A Comparison of the Effect of Different Drugs on a Model of Chronic Epilepsy Kindled by Electric Stimulation of the Amygdala (2007)

Objective To compare the effects of different drugs on a model of chronic!epilepsy kindled by electric stimulus of the amygdala in rats and the possible underlying mechanisms. Methods A model of chronic epilepsy kindled by stimulation of the right amygdala with constant electric current was set up successfully in the male Wistar rat.The effects of different kinds of calcium antagonists on the after discharge duration(ADD) and Racine's staging of the model kindled by electric stimulation of the amygdala were kept under observation and an auto-control of the data before and after the medication was carried out. Results The effects of different calcium antagonists on the model were different.40～80 mg·kg-1 L-type calcium antagonist nimodipine administered by gastrogavage inhibited epilepic seizures kindled by electric stimulation of the amygdala and lowered the Racine's staging(P0.01). 200 mg·kg-1 of the L-type calcium antagonist diltiazem administered by gastrogavage inhibited the ADD(P0.05) while showing no effect on Racine's staging(P0.05).100～250 mg·kg-1 of the T-type calcium antagonist ethosuximide administered by gastrogavage inhibited the ADD(P0.05)but had no effect on the epileptic seizures and Racine's staging(P0.05).10～20 mg of the T-type calcium antagonist phenytoin sodium injected hypodermically inhibited the epileptic seizures and lowered the Racine's staging(P0.01).500 mg of the T-type calcium antagonist sodium valproate administered by gastrogavage inhibited the epileptic seizures and lowered the Racine's staging(P0.05).20～60 mg·kg-1 of the non-selective calcium antagonist flunarizine administered by gastrogavage inhibited the epileptic seizures and lowered the Racine's staging(P0.01) in a dose-dependent manner. Conclusion ①L-type and T-type calcium channels may be involved in the pathogenesis of epilepsy in the present study.②Nimodipine inhibited the epileptic seizures kindled by electric stimulation of the amygdala and relatively large doses of diltiazem inhibited the ADD probably by blocking the L-type calcium channel.③Ethosuximide,known to block the T-type calcium channels in the thalamic neurons,was shown to exert no inhibition on the epileptic seizures kindled by electric stimulation of the amygdala,suggesting that the epileptic seizures kindled by electric stimulation of the amygdala or even grandmal epilepsy have nothing to do with the low-threshold T-type calcium channel in the thalamus.④Both phenytoin sodium and sodium valproate inhibited the epileptic seizures kindled by electric stimulation of the amygdala in this study.The T-type calcium channel on which phenytoin sodium acted may be different from that on which ethosuximide did.These 2 drugs may also exert antiepileptic effects via other mechanisms.Sodium valproate,the drug usually used in the treatment of grandmal epilepsy or absence seizure,may be provided with calcium-channel blocking effects of both ethosuximide and phenytoin.⑤The antiepileptic effects of flunarizine may be attributed to their blocking actions on various types of calcium channels.