MK-801 prevents chemical kindling induced by pentylenetetrazol in rats

Giorgi, Osvaldo; Orlandi, M; Lecca, Daniele; Corda, Maria Giuseppa

doi:10.1016/0014-2999(91)90152-g

Cited by 64 publications

(14 citation statements)

References 8 publications

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“…It inhibits the synaptic release of glutamate by acting at sodium channels themselves. [29] PTZ acts as convulsant by increasing glutamate levels,[27] whereas lamotrigine decreases it therefore, no significant anticonvulsant effect of lamotrigine was observed in PTZ model.…”

Section: Discussionmentioning

confidence: 99%

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Experimental re-evaluation of flunarizine as add-on antiepileptic therapy

2011

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Background:Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy.Materials and Methods:Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD50 and CD99 values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100–300 mg/kg), lamotrigine (3–12 mg/kg) and flunarizine (5–20 mg/kg), and then each group of mice was injected with CD99 dose of PTZ (65mg/kg i.p.). Another group of mice received single ED50 dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal–Wallis ANOVA on Ranks test.Results:As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection.Conclusion:As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish flunarizine as add-on therapy in refractory epilepsy.

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Section: Discussionmentioning

confidence: 99%

“…The response of PTZ was considered positive when the seizure score was ≥3. [27] CD 50 (Convulsive dose; dose producing seizures in 50% mice) and CD 99 (dose producing seizures in 99% mice) values of PTZ were obtained from the dose-response study.…”

Section: Methodsmentioning

confidence: 99%

Experimental re-evaluation of flunarizine as add-on antiepileptic therapy

2011

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“…It could represent another member of the bradykinin B 2 receptor family or a splice variant. In support of this possibility, several groups have provided evidence based on pharmacological profiles for the existence of multiple subtypes of bradykinin B 2 receptors [33, 34], and sequencing and characterization studies of the human and rat bradykinin B 2 receptor show sites for possible alternative splicing [35]. …”

Section: Resultsmentioning

confidence: 99%

Evidence for a Role of Bradykinin Neurons in the Control of Gonadotropin-Releasing Hormone Secretion

et al. 1998

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The present study provides evidence of a novel neuronal pathway for the control of GnRH secretion involving bradykinin neurons. Bradykinin neurons were shown by immunohistochemistry to be densely localized in several regions of the brain including the cortex, hippocampus and supraoptic nucleus, as well as two regions critical in the control of GnRH secretion, the organum vasculosum of the lamina terminalis and arcuate nucleus. Bradykinin dose-dependently stimulated GnRH release from male and proestrous female rat hypothalami in vitro. Antagonist studies revealed that bradykinin effects are mediated by the bradykinin B₂ receptor. The effect of bradykinin on GnRH release is not mediated by the classical major transmitter, glutamate, as glutamate antagonists had no effect on bradykinin stimulation of GnRH release. Rather, bradykinin appears to act directly on the GnRH neuron as bradykinin stimulated GnRH release directly from immortalized GnRH (GT1-7) neurons in vitro, and immunoblot studies revealed that the bradykinin B₂ receptor is present in GT1-7 neurons. The bradykinin B₂ receptor was also demonstrated in the rat hypothalamus and pituitary by immunoblotting. Bradykinin-induced exocytosis of GnRH appears to involve activation of the PKC signaling pathway, as a PKC inhibitor blocked bradykinin-induced GnRH release. Finally, bradykinin neurons appear to be important mediators of steroid signals in the hypothalamus to produce the LH surge, as central administration of a B₂ antagonist, but not a B₁ antagonist, significantly attenuated the steroid-induced LH surge in the ovariectomized female rat.

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“…7 Similar result was observed with a study done in Italy who also demonstrated reduced seizures score. 17 From the above study it has been demonstrated that lercanidipine was found to increase the seizure latency following chronic PTZ administration. In addition, our test compound also decreased the development of kindling which showed the involvement of GABAA and benzodiazepine receptors.…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant effect of lercanidipine against pentylenetetrazole induced kindling in mice

Selvaraj

Kameswari²,

Gandhi

et al. 2017

Int J Basic Clin Pharmacol

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Background: Emerging evidence has demonstrated the role of high-voltage -sensitive activated dihydropyridine (L-type, CaV1.x) channels in the development of epilepsy. Based on that we hypothesized that lercanidipine, a dihydropyridine calcium channel blocker, would protect against Pentylenetetrazole (PTZ) induced kindling in mice model of epilepsy.Methods: Kindling was induced in Swiss albino mice with PTZ in subconvulsive dose (30 mg/kg i.p.) thrice a week for nine weeks and the effect was scored using ‘4 point scoring system’. Rechallenging on the 3rd and 10th day with the same dose of PTZ was carried out after the last chronic dose.Results: The data of the present study demonstrated that pretreatment with lercanidipine (½ h before PTZ, in doses of 1 and 3 mg/kg i.p. daily) alone and in combination with diazepam (2mg/kg i.p.) had decreased the incidence and severity of seizure as well as prolonged the onset of kindling in a dose-dependent manner (p <0.05). On rechallenging, lercanidipine resulted in reduction of seizure score (p <0.05) and increased the seizure latency.Conclusions: The present study suggested that lercanidipine offered neuroprotection against PTZ induced kindling in mice.

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MK-801 prevents chemical kindling induced by pentylenetetrazol in rats

Cited by 64 publications

References 8 publications

Experimental re-evaluation of flunarizine as add-on antiepileptic therapy

Experimental re-evaluation of flunarizine as add-on antiepileptic therapy

Evidence for a Role of Bradykinin Neurons in the Control of Gonadotropin-Releasing Hormone Secretion

Anticonvulsant effect of lercanidipine against pentylenetetrazole induced kindling in mice

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