Originator
Stugeron,Janssen,UK,1961
Definition
ChEBI: Cinnarizine is a N-alkylpiperazine, a diarylmethane and an olefinic compound. It has a role as an antiemetic, a histamine antagonist, a calcium channel blocker, a muscarinic antagonist, an anti-allergic agent, a H1-receptor antagonist and a geroprotector.
Manufacturing Process
This compound can be prepared by the reaction of cinnamoyl chloride with
benzhydryl piperazine. The reaction is carried out in dry benzene under reflux.
The benzene is then evaporated, the residue taken up in chloroform, washed
with dilute HCl and then made alkaline.
The chloroform layer is washed with a dilute aqueous sodium hydroxide
solution, thereafter with water, and is finally dried over potassium carbonate.
The residue, which is obtained after evaporation of the chloroform, is
dissolved by heating in a mixture of 25% of toluene and 75% of heptane. On
cooling this solution to about 20°C the product precipitates. That compound is
reduced with LiAlH4, to give cinnarizine.
Therapeutic Function
Antihistaminic
World Health Organization (WHO)
Cinnarizine, an antihistaminic and vasodilator agent, was
introduced into medicine in 1962. It is indicated for the treatment of labyrinthine
disturbances and vascular disorders, although its effectiveness in the latter
indication has not been convincingly demonstrated.
General Description
Cinnarizine is a piperazine derivative, which is extracted from wood reed roots. It exhibits antihistaminic and calcium antagonist property. Cinnarizine is used to treat vertigo, unsteadiness and cognitive disorders. Cinnarizine has anticholinergic, antiserotonergic and antidopaminergic effects. It enhances cerebral blood flow. Cinnarizine blocks the contraction of smooth muscles cells and also acts as a skin whitening agent.
Biological Activity
cinnarizine is a calcium channel blocker.blockers of calcium channel are drugs disrupting the calcium movement via calcium channels, which are usually used as antihypertensive therapies to decrease blood pressure in hypertension patients.
Biochem/physiol Actions
Cinnarizine is a piperazine and a specific anti-vertigo agent. It is used to treat and prevent vertigo and motion sickness. In addition, cinnarizine is also used as an anti-histamine agent. Chronic use of this drug leads to side effects such as extrapyramidal reactions (Parkinson, tremor and akathisia) and depression.
Mechanism of action
In addition
to its antihistaminic activity, cinnarizine possesses
Ca2+ channel blocking activity. Its vasodilator
effect probably results from blocking
the Ca2+ channels in the vascular smooth muscle
cells.
Clinical Use
Vestibular disorders
Motion sickness
Synthesis
Cinnarinzine is prepared by
alkylation of 1-diphenylmethyl piperazine with
3-phenyl-2-propenyl chloride .
in vitro
previous study found that cinnarizine could inhibit the phosphorylation of both arterial myosin p-light chain and arterial actomyosin superprecipitation. moreover, the concomitant inhibition of arterial superprecipitation and phosphorylation by perhexiline and cinnarizine was found to be similar to that of w-7. such inhibitary effect was then characterized by a rightward shift in the pca superprecipitation, depressed maximum activity as well as attenuation by exogenous calmodulin [1].
in vivo
previous animal study showed that augmented effects were obtained in mes seizure model when cinnarizine was combined with sodium valproate. whereas, in ptz-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate [2].
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: possibly increased sedative effects with
opioid analgesics.
Metabolism
Cinnarizine is extensively metabolised mainly via
CYP2D6, but there is considerable inter-individual
variation in the extent of metabolism.
The elimination of metabolites occurs as follows:
one third in the urine (unchanged as metabolites and
glucuronide conjugates) and two thirds in the faeces.
References
[1] silver pj,dachiw j,ambrose jm,pinto pb. effects of the calcium antagonists perhexiline and cinnarizine on vascular and cardiac contractile protein function. j pharmacol exp ther.1985 sep;234(3):629-35.
[2] brahmane ri,wanmali vv,pathak ss,salwe kj. role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice. j pharmacol pharmacother.2010 jul;1(2):78-81.
[3] hausler r,sabani e,rohr m. effect of cinnarizine on various types of vertigo. clinical and electronystagmographic results of a double-blind study. acta otorhinolaryngol belg.1989;43(2):177-85.
