Excitotoxicity is a central mechanism in the pathogenesis of different, currently incurable, neurodegenerative diseases. One treatment targeting excitotoxicity is Riluzole (Rilutek®), a drug capable of reducing glutamate release. Currently, Riluzole is available for patients with amyotrophic lateral sclerosis (ALS) to delay the progression of the disease. However, its efficacy diminishes in advanced stages of the pathology.The aim of this study has been to characterize the effect of a novel Riluzole-derived compound (VA945) as a potential neuroprotective drug, aiming at identify a more efficient pharmacological treatment. The goal was to develop a multi-target drug able to inhibit various neuronal voltage-dependent channels. By whole-cell patch-clamp technique in the voltage-clamp configuration we characterized the effect of different concentrations [5-50-100 µM] of VA945 on isolated voltage-gated Na+, K+, and Ca2+ currents expressed by SH-SY5Y-derived neurons. In particular, we analysed the effect on amplitude, V1/2 , and slope of activation and inactivation curves. We observed that focal perfusion of VA945 resulted in a reduction of maximal conductance and a shift to the left of the activation curve (for Na+, K+, and Ca2+ currents) and the inactivation curve (for Na+ current). These results suggest a potential multi-target action of VA945 in modulating neuronal excitability, paving the way to further ex-vivo investigations on brain slices and/or in-vivo studies.