Cyclizine

Chemical properties

White or almost white, crystalline powder.

Originator

Marezine,BurroughsWellcome,US,1953

The Uses of Cyclizine

Cyclizine exhibits antihistamine and anticholinergic action and is used for vomiting and diarrhea. The exact mechanism of action is not known. Synonyms of this drug are marezine and migril.

The Uses of Cyclizine

Cyclizine is an antihistamine with a sedative effect used in the treatment of nausea and vomiting associated with motion sickness.

The Uses of Cyclizine

H1 antihistamine

Background

A histamine H1 antagonist given by mouth or parenterally for the control of postoperative and drug-induced vomiting and in motion sickness. (From Martindale, The Extra Pharmacopoeia, 30th ed, p935)

Indications

For prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness, and vertigo (dizziness caused by other medical problems).

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.

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.

brand name

Marezine (GlaxoSmithKline).

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.

Pharmacokinetics

Cyclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Cyclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which cyclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects.

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.

Metabolism

Cyclizine is metabolised to its N-demethylated derivative, norcyclizine, which has little antihistaminic (H1) activity compared to Cyclizine.