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

• Published in: Neuroscience letters Vol. 271; no. 1; pp. 57 - 60
• Main Authors: Caeser, Manfred, Evans, Martyn L, Benham, Christopher D
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 13.08.1999; Elsevier
• Subjects: Animals; Anticonvulsants; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Benzamides - pharmacology; Benzopyrans - pharmacology; Biological and medical sciences; Carbamazepine - pharmacology; Cells, Cultured; Embryo, Mammalian; Epilepsy; Hippocampus; Hippocampus - cytology; Hippocampus - physiology; Lamotrigine; Medical sciences; Membrane Potentials - drug effects; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Neuropharmacology; Patch-Clamp Techniques; Pharmacology. Drug treatments; Phenytoin - pharmacology; Rats; SB-204269; Sodium Channel Blockers; Sodium channels; Sodium Channels - physiology; sodium currents; Triazines - pharmacology; SB-204269; Sodium channels; Anticonvulsants; Epilepsy; Hippocampus; Lamotrigine; Rat; Rodentia; Central nervous system; Anticonvulsant; Ionic channel; Ionic current; In vitro; Vertebrata; Mammalia; Neuron; Sodium; Animal; Mechanism of action; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00514-5

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 EC 50 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.