ArticleAnnals of neurology2015
Sodium channel slow inactivation as a therapeutic target for myotonia congenita.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02251457 (Open Label Trial of Ranolazine in Myotonia Congenita, Paramyotonia Congenita, & Myotonic Dystrophy Type 1), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Open Label Trial of Ranolazine in Myotonia Congenita, Paramyotonia Congenita, & Myotonic Dystrophy Type 1
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Trial
- Efficacy of sodium channel blockers in treating myotonia is independent of action potential sodium current block.The Journal of physiology · 2026Article
- Mechanisms underlying the distinct K+ dependencies of periodic paralysis.The Journal of general physiology · 2025Article
- Pharmacological therapy of non-dystrophic myotonias.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Unraveling the pharmacological and therapeutic potential of Ranolazine beyond antianginal drug use: a new insight.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Reduced KThe Journal of physiology · 2024Article
- BK channels promote action potential repolarization in skeletal muscle but contribute little to myotonia.Pflugers Archiv : European journal of physiology · 2024Article
- Preclinical study of the antimyotonic efficacy of safinamide in the myotonic mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Periodic paralysis.Handbook of clinical neurology · 2024Review
- Plateau potentials contribute to myotonia in mouse models of myotonia congenita.Experimental neurology · 2023Article
- Blockers of Skeletal Muscle NaInternational journal of molecular sciences · 2023Review
- A novel mutation of the CLCN1 gene in a cat with myotonia congenita: Diagnosis and treatment.Journal of veterinary internal medicine · 2022Article
- Open-label pilot study of ranolazine for cramps in amyotrophic lateral sclerosis.Muscle & nerve · 2022Article
- The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.The Journal of general physiology · 2022Article
- Ranolazine: An Old Drug with Emerging Potential; Lessons from Pre-Clinical and Clinical Investigations for Possible Repositioning.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Bioisosteric Modification of To042: Synthesis and Evaluation of Promising Use-Dependent Inhibitors of Voltage-Gated Sodium Channels.ChemMedChem · 2021Article
- Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy.Cells · 2021Review
- Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?Cells · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePatients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warmup phenomenon. Our goal was to identify the mechanism underlying warmup and to use this information to guide development of novel therapy.
methodsTo determine the mechanism underlying warmup, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warmup in a mouse model of myotonia congenita.
resultsChanges in action potentials suggested slow inactivation of sodium channels as an important contributor to warmup. These data suggested that enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are approved by the US Food and Drug Administration for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested that both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested that side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine's hypoexcitability side effects.
interpretationWe conclude that ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.