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Journal Article
Research Support, Non-U.S. Gov't
The anti-convulsants lacosamide, lamotrigine, and rufinamide reduce myotonia in isolated human and rat skeletal muscle.
Muscle & Nerve 2017 July
INTRODUCTION: 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.
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.
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