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Interaction of the Novel Anticonvulsant, BIA 2-093, With Voltage-Gated Sodium Channels: Comparison With Carbamazepine

Interaction of the Novel Anticonvulsant, BIA 2-093, With Voltage-Gated Sodium Channels: Comparison With Carbamazepine

M J Bonifácio, R D Sheridan, A Parada, R A Cunha, L Patmore, P Soares-da-Silva

Epilepsia. 2001 May;42(5):600-8.

PMID: 11380566

Abstract:

Purpose:
BIA 2-093 [(S)-(-)-10-acetoxy-10,11-dihydro-5H-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 [3H]-batrachotoxinin A 20-alpha-benzoate ([3H]-BTX), and [3H]-saxitoxin to define their relative potency to bind to rat brain sodium channels, and inhibition of uptake of 22Na 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 microM) 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 microM; p > 0.05) and inhibiting the uptake of 22Na (IC50 values, 36 vs. 138 microM; p > 0.05). Both drugs failed to displace [3H]-saxitoxin in concentrations up to 300 microM.
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP236395145	BIA 2-093		236395-14-5	Price

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