Chemical Properties
White Solid
Originator
Tavegyl,Sandoz,France,1967
Uses
Clemastine fumarate is a selective histamine H1 receptor antagonist (Ki = 0.26 nM) that also displays high affinity for muscarinic receptors (Ki = 16 nM). It has also recently been identified as a positive allosteric modulator of P2X7 receptor signaling. Clemastine fumarate has long been used to inhibit histamine-induced bronchoconstriction in asthma and airway hyperresponsive studies.
Uses
H1 Histamine receptor antagonist. Antihistaminic.
Definition
ChEBI: The fumaric acid salt of clemastine. An antihistamine with antimuscarinic and moderate sedative properties, it is used for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin condi
ions.
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).
Therapeutic Function
Antihistaminic
General Description
Dextrorotatory clemastine, R,R-2[2[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1- methylpyrrolidine hydrogen furnarate (1:1) (Tavist), has two chiral centers, each of which has the (R) absolute configuration. A comparison of the activities of the enantiomers indicates that the asymmetric center close to the terminal side chain nitrogen is of lesser importance to antihistaminic activity.
? This member of the ethanolamine series is characterized by a long duration of action, with an activity that reaches a maximum in 5 to 7 hours and persists for 10 to 12 hours. It is well absorbed when administered orally, and it is excreted primarily in the urine. The side effects are those usually encountered with this series of antihistamines. Clemastine is closely related to chlorphenoxamine, which is used for its central cholinergic-blocking activity. Therefore, it is not surprising that clemastine has significant antimuscarinic activity.
Biological Activity
H 1 -receptor antagonist. Clinically-used antihistamine.
Biochem/physiol Actions
Clemastine fumarate is an antihistamine H1-antagonist and anticholinergic that also has antipruritic activity.
Veterinary Drugs and Treatments
Clemastine may be used for symptomatic relief of histamine1-related
allergic conditions.
