Felbamate displays in vitro antiepileptic effects as a broad spectrum excitatory amino acid receptor antagonist.

Abstract

The in vitro antiepileptic activity of the novel anticonvulsant drug felbamate was tested in rat hippocampal slices on the CA1 epileptiform bursting induced by different chemical epileptogenic agents. The effects of felbamate were compared with those of the anticonvulsant drugs diphenylhydantoin and pentobarbitone and with the effects of excitatory amino acid antagonists acting at both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Like the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), felbamate at a minimum effective concentration of 1 mM induced a significant (P < 0.01) reduction of the duration of the CA1 epileptiform bursting due to the K+ channel blocker, 4-aminopyridine, and the excitatory amino acids, kainate and quisqualate. Like the NMDA receptor antagonist ketamine, felbamate (1.6 mM) significantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg(2+)-free' solutions. Conversely, felbamate (1.6 mM), CNQX (100 microM) and ketamine (100 microM) failed to affect the epileptiform bursting induced by the GABA antagonist penicillin. Pentobarbitone (100 microM) significantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg(2+)-free' solutions, 4-aminopyridine or penicillin, while diphenylhydantoin (up to concentrations of 100 microM) failed to have an effect. The results indicate that felbamate displays a unique profile of in vitro antiepileptic effects as a broad spectrum antagonist of excitatory amino acid transmission.