Selective antagonist of neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (IC(50)=1270 nM on Nav1.1/SCN1A, 270 nM on Nav1.2/SCN2A, 491 nM on Nav1.3/SCN3A and 232 nM on Nav1.7/SCN9A). This toxin suppress Nav1.7 current amplitude without significantly altering the activation, inactivation, and repriming kinetics. Short extreme depolarizations partially activate the toxin-bound channel, indicating voltage-dependent inhibition of this toxin. This toxin increases the deactivation of the Nav1.7 current after extreme depolarizations. The toxin-Nav1.7 complex is gradually dissociated upon prolonged strong depolarizations in a voltage-dependent manner, and the unbound toxin rebinds to Nav1.7 after a long repolarization. Moreover, analysis of chimeric channels showed that the DIIS3-S4 linker is critical for toxin binding to Nav1.7. These data are consistent with this toxin interacting with Nav1.7 site 4 and trapping the domain II voltage sensor in the closed state