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The effects of lacosamide (LCS, Vimpat^®), an anti-convulsant and analgesic, on voltage-gated Na⁺ current (<i>I</i>_Na) were investigated. LCS suppressed both the peak (transient, <i>I</i>_Na(T)) and sustained (late, <i>I</i>_Na(L)) components of <i>I</i>_Na with the IC₅₀ values of 78 and 34 μM found in GH₃ cells and of 112 and 26 μM in Neuro-2a cells, respectively. In GH3 cells, the voltage-dependent hysteresis of persistent <i>I</i>_Na (<i>I</i>_Na(P)) during the triangular ramp pulse was strikingly attenuated, and the decaying time constant (τ) of <i>I</i>_Na(T) or <i>I</i>_Na(L) during a train of depolarizing pulses was further shortened by LCS. The recovery time course from the <i>I</i>_Na block elicited by the preceding conditioning train can be fitted by two exponential processes, while the single exponential increase in current recovery without a conditioning train was adequately fitted. The fast and slow τ’s of recovery from the <i>I</i>_Na block by the same conditioning protocol arose in the presence of LCS. In Neuro-2a cells, the strength of the instantaneous window <i>I</i>_Na (<i>I</i>_Na(W)) during the rapid ramp pulse was reduced by LCS. This reduction could be reversed by tefluthrin. Moreover, LCS accelerated the inactivation time course of <i>I</i>_Na activated by pulse train stimulation, and veratridine reversed its decrease in the decaying τ value in current inactivation. The docking results predicted the capability of LCS binding to some amino-acid residues in sodium channels owing to the occurrence of hydrophobic contact. Overall, our findings unveiled that LCS can interact with the sodium channels to alter the magnitude, gating, voltage-dependent hysteresis behavior, and use dependence of <i>I</i>_Na in excitable cells.