Purpose: BIA 2-093 [(S)-(-)- 10-acetoxy-10,11-dihydro-54-dibenz/b,f/azepine-5-carboxamide is endowed with an anticonvulsant potency similar to that of carbamazepine (CBZ), but produces less cognitive and motor impairment. This study evaluated whether voltage-gated sodium channels (VGSCs) are a primary locus for the action of BIA 2-093. Methods: We used the whole-cell voltage-clamp technique in the mouse neuroblastoma cell line N1E-115 to investigate the effects of BIA 2-093 and CBZ on VGSCs. displacement of [H-3]-batrachotoxinin A 20-alpha -benzoate (H-3]-BTX), and [H-3] saxitoxin to define their relative potency to bind to rat brain sodium channels, and inhibition of uptake of Na-22 by rat brain cortical synaptosomes stimulated by veratridine as a measure of sodium entry. Results: The inhibitory potencies of BIA 2-093 and CBZ increased as the holding potential was made less negative (-100. -90. -80, and -70 mV) with median inhibitory concentration (IC50) values (in muM) of, respectively, 4,337, 618, 238, and 139 for BIA 2-093, and 1,506, 594. 194, and 101 for CBZ. BIA 2-093 displayed a similar potency in displacing [3H]-BTX (IC50 values, 222 vs. 361 muM; P > 0.05) and inhibiting the uptake of Na-22 (IC50 values, 36 vs. 138 muM; p > 0.05). Both drugs failed to displace [H-3]-saxitoxin in concentrations up to 300 muM. Conclusions: BIA 2-093, like CBZ, inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the channel and interacts with neurotoxin receptor site 2, but not with receptor site 1. BIA 2-093 displayed a potency blocking VGSCs similar to that of CBZ.