Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this agent has any direct effects on ion currents remains unexplored. In whole-cell current recordings, addition of Tel increased the peak amplitude of voltage-gated Na^+ (Na_V) current (I_(Na)) accompanied by the increased time constant of I_(Na) inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated I_(Na) in these cells is unlinked to either blockade of AT1R or activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). In order to explore how this compound affects the amplitude and kinetics of I_(Na) in neurons, a Hodgkin-Huxley-based (HH-based) model designed to mimic effect of Tel on the functional activities of neurons was computationally created in this study. In this framework, the parameter for h inactivation gating variable, which was changed in a stepwise fashion, was implemented to predict changes in membrane potentials (V) as a function of maximal Na^+ (G_(Na)), K^+ conductance G_K, or both. As inactivation time course of I_(Na) was increased, the bifurcation point of V versus G_(Na) became lower, and the range between subcritical and supercritical values at the bifurcation of V versus G_K correspondingly became larger. During a slowing in I_(Na) inactivation, the critical boundary between G_(Na) and G_K was shifted towards the left. Simulation studies demonstrated that progressive slowing in the inactivation time course of I_(Na) resulted in unanticipated increase of neuronal excitability by mimicking the effect of Tel in neuronal cells. Collectively, Tel can directly interact with the Na_V channel to increase peak I_(Na) as well as to slow I_(Na) inactivation. It is thus highly likely that the effects of Tel or its structurally similar drugs could be another intriguing mechanism underlying their pharmacological actions in neurons or neuroendocrine cells occurring in vivo.