Abstract
Background: The role of calcium in the process of epileptogenesis and neurotoxicity and excitotoxicity during status epilepticus is involved. In fact, epileptiform bursts are often associated with influx of calcium ion into the nerve cells and a decrease in the extracellular concentration of calcium precedes the onset of seizures. Aim: To investigate the activity of nifedipine, the dihydropyridine calcium channel blocker, diazepam, the benzodiazepine anti- convulsant of established efficacy and their combinations against rat models of MES induced tonic seizure. Method: Wister albino rats of either sex, weighing between 150-220 gm were used for maximal electroshock method. Rats were divided into 10 groups, in each group n=6 total N=60.Group 1: Control, Group 2-4:Nifedipine 2, 4 and 8 mg/kg accordingly, Group 5-7: Diazepam 1,2 and 4 mg/kg accordingly, Group 8:Nifedipine (3.3mg) + Diazepam (3mg), Group 9:Nifedipine (6.6mg) + Diazepam (3mg), Group 10: Phenytoin (25mg/kg). The Controls in the central panel was set at 120 mA current. The Start-Reset knob was switched in the reset position with time of 0.2 seconds was set. The following parameters were observed. Latent period of convulsions, duration of flexion, tonic hind limb extension, posttictal sleep. Results: Nifedipine in doses of 4 and 8 mg / Kg., diazepam in all doses (1, 2 and 4 mg / Kg.) and their combinations were significantly reducing the duration of tonic hind limb extension (THLE). Only Nifedipine in doses of 2 mg / Kg. had no significant change in duration of THLE in comparison to Normal saline. The effect of Nifedipine 8 mg / Kg. on reducing the duration of THLE, indicative its anti-seizure activity on MES seizure was comparable to Diazepam in the dose of 1 mg / Kg. The MES-induced anti-seizure activity of Diazepam in doses of 1 mg / Kg. It was significantly less than Diazepam in doses of 2 and 4 mg / Kg or from the combination doses. Diazepam in 4 mg / Kg. dose was equally effective as the combination. But its effect was also equi-effective with Phenytoin. Conclusion: Nifedipine alone is inferior to diazepam in generalized tonic-clonic seizure and their combination is not having superadditive effect.
Key words: Calcium channel blockers; Diazepam; Epilepsy; Maximum electrical shock.