A Study of Anticonvulsant Effect of Flunarizine and Nifedipine in Comparison With Sodium Valproate on Mes and PTZ Models of Epilepsy in Albino Rats

Abstract

BACKGROUND: CA +2 ions are involved in initiation as well as spread of seizures. Hence current study was undertaken to evaluate the anticonvulsant effect of calcium channel blockers flunarizine, nifedipine and compare their efficacy with that of sodium valproate, the broad spectrum anticonvulsant in MES and PTZ induced seizures in albino rats. MATERIALS AND METHODS: Albino rats were treated with nifedipine 2.5mg/kg, 5mg/kg, flunarizine 7.5mg/kg,15mg/kg and sodium valproate 250mg/kg bodyweight intraperitoneally and the effects were observed in MES and PTZ models of epilepsy. The parameters observed in MES model was, duration of HLTE phase. Convulsive phase, and post ictal depressive phase. In PTZ model duration of seizure latency, duration of convulsion, and duration post ictal depression were observed. RESULTS: our study demonstrated that both calcium channel blockers afford protection against convulsions induced in both models, and flunarizine affords higher degree of protection than nifedipine, with its efficacy almost approaching that of sodium valproate. CONCLUSION: Flunarizine has significant, while nifedipine has moderate degree of anticonvulsant activity as compared to sodium valproate. KEYWORDS: Epilepsy, flunarizine, nifedipine, sodium valproate, MES model, PTZ model. ABBREVIATIONS: MES -maximal electro shock seizures, PTZ -pentylene tetrazole, HLTEhind limb tonic exetension, PID -post ictal depression. INTRODUCTION:Incidence of epilepsy is approximately 0.3% to 0.5% in different populations, 1 and although most epileptic seizures can be controlled by available antiepileptic drugs about 20% of them are still refractory to treatment. 2 Ca +2 ions are involved in both seizure initiation and propagation. It is the influx of extracellular ca +2 ions into the neuron through the calcium channels in the beginning that leads to the opening of the voltage gated sodium channels. Influx of Na + ions then causes generation of repetitive action potential causing seizures. 3 So if we can prevent the influx of ca +2 ions into the neuron by blocking calcium channels with the help of calcium channel blockers, the seizure activity can be prevented.Thus we took up this study wherein we evaluate and compare as well, the anticonvulsant activity of calcium channel blockers nifedipine and flunarizine 4 with sodium valproate, the broad spectrum anticonvulsant having multiple mechanisms of action, 5,6 in MES and PTZ induced seizures in albino rats.