Chemical Properties
White or almost white, crystalline powder.
Definition
ChEBI: An N-alkylpiperazine in which one nitrogen of the piperazine ring is substituted by a methyl group, while the other is substituted by a diphenylmethyl group.
Brand name
Marezine (GlaxoSmithKline).
Originator
Marezine,BurroughsWellcome,US,1953
Preparation
Cyclizine is prepared through the alkylation of N-methylpiperazine with benzhydryl chloride.
Manufacturing Process
One-tenth mol (20 g) of benzhydryl chloride was mixed with 0.19 mol (19 g)
of N-methylpiperazine and about 10 cc of benzene and the whole was heated
on the steam bath four hours. The contents of the flask was partitioned
between ether and water, and the ethereal layer was washed with water until
the washings were neutral. The base was then extracted from the ethereal
layer by N hydrochloric acid and the extract, made acid to Congo red paper,
was evaporated under vacuum. 29.5 g of the pure dihydrochloride of Nmethyl-N'-benzhydryl piperazine was recovered from the residue by
recrystallization from 95% alcohol melting above 250°C with decomposition.
The addition of alkali to an aqueous solution of the dihydrochloride liberated
the base which was recovered by recrystallization from petroleum ether
melting at 105.5° to 107.5°C.
Therapeutic Function
Antinauseant
General Description
Cyclizine hydrochloride,1-(diphenylmethyl)-4-methylpiperazine monohydrochloride(Marezine), occurs as a light-sensitive, white crystallinepowder with a bitter taste. It is slightly soluble in water(1:115), in alcohol (1:115), and in chloroform (1:75). It isused primarily in the prophylaxis and treatment of motionsickness. The lactate salt (Cyclizine Lactate Injection,United States Pharmacopoeia [USP]) is used for intramuscular(IM) injection because of the limited water solubilityof the hydrochloride. The injection should be stored in acold place, because if it is stored at room temperature forseveral months, a slight yellow tint may develop. This doesnot indicate a loss in biologic potency.
Clinical Use
It can be used not only in the treatment
of allergic diseases, but also in the management
of postoperative, irradiation or druginduced
vomiting. Cyclizine dependence has
been suggested to occur when it is used in combination
with analgesics in long-term therapy.
For this reason, several countries have removed
cyclicine from analgesic combination preparations.
Synthesis
Cyclizine, 1-(diphenylmethyl)-4-methylpiperazine (16.1.15), is synthesized by
alkylating 1-methylpiperazine with benzhydrylbromide.
