Selective stabilization of the intermediate inactivated Na channel by the new-generation anticonvulsant rufinamide.

Na channels undergo multiple inactivated states with different kinetics, which set the refractory period of neuronal discharges, but isolating the intermediate inactivated state has been challenging. Most classical Nachannel-inhibiting anticonvulsants bind to the fast inactivated state to reduce Nacurrents and cellular excitability. These anticonvulsants have the slow binding kinetics and thus necessitate long depolarization for drug action, a "use-dependent" effect sparing most normal activities.

How Can an Na Channel Inhibitor Ameliorate Seizures in Lennox-Gastaut Syndrome?

Objective: Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na channel inhibitors are in general ineffective against the seizures in LGS. Rufinamide is a new Na channel inhibitor, but approved for the treatment of LGS.