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  • Title: Lack of effect of the novel anticonvulsant SB-204269 on voltage-dependent currents in neurones cultured from rat hippocampus.
    Author: Caeser M, Evans ML, Benham CD.
    Journal: Neurosci Lett; 1999 Aug 13; 271(1):57-60. PubMed ID: 10471213.
    Abstract:
    The novel anticonvulsant SB-204269 inhibits epileptiform afterdischarges induced by high K+ in rat hippocampal slices. Its effects on voltage-gated Na+ currents, measured from cultured hippocampal neurones using whole cell patch clamp, were compared to the effects of existing anticonvulsants. SB-204269 produced no significant tonic block of Na+ currents nor any voltage-dependent and frequency-dependent block at doses 50 to 500 fold higher than its anticonvulsant EC50 of 0.2 microM. In contrast, lamotrigine, phenytoin and carbamazepine at 50 microM, blocked Na+ currents in a voltage-dependent manner. SB-204269 also had no effect on action potential discharges evoked by elevating external K+. These data suggest that direct blockade of voltage-gated channels does not contribute to the anticonvulsant properties of SB-204269 and further support the hypothesis that this compound has a novel mechanism of action.
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