The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine.

António Parada, Patríjcio Soares-da-Silva

Index: Neurochem. Int. 40 , 435-440, (2002)

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Abstract

(S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (BIA 2-093) is endowed with high anticonvulsant activity and shares with carbamazepine (CBZ) and oxcarbazepine (OXC) the capability to inhibit voltage-gated sodium channels (VGSC). The present study was aimed to compare the effects of BIA 2-093, CBZ and OXC on the release of glutamate, aspartate, gamma-aminobutyric acid (GABA) and dopamine from striatal slices induced by the VGSC opener veratrine. The release of glutamate, aspartate, GABA and aspartate by veratrine from rat striatal slices was a concentration and time dependent process. All the three dibenzazepine carboxamide derivatives, BIA 2-093, CBZ and OXC inhibited in a concentration dependent manner (from 30 to 300 microM) the veratrine-induced release of glutamate, aspartate, GABA and dopamine. CBZ, OXC and BIA 2-093 were endowed with similar potencies in inhibiting veratrine-induced transmitter release. It is concluded that BIA 2-093, CBZ and OXC inhibit veratrine-induced transmitter release, which is in agreement with their capability to block VGSC. This property may be of importance for the anticonvulsant effects of BIA 2-093.