A glutamate receptor subtype antagonist inhibits seizures in rat hippocampal slices

Abstract

2-Methyl-4-oxo-3H-quinazoline-3-acetyl piperidine (Q5), a selective inhibitor of the fast-desensitising component of transmembrane Ca2+ ion influx to (S)-alpha-amino-3-hydroxy-5-methyliso-xazole-4-propionate ((S)-AMPA) was tested for possible anticonvulsant effects in the low-[Mg2+] model of experimental epilepsy. Evolutionary analysis of burst parameters such as half-width, decay time constant, burst multiplicity, instantaneous frequency and amplitude disclosed an approximate doubling of half-width within periods of interictal activity, being predictive for the onset of seizure-like events (SLEs). We found that SLEs observed in the CA3 region of rat hippocampal slices were suppressed by the application of 50 microM Q5. These results suggest an AMPA receptor function shaping the dynamics of spontaneous epileptiform activity.