Riluzole specifically blocks inactivated Na channels in myelinated nerve fibre

The effects of 0.15-250 microM riluzole, a novel psychotropic agent with anticonvulsant properties, were studied on voltage-clamped nodes of Ranvier of isolated nerve fibres of the frog. When added to the external solution, the drug rapidly and reversibly inhibited both K and Na currents with an apparent dissociation constant of 0.09 mM. The riluzole-induced decrease of these currents was not "use-dependent". At concentrations up to 100 microM, the drug had no noticeable effect on the time course of Na current inactivation nor on the shape and the position along voltage axis of the Na conductance/voltage relationship. On the other hand, it induced substantial shifts towards negative voltages of the steady-state Na inactivation/voltage curve. From these results, according to the modulated-receptor model, an apparent dissociation constant of 0.29 microM could be calculated for riluzole-induced blockage of inactivated Na channels. The recovery from Na current inactivation was also affected by the drug. It is concluded that riluzole is a highly specific blocker of inactivated Na channels, which is more than 300 times more effective on these channels than on K or resting Na channels.