FELBAMATE DISPLAYS IN-VITRO ANTIEPILEPTIC EFFECTS AS A BROAD-SPECTRUMEXCITATORY AMINO-ACID RECEPTOR ANTAGONIST

The in vitro antiepileptic activity of the novel anticonvulsant drug f elbamate was tested in rat hippocampal slices on the CA1 epileptiform bursting induced by different chemical epileptogenic agents. The effec ts of felbamate were compared with those of the anticonvulsant drugs d iphenylhydantoin 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-n itroquinoxaline-2,3-dione (CNQX), felbamate at a minimum effective con centration of 1 mM induced a significant (P < 0.01) reduction of the d uration of the CA1 epileptiform bursting due to the K+ channel blocker , 4-aminopyridine, and the excitatory amino acids, kainate and quisqua late. Like the NMDA receptor antagonist ketamine, felbamate (1.6 mM) s ignificantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg2+-free' solutions. Conversely, felbamate (1.6 mM), CNQX (100 mu M) and ketamine (100 mu M) failed to affect the epil eptiform bursting induced by the GABA antagonist penicillin. Pentobarb itone (100 mu M) significantly (P < 0.01) decreased the duration of th e CA1 epileptiform bursting caused by 'Mg2+-free' solutions, 4-aminopy ridine or penicillin, while diphenylhydantoin (up to concentrations of 100 mu M) failed to have an effect. The results indicate that felbama te displays a unique profile of in vitro antiepileptic effects as a br oad spectrum antagonist of excitatory amino acid transmission.