IEM-1925, a Glutamate Receptor Channel Blocker, Increases the Latent Period and Decreases the Duration of Status Epilepticus in Rats in a Lithium-Pilocarpine Model of Epilepsy

摘要

Chronic experiments on male Wistar and Krushinskii–Molodkina rats, the latter having an inherited predisposition for audiogenic convulsions, addressed the effects of glutamate receptor antagonist IEM-1925 – which acts on both NMDA and Ca2+-permeable AMPA/kainate receptors – on brain electrical activity during the development of pilocarpine-induced status epilepticus (SE). Electrograms were recorded from the caudate nucleus, hippocampus, and the somatosensory, visual, and auditory areas of the cortex. The sequence of SE phase changes identified from electrogram patterns was found not to change on exposure to this blocker. In addition, IEM-1925 weakened the behavioral motor convulsive signs of SE in rats, decreasing seizure intensity from 8 to 4 points on the Pinel and Rovner 1978 scale. Furthermore, the latent period of onset of epileptiform activity in Krushinskii–Molodnika rats after administration of pilocarpine increased by 40 on the background of IEM-1925 at a dose of 10 mg/kg (on average from 12.8 ± 1.1 to 18.0 ± 2.1 min), with an almost two-fold increase in Wistar rats (from 22.5 ± 0.2 to 43.5 ± 3.7 min). The mean durations of SE after IEM-1925 (10 mg/kg) in Krushinskii–Molodnika and Wistar rats were 4.5–5 times shorter than without blocker. The data obtained here provide evidence that combined blockade of NMDA and Ca2+-permeable AMPA/kainate glutamate receptors, although unable to prevent onset of pilocarpine-induced SE, increased the latent period of the onset of status and significantly decreased both individual phase durations and the total duration of SE.