Lu AE98134

849000-18-6

425.50

10 mM in DMSO

Membrane Transporter/Ion Channel

Lu AE98134 is a potent and selective positive modulator of NaV_1.1 channels and also activates NaV_1.6 channels.Lu AE98134 normalizes the altered firing properties of fast spiking interneurons (FSINs) in Dlx5/6^+/- mice and can be used for the research of cognitive restoring in schizophrenia^[1]. IC50 & Target: IC50: NaV1.1; NaV1.6^[1] In Vitro: Lu AE98134 (30 uM) promotes the current mediated by NaV_1.1 channel, and it activates NaV_1.1 and NaV_1.5 and to a lesser extent NaV_1.2 but has no effect on NaV_1.4, NaV_1.6 and NaV_1.7 currents in HEK cells expressing NaV_1.1, NaV_1.2, NaV_1.6, NaV_1.5, NaV_1.6 and NaV_1.7 by step-wise depolarizing voltages using the whole-cell patchclamp configuration^[1].
Lu AE98134 (30 uM) increases the excitability of FSINs by decreasing the threshold for action potentials.Intracellular depolarizing current pulses evokes repetitive firing of action potentials at frequencies, additionally, Lu AE98134 increases the excitability since each current pulse generated a higher number of spikes (163 spikes in control; and 230 spikes in Lu AE98134)^[1].
In Vivo: The fast spiking inhibitory interneurons (FSINs) from Dlx5/6^+/? animals exhibit abnormal excitability because of a more depolarized spike threshold and broader action potentials.
Lu AE98134 (30 uM) increases the excitability of FSINs neurons from normal and Dlx5/6^+/? animals by modulating several parameters characteristic for NaV_1.1 channels. The selective activation of FSINs by Lu AE98134 restores cognitive flexibility in adult Dlx5/6^+/? mice^[1].