Lu AE98134, an activator of voltage-gated sodium channels, acts as a partly selective positive modulator of Nav1.1 channels and also increases the activity of Nav1.2 and Nav1.5 channels while not affecting Nav1.4, Nav1.6, and Nav1.7 channels. Lu AE98134 can be used to analyze pathophysiological functions of the Nav1.1 channel in various central nervous system diseases, including cognitive restoring in schizophrenia, et al[1].

Lu AE98134 (30 μM) enhances Navv1.1-mediated currents and activates Nav1.5 and, to a lesser extent, Nav1.2, while it has no effect on Nav1.4, Nav1.6, or Nav1.7 currents in HEK cells expressing these channels via step-wise depolarizing voltages using whole-cell patch-clamp configuration[1]. Additionally, Lu AE98134 (30 μM) increases the excitability of FSINs by lowering the action potential threshold, inducing a higher frequency of repetitive firing and increasing the number of spikes generated per current pulse (163 spikes in control vs. 230 spikes with Lu AE98134)[1].

FSINs from Dlx5/6+/- animals exhibit abnormal excitability due to a more depolarized spike threshold and broader action potentials. Lu AE98134 (30 μM) enhances the excitability of FSINs neurons from both normal and Dlx5/6+/- animals by modulating parameters characteristic of NaV1.1 channels. Selective activation of FSINs by Lu AE98134 restores cognitive flexibility in adult Dlx5/6+/- mice [1].