Location of the binding sites of rat Na_v1.5 channel pore blockers through the cavity site and/or the fenestration site. The structure of the pore module of rat Na_v1.5 (left) is shown as a surface. (A and B) Free-energy surface extract from Tao and Corry (2025) from metadynamics sampling using riluzole (A) or bupivacaine (B). Drugs that bind solely from the fenestration site or cavity site are listed in black, whereas the drugs that can bind from both sides are denoted in red.