Relutrigine

Relutrigine (PRAX-562) is an orally active inhibitor of persistent sodium channel. Relutrigine potently and preferentially inhibits persistent INa induced by ATX-II (Nav 1.5 activator) or the SCN8A mutation N1768D with IC50 values of 141 nM and 75 nM, respectively. Relutrigine exhibits potent use-dependent block and reduces neuronal intrinsic excitability. Relutrigine has effective anticonvulsant activity.

Relutrigine (0.001-10000 µM) has a stronger inhibitory effect on hNaV1.6 sustained sodium channel (I_Na) when compared with targeted antiepileptic drugs Carbamazepine and Lamotrigine . Relutrigine shows preference for persistent I_Na. Relutrigine (0.3 µM) significantly reduces the intrinsic excitability of wild-type CA1 pyramidal neurons^[1].

Relutrigine (0.3-40 mg/kg; po; single dose) exhibits protection in maximal electroshock seizure (MES) induced tonic hindlimb seizures, and reduces movement distance with dose-dependent manner in male CD-1 mice model^[1].

References:
[1]. Kahlig KM, et al. The novel persistent sodium current inhibitor PRAX-562 has potent anticonvulsant activity with improved protective index relative to standard of care sodium channel blockers. Epilepsia. 2022 Mar;63(3):697-708.