Abstract
Epilepsy is a brain disorder characterized by seizures and convulsions.Epilepsy is the most common neurological disorder affecting 50 million people worldwide. The aetiology of the disorder is complex but genetic and pharmacological evidence suggests ion channels are important in generating seizure phenotypes. In particular, voltage-gated sodium channels have been implicated in causing seizure. Many of the marketed anti-epileptic drugs (AEDs) are ion channel modulators but their molecular target and mechanism of action are often poorly characterised. The aim of this work was to characterise the sodium channel subtype selectivity of two common AEDs, carbamezapine and phenytoin.
Human NaV1.1, 1.2, 1.4, 1.5, 1.6 and 1.7 were stably expressed in recombinant cell lines. The activity of both compounds was studied at each ion channel by automated electrophysiology. IC50 were estimated from 8 point concentration-response curves.Resting and use-dependent block were recorded at ambient room temperature.
Carbamezapine was tested to a maximal concentration of 300 micromolar against all sodium channels. Carbamezapine showed the greatest activity at hNaV1.1 subtype (~100 micromolar IC50)
