title: The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine.
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.
authors.affiliation: Department of Research and Development, BIAL 4785 S, Mamede do Coronado, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Parada
authors.forename: Patríjcio
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D000078330:Oxcarbazepine; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D014702:Veratrine / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; D018377:Neurotransmitter Agents; D015222:Sodium Channels; D002220:Carbamazepine; C416835:eslicarbazepine acetate; D014702:Veratrine; D000078330:Oxcarbazepine