| Identification | More | [Name]
Stugeron | [CAS]
298-57-7 | [Synonyms]
1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine
1-TRANS-CINNAMYL-4-DIPHENYLMETHYLPIPERAZINE
CINNARIZINE
(E)-1-(DIPHENYLMETHYL)-4-(3-PHENYL PROP-2-ENYL) PIPERAZINE
LABOTEST-BB LT00134701
stugeron
1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazin
1-Benzhydryl-4-[(2E)-3-phenyl-2-propenyl]piperazine
1-cinnamyl-4-(diphenylmethyl)-piperazin
1-Cinnamyl-4-(diphenylmethyl)piperazine
1-cinnamyl-4-(diphenylmethyl)-Piperazine
1-Cinnamyl-4-diphenylmethylpiperazine
516 MD
516md
Aplactan
Aplexal
Apotomin
Artate
Carecin
Cerebolan | [EINECS(EC#)]
206-064-8 | [Molecular Formula]
C26H28N2 | [MDL Number]
MFCD00056037 | [Molecular Weight]
368.51 | [MOL File]
298-57-7.mol |
| Chemical Properties | Back Directory | [Appearance]
White Powder | [Melting point ]
117-120°C | [Boiling point ]
488.83°C (rough estimate) | [density ]
1.1818 (rough estimate) | [refractive index ]
1.7620 (estimate) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
Soluble in chloroform at 50mg/ml | [form ]
powder
| [pka]
pKa 7.47(H2O t=25.0 ) (Uncertain) | [color ]
white
| [Water Solubility ]
0.75g/L(temperature not stated) | [Usage]
Calcium channel blocker with antiallergic and anti-vasoconstricting activity. Antihistaminic | [Merck ]
14,2305 | [InChIKey]
DERZBLKQOCDDDZ-JLHYYAGUSA-N | [CAS DataBase Reference]
298-57-7(CAS DataBase Reference) | [NIST Chemistry Reference]
Cinnarizine(298-57-7) |
| Safety Data | Back Directory | [Hazard Codes ]
Xn | [Risk Statements ]
R20/22:Harmful by inhalation and if swallowed .
R36/37/38:Irritating to eyes, respiratory system and skin .
R42/43:May cause sensitization by inhalation and skin contact . | [Safety Statements ]
S22:Do not breathe dust .
S24/25:Avoid contact with skin and eyes .
S36:Wear suitable protective clothing .
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice . | [WGK Germany ]
2
| [RTECS ]
TL3430000
| [HS Code ]
2933.59.2100 | [Toxicity]
LD50 oral in rat: > 6500mg/kg |
| Hazard Information | Back Directory | [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. | [Brand name]
Rinomar. | [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. |
| Questions And Answer | Back Directory | [Peripheral vasodilator]
Stugeron is a piperazine calcium channel blockers, belonging to the peripheral vasodilator. It is white or white-like crystal or crystalline powder. It is odorless and almost tasteless. It is insoluble in water, soluble in boiling ethanol and easily soluble in chloroform or benzene. Stugeron has dilatation effect on the vascular smooth muscle and has antagonism effect on various kinds of vasoconstrictor substances such as serotonin, epinephrine, bradykinin and vasopressin, etc., it can ease the vasospasm. Its antispasmodic effect is stronger than papaverine with a not obvious sedative effect. This product can enables a significant increase in the cerebral blood flow and can significantly improve the cerebral circulation and coronary circulation with longer duration of action and has inhibitory effect on various kinds of vasoactive substances. It is capable of relieving vasospasm and preventing the embrittlement of the blood vessel. In the situation of not affecting heart rate and oxygen consumption, it can increase the coronary blood flow and cardiac output. Intravenous injection of this product can cause short period of blood pressure drop while oral administration has no such effect. In addition, this product also has effect on preventing embrittlement of the blood vessel as well as anti-histamine effect.
It will onset within 30 minutes after oral administration with the plasma concentration reaching peak within 3-7 hours. The effect can last for four hours with the half-life of plasma concentration being 3 to 24 hours.
Clinically Stugeron is mainly used for the treatment of peripheral vascular disease and cerebrovascular disorders such as cerebral embolism, cerebral thrombosis, cerebral arteriosclerosis and hypertension induced circulation insufficiency, cerebral hemorrhage, subarachnoid hemorrhage convalescence and sequelae of traumatic brain injury. It also has efficacy in treating the mental neuropathy and coronary sclerosis. It can also be used for treating the inner ear vertigo and nausea, vomiting and motion sickness caused by other disorders.
The main adverse reactions of Stugeron: occasionally drowsiness, rash, gastrointestinal reactions, dizziness, fever or flu, intravenous blood pressure can cause short-term decline of the blood pressure; pregnant women should take with caution; patients of intracranial hemorrhage and acute cerebral infarction should be hanged.
The above information is edited by the Chemicalbook of Dai Xiongfeng.
| [Chemical Properties]
Stugeron hydrochloride, C26H28N2 ? 2HCI, [7002-58-6], melting point 192 ℃, the solubility in water is 2mg/100ml.
| [Uses]
It is long-efficacy, multifunction vasoconstriction antagonists. It can dilate blood vessels, improve blood circulation and prevent blood vessel embrittlement. It can be used in the treatment of cerebral vascular diseases as well as has efficacy in treating cervical vertigo caused headaches, dizziness, insomnia, memory loss, paralysis, numbness, weakness and slurred speech embolism.
| [Production method]
It can be produced through: first use anhydrous piperazine and brominated diphenyl methane for preparation of benzhydryl piperazine, then condense with chlorine allyl benzene to obtain it. Diphenyl methane was heated in the light, add bromine and incubate for 1h at 130 ℃ which generates brominated diphenyl methane, C13H11Br, [776-74-9] with the melting point of 45 ℃. Add the brominated diphenyl methane drop wise into the piperazine toluene and stir for 3h at 80-90 ℃, further wash with water after cooling, then use 10% dilute hydrochloric acid for extraction; The acid layer was basified for being precipitated, filtered and dried to give benzhydryl piperazine. Dissolve it in 95% ethanol, add sodium carbonate and add drop wise of allyl benzene at about 65 ℃, after the completion of the dropping, heat and reflux for 4h, filter hot and the filtrate was left overnight for precipitate the crystalline, filter to get the crude product of Stugeron which under refinement become finished product with melting point of 117-119 ℃. In terms of diphenyl methane, the total yield is 48.2%.
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