[The effect of ionotropic glutamate receptor antagonist on pentylenetetrazole-indused seizures in Krushinsky-Molodkina rats].

Krushinsky-Molodkina (KM) rats exhibit inherited susceptibility to audiogenic seizures and auditory stimuli induce generalized tonic-clonic seizures that resemble human epilepsy. The aim of this study was to compare the neurological manifestations of pentylenetetrazole (PTZ)-induced seizures in Wistar and KM rats to clarify the contribution of inherited susceptibility to audiogenic seizures, and to assess the anticonvulsant activity of NMDA receptor blockers memantine and IEM-1921 (1-phenylcyclohexylamine) in the PTZ-induced seizure model in KM rats. KM rats exhibited increased seizure severity relative to Wistar rats, and the death of KM rats was observed in 2.1 times more likely. Both NMDA receptor blockers showed anticonvulsant activity in the PTZ-induced seizure model, however IEM-1921 was more potent than memantine. IEM-1921 reduced the average intensity of the seizures by 2 points on a 5-point scale, and the total duration of generalized seizures was decreased by 41 times. IEM-1921 completely prevented the death of animals, while memantine only slightly decreased the mortality (68% in control conditions vs. 50% with administration of memantine). The results of the present study suggest that NMDA receptors are involved in the molecular mechanisms of seizures of different etiologies.