QX-314

QX-314 is a positively charged, membrane-impermeable quaternary lidocaine derivative [1][2][3][4].

QX-314 is a local anesthetic. In CAl pyramidal neurons of the guinea-pig hippocampal slice, QX-314 blocked both Na+ dependent action potentials and the voltage-dependent, non-inactivating Na+ conductance [1]. In Xenopus laevis oocytes expressed TRPV1 and TRPV4 channels, QX-314 (10, 30, and 60 mM) activated TRPV1 channels, but not TRPV4 channels. QX-314 at lower concentrations (less than 1mM) potently inhibited capsaicin-evoked TRPV1 currents with IC50 value of 8.0 μM. In TRPV1-expressing tsA201 cells, QX-314 induced transient increase in cytoplasmic Ca2+ [2].
In large-diameter human DRG neurons, flagellin/QX-314 inhibited sodium currents [3].

In three standard local anesthetic animal models, QX-314 reversibly and concentration-dependently induced long-lasting local anesthesia with a slow onset [4]. Intraplantar co-application of flagellin/QX-314 inhibited mechanical allodynia after nerve injury, chemotherapy and diabetic neuropathy in a dose-dependent way. In naive and chemotherapy-treated mice, co-application of flagellin/QX-314 selectively inhibited Aβ-fiber conduction [3].

References:
[1].  Connors BW, Prince DA. Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons. J Pharmacol Exp Ther, 1982, 220(3): 476-481.
[2].  Rivera-Acevedo RE, Pless SA, Ahern CA, Schwarz SK. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro. Anesthesiology, 2011, 114(6): 1425-1434.
[3].  Xu ZZ, Kim YH, Bang S, et al. Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade. Nat Med, 2015, 21(11): 1326-1331.
[4].  Lim TK, Macleod BA, Ries CR, et al. The quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia in animal models in vivo. Anesthesiology, 2007, 107(2): 305-311.