Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium Channel

We have studied the effects of local anesthetics QX 572, which is permanently charged, and benzocaine, which is neutral, on batrachotoxinactivated sodium channels in mouse neuroblastoma N 18 cells. The dose-response curves for each drug suggest that QX 572 and benzocaine each act on a single class of binding sites. The dissociation constants are 3.15 × 10^-5 M for QX 572 and 2.64 × 10^-4 M for benzocaine. Equilibrium and kinetic experiments indicate that both drugs are competitive inhibitors of batrachotoxin. When benzocaine and QX 572 are present with batrachotoxin, they are much more effective at inhibiting Na⁺ flux than would be predicted by a one-site model. Our results indicate that QX 572 and benzocaine bind to separate sites, each of which interacts competitively with batrachotoxin.