QX 314 chloride

QX 314 chloride is a relatively membrane-impermeable lidocaine derivative that selectively blocks voltage-activated Na⁺ channels on nociceptive neurons and induces a preferential nociceptive block, presumably by permeating through the channel pore of the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1), as well as the pore of transient receptor potential cation channel, subfamily A, member 1 (TRPA1). When applied externally, QX 314 chloride alone exhibits no effect on the activity of Na⁺ channels in small sensory neurons, but when applied in the presence of the TRPV1 agonist capsaicin, QX 314 chloride blocks sodium channels and inhibits sensory neuron excitability. In addition, QX 314 chloride is also effective on motor neurons, capable of inducing a strong and long-lasting motor block.

References:

1. Stueber T, Eberhardt MJ, Hadamitzky C, et al. Quaternary Lidocaine Derivative QX-314 Activates and Permeates Human TRPV1 and TRPA1 to Produce Inhibition of Sodium Channels and Cytotoxicity. Anesthesiology, 2016, 124(5): 1153-1165.

2. Binshtok AM, Bean BP, Woolf CJ. Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature, 2007, 449(7162): 607-610.