Pii: S0006-2952(01)00584-6

We investigated the mechanism(s) of action of two new putative antiepileptic drugs (AEDs), (S)-(-)-10-acetoxy-10,11-dihydro-5Hdibenz[b,f]azepine-5-carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-024), by comparing their effects on the release of endogenous glutamate in hippocampal synaptosomes, with those of carbamazepine (CBZ) and oxcarbazepine (OXC). The AEDs inhibited the release of glutamate evoked by 4-aminopyridine (4-AP) or veratridine in a concentrationdependent manner, being CBZ more potent than the other AEDs. Using conditions of stimulation (30 mM KCl), where Na channels are inactivated, the AEDs did not inhibit either the Ca-dependent or -independent release of glutamate. The results indicate that BIA 2-093 and BIA 2-024 have sodium channel-blocking properties, but CBZ and OXC are more potent than the new AEDs. Moreover, the present data also indicate that Ca channels coupled to the exocytotic release of glutamate and the activity of the glutamate transporter were not affected by the AEDs. © 2001 Elsevier Science Inc. All rights reserved.