The novel persistent sodium current inhibitor PRAX-562 has potent anticonvulsant activity with improved protective index relative to standard of care sodium channel blockers.

ABSTRACT:

Objective

This study investigates the effects of PRAX-562 on sodium current (I_Na ), intrinsic neuronal excitability, and protection from evoked seizures to determine whether a preferential persistent I_Na inhibitor would exhibit improved preclinical efficacy and tolerability compared to two standard voltage-gated sodium channel (Na_V ) blockers.

Methods

Inhibition of I_Na  was characterized using patch clamp analysis. The effect on intrinsic excitability was measured using evoked action potentials recorded from hippocampal CA1 pyramidal neurons in mouse brain slices. Anticonvulsant activity was evaluated using the maximal electroshock seizure (MES) model, and tolerability was assessed by measuring spontaneous locomotor activity (sLMA)

SUBMITTER: Kahlig KM 

PROVIDER: S-EPMC9304232 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature