Antiepileptic effects of MK-801, a noncompetitive NMDA-receptor antagonist, in the low-frequency kindling model of epilepsy.

We assessed the acute effect of MK-801 (0.05-0.7 mg/kg), a noncompetitive NMDA-receptor antagonist, on hippocampus-kindled seizures induced with low-frequency (2 Hz) electrical stimulations. MK-801 dose-dependently increased the seizure threshold (PNT, the number of stimulating pulses required for the triggering of epileptic after discharge), whereas most of the previous studies which assessed the effect of MK-801 on kindled seizures could not detect the elevation of seizure threshold by MK-801. In addition MK-801 decreased the severity of induced seizures at low doses at which previous studies could not detect the antiepileptic effect of MK-801, suggesting that the low-frequency kindling technique might be a more sensitive and reliable model of epilepsy than the conventional high-frequency kindling technique.