eczema. Synonyms of this drug are tavegil and meclastine.

Uses

Antihistaminic.

Definition

ChEBI: 2-[(2R)-1-Methylpyrrolidin-2-yl]ethanol in which the hydrogen of the hydroxy group is substituted by a 1-(4-chlorophenyl)-1-phenylethyl group (R configuration). An antihistamine with antimuscarinic and moderate sedative pr perties, it is used as its fumarate salt for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin conditions.

Manufacturing Process

9.9 g of α-methyl-p-chlorobenzhydrol are added to a suspension of 2.3 g of powdered sodamide in 30 cc of benzene. Subsequently 7.4 g of Nmethylpyrrolidyl-(2)-ethyl chloride are added and the solution is heated to the boil at reflux for 20 hours. Then shaking is first effected with water and then 4 times each time with 25 cc of 2 N hydrochloric acid. The acid extracts are made alkaline with potassium hydroxide solution while cooling strongly, and the precipitated oil is extracted with ether. After drying of the ethereal solution over potassium carbonate, the solvent is evaporated and the residue is fractionally distilled in a high vacuum, whereby N-methyl-2-[2'-(α-methyl-pchlorobenzhydryloxy)-ethyl]-pyrrolidine boils over at 154°C/0.02 mm Hg. The base is converted to the fumarate by reaction with fumaric acid.

brand name

Tavist (Novartis);Aller-ez plus;Alogynan;Antihist-1;Arrest;Benaznyl;Clemastin fumerate syrup;Corto-tavegil;Dexa-tavegil;Fumarsutin;Licasol;Maikohist;Mallermin;Rhinergal tavegil;Tavist 1;Tavist tablets;Tavist-1;Tavist-d;Tavist-syrup.

Therapeutic Function

Antihistaminic

Clinical Use

Antihistamine:
Symptomatic relief of allergy such as hay fever, urticaria

Synthesis

Clemastine, 2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine (16.1.4), is synthesized by reacting 1-(4-chlorophenyl)-1-phenylethanol (16.1.3) with 2- (2-chlorethyl)-2-methylpyrrolidine using sodium amide as a base. The starting 1-(4-chlorophenyl)-1-phenylethanol (16.1.3) is synthesized either by reacting 4-chlorobenzophenone with methylmagnesium chloride, or by reacting 4-chloroacetophenone with phenylmagnesium bromide.

Drug interactions

Potentially hazardous interactions with other drugs
Analgesics: sedative properties increased with opioid analgesics.

Metabolism

Extensively metabolised in the liver mainly by mono- and didemethylation and glucuronide conjugation. The metabolites are mainly excreted in the urine.

Raw materials

Preparation Products