Каналоблокаторы NMDA-рецепторов мемантин и ИЭМ‑1921 сокращают продолжительность эпилептического статуса у крыс Вистар и Крушинского–Молодкиной в литий-пилокарпиновой модели

Abstract

The effects of pretreatment with memantine (5 mg/kg) or IEM-1921 (5 mg/kg), NMDA glutamate receptor channel blockers, on the brain electrical activity during status epilepticus (SE) induced by pilocarpine was studied in Wistar rats and Krushinsky-Molodkina rats that are susceptible to audiogenic seizures. Electrograms of the hippocampus, caudate nucleus, somatosensory, visual and auditory cortexes activity were recorded with implanted electrodes. The pretreatment with NMDA receptor blockers does not change the sequence of SE phases determined by the EEG patterns. However, in case of pretreatment with an NMDA receptor blocker, the latent period of epileptiform activity was 2-fold shorter (10–15 min) in Wistar rats. In Krushinsky-Molodkina rats, the latent period of epileptiform activity was initially shorter (13 ± 2 min), and the use of blockers did not change it. Memantine pretreatment reduced the duration of SE to ½ and 1/3 of original in Wistar and Krushinsky-Molodkina rats, respectively. In the case of IEM-1921 pretreatment, the SE duration was 7-fold shorter. NMDA receptor blockers also significantly weakened behavioral motor convulsions, reducing the seizure intensity from 8 to 4 score by the Pinel and Rovner scale [1978]. The data obtained indicate that the blockade of NMDA receptors does not prevent the typical development of pilocarpine-induced SE, however, it significantly reduces SE duration.