Effects Of Cinnarizine Research Articles

The effects of cinnarizine on menopausal symptoms in women

Objective To evaluate the effectiveness and safety of cinnarizine in the treatment of menopausal symptoms.Design A total of 100 climacteric and symptomatic women participated in a double-blind, placebo-controlled study. They were divided into two groups of the same size: Gcin, intake of 25 mg of cinnarizine every 12 h for 6 months (n = 50); and Gpla, placebo intake every 12 hours for 6 months (n = 50). Menopausal symptoms were evaluated according to the Kupperman menopausal index on the first visit and at 6 months of treatment. A total of 62 women completed the study: 27 from the Gcin group and 35 from the Gpla group.Results Based on the Kupperman menopausal index, there were no statistically significant differences between the two groups before and after the treatment.Conclusion Our data suggest cinnarizine is not effective on menopausal symptoms because it had no more efficacy than placebo.

Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice.

Objective:To study the effect of calcium channel blockers (CCBs) cinnarizine and nifedipine on maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED).Materials and Methods:For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg), nifedipine (5 mg/kg), sodium valproate (300 mg/kg) and carbamazepine (8 mg/kg) alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher’s exact test (Ovvind Langsrud software, German version).Results:In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures.Conclusion:The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.

Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice

Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT) controls. PK-KO mice have high striatal dopamine levels and increased dopamine metabolism in spite of low reduced tyrosine hydroxylase protein. Cinnarizine, which blocks dopamine receptors and increases dopamine release, further increased dopamine metabolism. PK-KO mice increased GSH levels as a compensatory mechanism against enhanced free radical production related to acceleration of dopamine turnover. Neuronal markers, such as β-tubulin slightly increased in PK-KO and furthermore with cinnarizine. Astroglial markers were decreased in PK-KO mice, and this effect was potentiated by cinnarizine, suggesting abnormal glia in these animals. Microglia was hyperactivated in PK-KO midbrain, suggesting inflammation in these animals. Proapoptotic proteins were increased by cinnarizine and, to a lesser extent, in PK-KO mice. Our data indicate that mutation of parkin is a risk factor for drug-induced parkinsonism.

Effects of cinnarizine on different experimentally induced oedemas.

Experiments with male mice (28-32 g) of the CFLP strain showed that cinnarizine in doses of 2.5, 5.0 or 10.0 mg kg-1 significantly inhibited the extent of ear oedema induced by croton oil, capsaicin or dithranol, in a dose-dependent manner. In rats of the Wistar strain, oedema was induced in the hind paw by subplantar injection of carrageenin, and simultaneously by the application of croton oil to the inner surface of the ear. Preliminary cinnarizine treatment (5, 10 or 20 mg kg-1) inhibited the development of both types of oedema, to a statistically significant extent, in a dose-dependent manner.

Gastric and jejunal serotonin content in rats with ethanol-induced ulcers: Effects of cinnarizine and sclareol glycol

The effects of graded doses of zinc sulfate pretreatment on reserpine-induced gastric ulceration and on lysosomal fragility both in vivo and in vitro, were studied in rats. Reserpine treatment (5 mg/kg, i.p., 18 h before sacrifice)_induced marked gastric glandular ulceration and elicited the release of free β-glucuronidase from lysosomes in the gastric mucosa. A similar effect on release of this enzyme from isolated rat hepatic lysosomes was observed after in vitro incubation with reserpine. Zinc sulfate (22, 44 or 88 mg/kg, i.p., 30 h before reserpinization, or 10−3 M in vitro)_inhibited the reserpine-induced response, and zinc sulfate alone (10−11−10−3 M) also stabilized lysosomal membrane permeability to β-glucuronidase. No direct effect of zinc or reserpine on purified β-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of β-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.

Gastric histamine content and ulcer formation in rats with ethanol-induced injury. Effects of cinnarizine and flunarizine

The effects of the calcium antagonists cinnarizine and flunarizine on gastric histamine content and ulcer formation in rats with ethanol-induced injury were studied. Gastric ulcers were inflicted by oral application of 50% or 100% ethanol solution. Cinnarizine (20 mg/kg), flunarizine (10 mg/kg) and cimetidine (100 mg/kg) were administered orally 1 h before ethanol. Histamine was assayed fluorometrically. No effect of the tested drugs on 50% ethanol-induced gastric damage was observed. Cinnarizine and flunarizine inhibited 100% ethanol-induced lesion formation by 71% (p < 0.01) and 20% (p > 0.05), respectively. The inhibition exerted by cimetidine was 54% (p < 0.05). Gastric histamine content was not affected by 50% ethanol, while 100% ethanol decreased it two-fold. None of the tested drugs induced significant changes in gastric histamine levels. No correlation was obtained between the ulceroprotective effect of the used calcium antagonists and the gastric histamine content in ethanol-induced injury.

Gastric histamine content and gastric ulcer formation in cold/restraint stressed rats: Effects of cinnarizine and flunarizine

The effects of the calcium channel blockers cinnarizine (20 mg/kg p.o.) and flunarizine (10 mg/kg p.o.) on gastric and small intestine histamine content and ulcer formation were determined in cold/restraint stressed rats (4°C for 3 h). The effects of cimetidine (100 mg/kg p.o.) were studied for comparison. After the stress, a significant increase (+27%) in gastric histamine content concomitant with gastric ulceration was observed. Pretreatment with cinnarizine or flunarizine restored histamine to the control value and reduced both the incidence (−22% and −44% respectively) and the severity (-nearly 35%) of gastric ulcers. Neither marked changes in histamine content nor mucosal lesions were detected in the small intestine. The effects of cinnarizine and flunarizine resembled those of cimetidine. The obtained data suggest a possible relation between the decrease in the elevated histamine content in stressed rats and the protection against ulcer formation exerted by cinnarizine and flunarizine.

