Enhanced Anticonvulsant Efficacy and Tolerability of PRAX-562: A Comparative Study with Traditional Sodium Channel Blockers

This research aimed to explore the impact of PRAX-562 on sodium currents, neuronal excitability, and seizure protection, comparing its efficacy and safety to traditional sodium channel blockers. The study utilized patch clamp technology to assess I_Na inhibition and recorded action potentials from mouse brain slices to measure excitability effects. Anticonvulsant properties were evaluated through the MES model, while tolerability was gauged by spontaneous locomotor activity.

Results showed that PRAX-562 effectively and selectively reduced persistent I_Na, with a much higher preference for this effect compared to traditional blockers like carbamazepine. The compound also displayed a strong use-dependent block. Unlike carbamazepine, PRAX-562 decreased neuronal excitability with minimal impact on action potential amplitude. At a dosage of 10 mg/kg, PRAX-562 fully prevented seizures without affecting spontaneous locomotor activity, indicating a high protective index compared to carbamazepine and lamotrigine.

The significance of these findings suggests that PRAX-562 has strong anticonvulsant activity akin to carbamazepine but with superior tolerability, possibly due to its selective targeting of persistent I_Na. This selective targeting could offer a novel therapeutic approach for conditions characterized by hyperexcitability, where traditional sodium channel blockers have shown efficacy but limited tolerability.