Long-term nerve excitability changes by persistent Na(+) current blocker ranolazine

The persistent Na(+) current (Na(p)) in peripheral axons plays an important functional role in controlling the axonal excitability. Abnormal Na(p) is believed to contribute to neurodegeneration and neuropathic pain, and thus it is an attractive therapeutic target. To assess the chronic behavior of selective Na(p) blockade, axonal excitability testing was performed in vivo in normal male mice exposed to ranolazine by recording the tail sensory nerve action potentials (SNAPs). Seven days after administering ranolazine i.p. (50mg/kg) daily for 1 week, nerve excitability testing showed decreased strength-duration time constant in the ranolazine group in comparison to the control (P<0.03). This change is explained by the long-term effects of ranolazine on Na(p). Importantly, ranolazine showed no effect on other ion channels that influence axonal excitability. Further study is needed to assess the chronic Na(p) blockade as a useful therapy in peripheral nerve diseases associated with abnormal nerve excitability.