Inhibition And Mechanisms Of MK-801 On Amygdala Kindling In Rats

MK-801 (Dizocilpine) is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor, which can easily penetrate blood-brain barrier[1] . It has been known that epileptic seizure is related to the balance between excitatory transmitters and inhibitory transmitters. We investigated the antiepileptic effects and mechanism of MK-801 on amygdala kindling in rats, which resembles complex partial epilepsy[2,3]. We investigated the antiepileptic effect and the mechanism of MK-801 on amygdala kindling in rats.Objective: To investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kindling models in rats and the effects of its combination with general antiepileptic drugs.Methods: To establish amygdala kindling models in rats and observe the effect of dizocilpine on kindling models and its combination with general antiepileptic drugs (phenobarbital, valproate and nicardipine) at ineffective dose respectively. The influence of dizocilpine on the convulsions induced by semicarbazide (SCZ) in mice were also observed.Results: Dizocilpine (0.05-0.25 mg-kg-1, ip) dose-dependently inhibited the amygdala kindled seizure, shortened the afterdischarge duration (ADD) and reduced the Racine's stage (P<0.01). The combination of dizocilpine with phenobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P<0.01). Dizocilpine (0.05-0.25 mg-kg-1, ip) significantly prolonged the latency and reduced the rate of convulsions and death in mice.Conclusion: Dizocilpine inhibits the seizure of the amygdala kindling and improve the antiepileptic activity of phenobarbital, valproate, nicardipine, which indicating that these combination may provide a new approach for treating epilepsy. The inhibition mechanism of MK-801 is related to the blockade of the voltage-operatedcalcium channels and the enhancement of the action of GABAergic system in the brain.