Evenamide

Abstract

In light of the persistent struggles encountered with treatment-resistant schizophrenia (TRS), the pressing urgency remains for the development and implementa- tion of novel therapeutic interventions, an essential re- quirement in the realm of health care as a notable por- tion of individuals diagnosed with schizophrenia exhibit minimal positive reactions to antipsychotic medications, even with proper treatment. Evenamide, a newly developed oral compound, selectively inhibits voltage-gated sodium channels (VGSCs) with minimal impact on over 130 other CNS targets. VGSCs are crucial for neuronal excitability and the maintenance of resting potential, playing a vital role in the creation and transmission of action potentials within neurons. Evenamide's primary action involves normalizing glutamate release induced by irregular sodium channel activity without altering baseline glutamate levels, achieved through VGSC inhibition. In animal models of psychosis, evenamide combined with other antipsychotics, including clozapine, showed beneficial outcomes, suggesting potential synergistic mechanisms. Newron’s study 014/015 revealed positive results with evenamide, showing excellent tolerability and minimal adverse effects, with 85 out of 100 patients continuing treatment for 30 weeks. The improvement in TRS symptoms was substantial and increased over time. If corroborated by forthcoming randomized and placebo-controlled trials, evenamide could potentially supplement existing antipsychotics to ameliorate symptoms in TRS cases.