ArticleExperimental neurology2014
Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs.
Article in Experimental neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Muscle velocity recovery cycles as pharmacodynamic biomarker: Effects of mexiletine in a randomized double-blind placebo-controlled cross-over study.Clinical and translational science · 2022Trial
- Trial
- Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors.bioRxiv : the preprint server for biology · 2025Article
- Pharmacological therapy of non-dystrophic myotonias.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Preclinical study of the antimyotonic efficacy of safinamide in the myotonic mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole.Nature communications · 2024Article
- Development of Riluzole Analogs with Improved Use-Dependent Inhibition of Skeletal Muscle Sodium Channels.ACS medicinal chemistry letters · 2023Article
- Blockers of Skeletal Muscle NaInternational journal of molecular sciences · 2023Review
- Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy.Cells · 2021Review
- Article
- An Advanced Automated Patch Clamp Protocol Design to Investigate Drug-Ion Channel Binding Dynamics.Frontiers in pharmacology · 2021Article
- Characterization of Compound-Specific, Concentration-Independent Biophysical Properties of Sodium Channel Inhibitor Mechanism of Action Using Automated Patch-Clamp Electrophysiology.Frontiers in pharmacology · 2021Article
- Preclinical pharmacological in vitro investigations on low chloride conductance myotonia: effects of potassium regulation.Pflugers Archiv : European journal of physiology · 2020Article
- From Riluzole to Dexpramipexole via Substituted-Benzothiazole Derivatives for Amyotrophic Lateral Sclerosis Disease Treatment: Case Studies.Molecules (Basel, Switzerland) · 2020Review
- Skeletal muscle ClC-1 chloride channels in health and diseases.Pflugers Archiv : European journal of physiology · 2020Review
- Tetrodotoxin-Sensitive Neuronal-Type NaJournal of the American Heart Association · 2020Article
- Central Role of Subthreshold Currents in Myotonia.Annals of neurology · 2020Review
- Treatment Updates for Neuromuscular Channelopathies.Current treatment options in neurology · 2020Review
- Elucidating the Contribution of Skeletal Muscle Ion Channels to Amyotrophic Lateral Sclerosis in search of new therapeutic options.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although the sodium channel blocker mexiletine is considered the first-line drug in myotonia, some patients experiment adverse effects, while others do not gain any benefit. Other antimyotonic drugs are thus needed to offer mexiletine alternatives. In the present study, we used a previously-validated rat model of myotonia congenita to compare six marketed sodium channel blockers to mexiletine. Myotonia was induced in the rat by injection of anthracen-9-carboxylic acid, a muscle chloride channel blocker. The drugs were given orally and myotonia was evaluated by measuring the time of righting reflex. The drugs were also tested on sodium currents recorded in a cell line transfected with the human skeletal muscle sodium channel hNav1.4 using patch-clamp technique. In vivo, carbamazepine and propafenone showed antimyotonic activity at doses similar to mexiletine (ED50 close to 5mg/kg); flecainide and orphenadrine showed greater potency (ED50 near 1mg/kg); lubeluzole and riluzole were the more potent (ED50 near 0.1mg/kg). The antimyotonic activity of drugs in vivo was linearly correlated with their potency in blocking hNav1.4 channels in vitro. Deviation was observed for propafenone and carbamazepine, likely due to pharmacokinetics and multiple targets. The comparison of the antimyotonic dose calculated in rats with the current clinical dose in humans strongly suggests that all the tested drugs may be used safely for the treatment of human myotonia. Considering the limits of mexiletine tolerability and the occurrence of non-responders, this study proposes an arsenal of alternative drugs, which may prove useful to increase the quality of life of individuals suffering from non-dystrophic myotonia. Further clinical trials are warranted to confirm these results.
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