Lack of effect of the novel anticonvulsant SB-204269 on voltage-dependent currents in neurones cultured from rat hippocampus.
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.
Caeser
M
M
Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Evans
M L
ML
Benham
C D
CD
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D000077213:Lamotrigine; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D001549:Benzamides; D001578:Benzopyrans; C102319:SB 204269; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014227:Triazines; D002220:Carbamazepine; D010672:Phenytoin; D000077213:Lamotrigine