Lack of effect of the novel anticonvulsant SB-204269 on voltage-dependent currents in neurones cultured front rat hippocampus

The novel anticonvulsant SB-204269 inhibits epileptiform afterdischarges in duced by high K+ in rat hippocampal slices. Its effects on voltage-gated Na + currents, measured from cultured hippocampal neurones using whole cell pa tch clamp, were compared to the effects of existing anticonvulsants. SB-204 269 produced no significant tonic block of Na+ currents nor any voltage-dep endent and frequency-dependent block at doses 50 to 500 fold higher than it s anticonvulsant EC50 of 0.2 mu M. In contrast, lamotrigine, phenytoin and carbamazepine at 50 mu M, blocked Na+ currents in a voltage-dependent manne r. SB-204269 also had no effect on action potential discharges evoked by el evating external Kf. These data suggest that direct blockade of voltage-gat ed channels does not contribute to the anticonvulsant properties of SB-2042 69 and further support the hypothesis that this compound has a novel mechan ism of action. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.