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The anti‐convulsants lacosamide, lamotrigine, and rufinamide reduce myotonia in isolated human and rat skeletal muscle
Author(s) -
Skov Martin,
Paoli Frank V.,
Nielsen Ole B.,
Pedersen Thomas H.
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25452
Subject(s) - myotonia , lamotrigine , myotonia congenita , sodium channel , skeletal muscle , medicine , sodium channel blocker , lacosamide , pharmacology , channelopathy , endocrinology , chemistry , anesthesia , myotonic dystrophy , epilepsy , sodium , organic chemistry , psychiatry
In myotonia congenita, loss of ClC‐1 Cl − channel function results in skeletal muscle hyperexcitability and myotonia. Anti‐myotonic treatment has typically targeted the voltage‐gated sodium channel in skeletal muscle (Nav1.4). In this study we explored whether 3 sodium channel‐modulating anti‐epileptics can reduce myotonia in isolated rat and human muscle. Methods Dissected muscles were rendered myotonic by ClC‐1 channel inhibition. The ability of the drugs to suppress myotonia was then assessed from subclinical to maximal clinical concentrations. Drug synergy was determined using isobole plots. Results All drugs were capable of abolishing myotonia in both rat and human muscles. Lamotrigine and rufinamide completely suppressed myotonia at submaximal clinical concentrations, whereas lacosamide had to be raised above the maximal clinical concentration to suppress myotonia completely. A synergistic effect of lamotrigine and rufinamide was observed. Conclusion These findings suggest that lamotrigine and rufinamide could be considered for anti‐myotonic treatment in myotonia congenita. Muscle Nerve 56 : 136–142, 2017.