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Myotonia induced with clofibrate in rats

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Summary

Myotonia was induced in rats with clofibrate given in daily subcutaneous injections of 0.4 g/kg. The first myotonic discharges were recorded electromyographically from the extensor digitorum longus, tibialis anterior, and gastrocnemius muscles after 4 days on clofibrate, but from the soleus not until after 11 days. Clofibrate induced myotonic activity in chronically denervated muscle also. During repetitive nerve stimulation the electrical response of the muscle was declining in all myotonic rats. It did so also when repetitive stimulation was applied directly to the muscle, which would seem to suggest a myotonic defect as the cause. Several drugs were tested and diphenylhydantoin proved to inhibit myotonia most effectively. Animals on an extended clofibrate schedule (12 weeks) had ECG abnormalities resembling those seen in patients with myotonic dystrophy.

Zusammenfassung

Myotonie wurde in Ratten durch Verabreichung von Clofibrat in täglichen subkutanen Injektionsdosen von 0,4g/kg erzeugt. Die ersten Entladungen wurden elektromyographisch in den Extensor-digitorumlongus-, Tibialis-anterior- und Gastrocnemius-Muskeln 4 Tage nach Beginn der Clofibrat-Verabreichung registriert. Im Soleus erschienen ähnliche Entladungen erst nach 11 Tagen. Die mit Clofibrat induzierte myotonische Tätigkeit entsteht auch in einem chronisch denervierten Muskel. Eine zunehmende Verringerung der elektrischen Antwort des Muskels (MAP) im Verlauf repetitiver Reizung wurde in allen Ratten mit Myotonie festgestellt. Eine ähnliche Verringerung der Muskel-Antwortamplitude tritt im Verlauf direkter repetitiver Stimulation ein, was auf einen myotonischen Defekt als Ursache hinweisen mag. Unter mehreren untersuchten Arzneimitteln wies Diphenylhydantoin die wirksamsten antimyotonischen Eigenschaften auf. Ratten, denen Clofibrat länger verabreicht wurde (12 Wochen), wiesen EKG-Störungen auf, die denjenigen der Dystrophia-myotonica-Kranken ähnlich waren.

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Authors and Affiliations

  1. Department of Neurology, Medical Academy, ul. Oczki 6, 02-007, Warsaw, Poland

    Hubert Kwieciński

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  1. Hubert Kwieciński
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Additional information

This study was done under the agreement with NIH. Bethesda, Md., U.S.A., No. 05-002-N and was supported by a grant from the Muscular Dystrophy Association of America

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Kwieciński, H. Myotonia induced with clofibrate in rats. J. Neurol. 219, 107–116 (1978). https://doi.org/10.1007/BF00314393

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