Marezine,BurroughsWellcome,US,1953
Cyclizine is an antihistamine with a sedative effect used in the treatment of nausea and vomiting associated with motion sickness.
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.
Nausea and vomiting
Vertigo
Motion sickness
Labyrinthine disorders
Cyclizine is metabolised in the liver to the relatively
inactive N-demethylated metabolite, norcyclizine. Both
cyclizine and norcyclizine have plasma elimination halflives of 20 hours.
Less than 1% of the total oral dose is eliminated in the
urine in 24 hours.
