TY - JOUR
T1 - Lack of effect of the novel anticonvulsant SB 204269 on voltage dependent currents in neurones cultured from rat hippocampus
AU - Caesar, M.
AU - Evans, M.L.
AU - Benham, C.D.
N1 - Original article can be found at: http://www.sciencedirect.com/science/journal/03043940 Copyright Elsevier Ireland Ltd. DOI: 10.1016/S0304-3940(99)00514-5 [Full text of this article is not available in the UHRA]
PY - 1999
Y1 - 1999
N2 - 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 μM. In contrast, lamotrigine, phenytoin and carbamazepine at 50 μM, 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.
AB - 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 μM. In contrast, lamotrigine, phenytoin and carbamazepine at 50 μM, 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.
U2 - 10.1016/S0304-3940(99)00514-5
DO - 10.1016/S0304-3940(99)00514-5
M3 - Article
SN - 0304-3940
VL - 271
SP - 57
EP - 60
JO - Neuroscience Letters
JF - Neuroscience Letters
ER -