The Study Of Different Types Of Calcium Antagonists On Amygdala Electrically Kindling Model In Rats

Kindling seizure in rats is similar to complex partial seizures in human in terms of EEG and behavior. With its stable, long-lasting characteristics and showing no pathological damages up to now, kindling seizure in animals has been considered as one of the best models for chronic epileptics research in human being.Recently, along with the related research on calcium channels, the function of voltage-dependent calcium channel(VDCC) in epileptics gradually draws researchers' attention, and then calcium antagonists becomes an important part of antiepileptics.In this study, amygdala kindling model in rats was established and then the effects of different types of calcium antagonists and the possible mechanisms was then studied. The results are as follows:1. Amygdala kindling model in rats was established successfully.2. Nimodipine, an Ia type Calcium antagonist (Dihydropyridines, DHPs), 40⁸0mg.kg^-1 ig, dose-dependently inhibited amygdala kindled seizure in rats and reduced the Racine's stage (P<0.01).3. Diltiazem, an Ib type calcium antagonist(Benzothiazepines, BTZs), 200 mg.kg^-1 ig, inhibited inhibited amygdala kindled seizure (P<0.05) in rats while showing no effect on Racine's stage (P>0.05) .4. Verapamil, an Ic type calcium antagonist(Phenylalkylamines, PAAs), 10-40 mgkg^-1 ig, showed no effect on both amygdala kindled seizure and Racine's stage (p>0.05)5. Flunarizine, a non-selective calcium antagonist, 20⁶0 mg.kg^-1 ig, dose-dependently inhibited amygdala kindled seizure in rats and reduced the Racine's stage (P<0.01).6. Ethosuximide, a T type calcium antagonist, 100-250 mg-kg"1 ig, showed no effect on both amygdala kindled seizure and Racine's stage (P>0.05 ) .7. Phenytoin sodium, a T-type calcium antagonist, 10-20 mg-kg'1 ih , dose-dependently inhibited amygdala kindled seizure in rats and reduced the Racine's stage (PO.01).8. Sodium Valproate, a T-type calcium antagonist, 500 mg-kg"1 ig, inhibited amygdala kindled seizure in rats and reduced the Racine's stage (PO.05).As a result, the effects of different types of calcium antagonists on amygdala kindling model in rats were different. Drugs affecting L-type calcium channel, such as nimodipine and diltiazem, inhibited amygdala kindled seizure in rats, suggesting that L-type calcium channel was possibly involved in the pathogenesis of epilepsy. Verapamil showed no remarkable effect on amygdala kindled seizure, which might be due to its difficulty passing through blood-brain barrier. Phenytoin sodium and sodium valproate inhibited amygdala kindled seizure in rats, while ethosuximide, being reported to inhibit T-type calcium channel in thalamus neurons, failed to inhibit amygdala kindled seizure, suggesting that T-type calcium channel out of thalamus neurons was probably involved in generalized seizures. Flunarizine inhibited amygdala kindled seizure in rats, suggesting that it might act by a different type of calcium channel. The present study has significance in elucidating possible pathogenesis of epilepsy, in giving some suggestion on clinical administration of antiepileptics and also in developing calcium antagonists as new drugs for epileptic treatment.