کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6017825 | 1580177 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs
ترجمه فارسی عنوان
ارزیابی پیشآزمون از مسدودکننده های کانال سدیم مارکر در یک مدل موش از میتونی نشان دهنده داروهای آنتی بیوتیک امیدوار کننده است
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کلمات کلیدی
میوتونی غیر دیستروفی، مسدود کننده کانال سدیم، مکزیکالتین، مدل موش پچ گیر، بیش از حد تحریک پذیری،
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
چکیده انگلیسی
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 5Â mg/kg); flecainide and orphenadrine showed greater potency (ED50 near 1Â mg/kg); lubeluzole and riluzole were the more potent (ED50 near 0.1Â mg/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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 255, May 2014, Pages 96-102
Journal: Experimental Neurology - Volume 255, May 2014, Pages 96-102
نویسندگان
Jean-François Desaphy, Roberta Carbonara, Teresa Costanza, Diana Conte Camerino,