The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jan 1989
Neocortical epileptogenesis in vitro: studies with N-methyl-D-aspartate, phencyclidine, sigma and dextromethorphan receptor ligands.
Slices of rat neocortex have been used to study the role of N-methyl-D-aspartate (NMDA) receptors in the induction of epileptiform activity. The NMDA antagonist potency of a range of compounds with putative anticonvulsant activity has been compared with their ability to reduce epileptiform activity in this tissue. Epileptiform activity was induced by the omission of magnesium from the bathing medium. ⋯ Sigma and dextromethorphan receptor ligands (e.g. ditolyguanidine, carbetapentane and phenytoin), whereas inactive as NMDA antagonists, reduced epileptiform activity by decreasing the number of afterpotentials per burst with less effect on the burst frequency. The quisqualate/kainate antagonist, FG9041 (6,7-dinitro-quinoxaline-2,3-dione), only reduced spontaneous bursts at doses which also reduced NMDA. Our results imply a central role for NMDA receptors in epileptogenesis in neocortical slices.