The effects of mexiletine on excitability properties of human median motor axons.
OBJECTIVE
To investigate the effects of mexiletine, an analog of lidocaine, on excitability of human axons in vivo.


METHODS
Threshold tracking was used to measure multiple excitability indices (strength-duration time constant, rheobase, refractoriness, supernormality, and threshold electrotonus) in median motor axons of 20 patients with neuropathic pain or muscle cramping, before and 3 months after treatment with oral 300 mg mexiletine per day.


RESULTS
After treatment, there was a reduction in pain/muscle cramps, associated with decreased strength-duration time constants (P=0.01), increased rheobasic currents (P=0.06), and lower refractoriness (P=0.02), all of which were consistent with reduced nodal Na+ currents. Supernormality and threshold electrotonus did not change significantly. The changes in strength-duration properties suggest a decrease in persistent Na+ conductance. The lowered refractoriness after treatment might result from reduced transient Na+ currents, but the lack of change in supernormality and threshold electrotonus was not consistent with this hypothesis.


CONCLUSIONS
Oral mexiletine in a dosage of 300 mg daily suppresses persistent Na+ currents in human motor axons.


CONCLUSIONS
Measurements of the excitability indices can be used for non-invasive assessment and monitoring of the effects of mexiletine in patients with neuropathic pain or muscle cramps.
Kuwabara
Satoshi
S
Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. kuwabara-s@faculty.chiba-u.jp
Misawa
Sonoko
S
Tamura
Noriko
N
Kanai
Kazuaki
K
Hiraga
Akiyuki
A
Ogawara
Kazue
K
Nakata
Miho
M
Hattori
Takamichi
T
D000200:Action Potentials; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D001369:Axons / Q000187:drug effects*; D004056:Differential Threshold; D004334:Drug Administration Schedule; D004553:Electric Conductivity; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008801:Mexiletine / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects*; D009120:Muscle Cramp / Q000188:drug therapy / Q000503:physiopathology*; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D012032:Refractory Period, Electrophysiological; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D008801:Mexiletine