Lacosamide Inhibition of Na_V1.7 Channels Depends on its Interaction With the Voltage Sensor Domain and the Channel Pore.

ABSTRACT: Lacosamide, developed as an anti-epileptic drug, has been used for the treatment of pain. Unlike typical anticonvulsants and local anesthetics which enhance fast-inactivation and bind within the pore of sodium channels, lacosamide enhances slow-inactivation of these channels, suggesting different binding mechanisms and mode of action. It has been reported that lacosamide's effect on Na_V1.5 is sensitive to a mutation in the local anesthetic binding site, and that it binds with slow kinetics to the fast-inactivated state of Na_V1.7. We recently showed that the Na_V1.7-W1538R mutation in the voltage-sensing domain 4 completely abolishes Na_V1.7 inhibition by clinically-achievable concentration of lacosamide. Our molecular docking analysis suggests a ro

SUBMITTER: Labau JIR 

PROVIDER: S-EPMC8724789 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature