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

Autor: Christopher D. Benham, Martyn L. Evans, Manfred Caeser
Rok vydání: 1999
Předmět:
Zdroj: Neuroscience Letters. 271:57-60
ISSN: 0304-3940
Popis: 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.
Databáze: OpenAIRE