The effects of eslicarbazepine on persistent Na(+) current and the role of the Na(+) channel beta subunits.

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Doeser A, Soares-da-Silva P, Beck H, Uebachs M

The effects of eslicarbazepine on persistent Na(+) current and the role of the Na(+) channel beta subunits.

Epilepsy Res. 2014 Feb;108(2):202-11. doi: 10.1016/j.eplepsyres.2013.11.022. Epub 2013 Dec 8.

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24368131 [ View in PubMed
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Abstract

Eslicarbazepine is the major active metabolite of eslicarbazepine acetate, a once-daily antiepileptic drug approved in Europe as adjunctive therapy for refractory partial-onset seizures in adults. This study was aimed to determine the effects of eslicarbazepine on persistent Na(+) currents (INaP) and the role of beta subunits in modulating these effects. To study the role of beta subunits of the Na(+) channel we used a mouse line genetically lacking either the beta1 or beta2 subunit, encoded by the SCN1B or SCN2B gene, respectively. Whole cell patch-clamp recordings were performed on CA1 neurons in hippocampal slices under control conditions and application of 300 muM eslicarbazepine. We examined INaP in acutely isolated CA1 neurons and repetitive firing in hippocampal slices of mice lacking beta subunits and corresponding wild-type littermates. We found that eslicarbazepine caused a significant reduction of maximal INaP conductance and an efficient reduction of the firing rate in wild-type mice. We have shown previously a paradoxical increase of conductance of INaP caused by carbamazepine in mice lacking beta1 subunits in the subthreshold range, leading to a failure in affecting neuronal firing (Uebachs et al., 2010). In contrast, eslicarbazepine did not cause this paradoxical effect on INaP in SCN1B null mice. Consequently, the effects of eslicarbazepine on repetitive firing were maintained in these animals. These results indicate that eslicarbazepine exerts effects on INaP similar to those known for carbamazepine. However, in animals lacking the beta1 Na(+) channel subunit these effects are maintained. Therefore, eslicarbazepine potentially overcomes a previously described putative mechanism of resistance to established Na(+) channel acting antiepileptic drugs.

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