QLS-81 is a potent, selective Nav1.7 channel inhibitor with IC50 of 3.5 uM for inhibition of Nav1.7 current in whole-cell patch-clamp recording assay.
QLS-81 displays 5-fold selectivity over Nav1.4 and Nav1.5 currents.
QLS-81 is 10-fold more potent than its parent compound ralfinamide (IC50=37.1 uM).
QLS-81 (10 μM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery.
QLS-81 (10 μM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing in dissociated mouse DRG neurons.
QLS-81 (10 μM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing.
QLS-81 (2, 5, 10 mg/kg/day, i.p.) in mice for 10 days dose-dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain.