Relutrigine (PRAX-562), an orally active persistent sodium channel inhibitor, potently and selectively targets persistent I Na, induced either by ATX-II (Nav 1.5 activator) or SCN8A mutation N1768D, with IC 50 values of 141 nM and 75 nM, respectively. Demonstrating a potent use-dependent block, it effectively reduces neuronal intrinsic excitability and exhibits significant anticonvulsant activity.