Epilepsy and sodium channel blockers

Abstract

Epilepsy is one of the most frequent neurological diseases and although most patients nowadays respond well to anti-epileptic drugs (AED), 30 - 40% of them still present seizures despite treatment with 2 or more AED. This illustrates the need for discovery and testing of new molecules designed for specific brain targets. Several voltage-gated Na⁺ channel gene mutations were shown to be associated with genetic and hereditary epilepsy. Thus, while it is noteworthy that some currently available AED act through Na⁺ channels, the identified mutations in Na⁺ channel genes strongly support the development of new Na⁺ channel blockers used as AED. This review focuses on the pathophysiology of epilepsy and particularly on insight gained from the identification of mutations in idiopathic epilepsy (IE). All of the IE mutations identified concern genes coding for ion channels, suggesting a possible role of these integral membrane proteins in epileptogenesis. The recent identification of mutations in genes encoding the α1, α2 and β1 subunits of the voltage-gated Na⁺ channel (SCN1A, SCN2A, SCN1B) and their association with febrile seizures (FS) further illustrates the contribution of these channels in epilepsy. Modes of action of AED supposed to act through the voltage-gated Na⁺ channels are examined in an attempt to propose alternative routes to discover new active compounds.

• epilepsy
• sodium channel blockers