Functional, behavioral, and histological changes induced by transient global cerebral ischemia in rats: effects of cinnarizine and flunarizine.

Temporary cerebral ischemia (15 min) produced by "four-vessel occlusion" in the rat causes neurological disorders, changes in behavior (locomotor hyperactivity), and neuronal damage in the neocortex, striatum, and especially the CA1 zone of the hippocampus. We have studied the effects of two calcium overload blockers, flunarizine (50 mg/kg p.o. twice a day) and cinnarizine (100 mg/kg p.o. twice a day), on these alterations. Cinnarizine markedly improved the functional abnormalities of ischemia but had little or no effect upon the neuronal damage. In contrast, flunarizine provided far greater neuronal protection but with less obvious effects upon behavioral parameters. However, there was evidence of sedation 2 h after treating animals with this dose of flunarizine that might have masked any positive effect of the drug on behavior. We conclude that under the present experimental conditions, there is no correlation between the early and late behavioral changes observed following a temporary cerebral ischemic episode and the histological damage observed in certain vulnerable neurons, particularly in the hippocampus, 72 h after the insult.

Time-course of effects of oral cinnarizine and hyoscine on task performance

Investigations into antimotion sickness drugs fall into two main categories: efficacy ('benefits') and side-effects ('costs'). This study was of the second type. Oral cinnarizine (30 mg: normal dose; and 75 mg: 2.5 x normal dose) and placebo, were investigated using a battery of automated mental, motor, physiological and other tests in twelve young healthy male volunteers. The higher cinnarizine dose level was chosen to exaggerate effects and make it easier to track them. Oral hyoscine (1.2 mg: 2 x normal dose) was employed as a positive internal control. Side-effects were almost exclusively due to hyoscine whereas cinnarizine was almost free of significant effects even at the higher dose of 75 mg. Hyoscine impaired performance 1-3 hours postdrug, whereas the effects of cinnarizine occurred approximately 5-7 hours postdrug. This paralleled the slower time-course for the protective action of cinnarizine against motion sickness noted in earlier studies. These results, taken in conjunction with previous trials, suggest that oral cinnarizine would seem less likely than hyoscine to produce unwanted decrements in performance.

Direct inhibitory effects of some 'calcium-antagonists' and trifluoperazine on the contractile proteins in smooth muscle.

1 Taenia preparations from the guinea-pig caecum were treated with Triton X-100 and glycerol to disrupt the plasma membrane. Disruption of the sarcolemma was confirmed by electronmicroscopy. The preparations contracted in response to low concentration of Ca2+ (10-40 microM) and the contractions were dependent upon exogenous adenosine triphosphate (ATP). 2 Nifedipine (100 microM), verapamil (100 microM) and diltiazem (100 microM) did not inhibit Ca2+-induced activation of the contractile proteins. 3 In contrast, fendiline (100 microM), cinnarizine (100 microM), flunarizine (100 microM), pimozide (100 microM) and trifluoperazine (100 microM) significantly inhibited Ca2+-induced contractions. The effects of cinnarizine (100 microM) were reversible. 4 These findings disclose further differences between calcium-antagonists and suggest that certain of these agents have an intracellular site of action.

Modification of immune response by cinnarizine.

Effects of cinnarizine on immune response in mice were investigated. Mice were orally administered with cinnarizine and were immunized with sheep red blood cells (SRBC) intravenously. Numbers of plaque forming cells (PFC) to SRBC in spleen of these mice were assayed and delayed-type hypersensitivity (DTH) response to SRBC was measured. 1) PFC response in immunization with 5 X 10(6) cells/mouse of SRBC was enhanced by administration of 25 mg/kg of cinnarizine, while the response in immunization with 5 X 10(8) cells/mouse was suppressed by 25 to 200 mg/kg of cinnarizine. 2) From study on timing of administration, suppression of PFC response by 6.25 to 200 mg/kg of cinnarizine was observed at 24 hr. after the immunization. 3) 12.5 to 200 mg/kg of cinnarizine suppressed polyclonal B cell activation induced by lipopolysaccharide (LPS). 4) Colchicine induced suppressor T cell inactivation was prevented by administration of 50 mg/kg of cinnarizine and it was suggested that cinnarizine may induce suppressor T cells from the study of adoptive cell transfer system. 5) 50 mg/kg of cinnarizine showed the suppression of DTH response in expression phase, but not in induction phase. It was concluded that immune responses in mice were modified by cinnarizine.

Selective effect of cinnarizine on the vestibular nucleus neurons.

Effects of cinnarizine were studied on the lateral vestibular nucleus (LVN) and spinal trigeminal nucleus (STN) of cats anesthetized with alpha-chloralose. Cinnarizine did not produce any obvious alterations of the field potential and spike generation of type B interneurons in STN elicited by trigeminal nerve stimulation as well as the field potential in LVN by vestibular nerve stimulation. Spike generation of monosynaptic LVN neurons elicited by the suprathreshold stimulus to the vestibular nerve was unaffected by cinnarizine up to 4 mg/kg. When the subthreshold stimulus was applied to the vestibular nerve, however, the spike number of LVN monosynaptic neurons was significantly increased after cinnarizine treatment. The enhancement of spike firing by cinnarizine upon both supra- and subthreshold stimuli to the vestibular nerve was found to be more pronounced in LVN polysynaptic neurons than monosynaptic ones. Since the effect of cinnarizine on LVN neurons was not dose-dependent, it is suggested that the enhanced responsiveness of the neurons by the drug might be due to an increase of blood flow, but not to a direct excitation of the neurons themselves.