替拉西泮增强人类骨骼肌对神经激活的反应。
Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.
作者信息
Hansen Richard, Saikali Khalil G, Chou Willis, Russell Alan J, Chen Michael M, Vijayakumar Vipin, Stoltz Randall R, Baudry Stephane, Enoka Roger M, Morgans David J, Wolff Andrew A, Malik Fady I
机构信息
Research and Early Development, Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080-4808, USA.
出版信息
Muscle Nerve. 2014 Dec;50(6):925-31. doi: 10.1002/mus.24239.
INTRODUCTION
In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans.
METHODS
Healthy men received tirasemtiv and placebo in a randomized, double-blind, 4-period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force-frequency relationship of tibialis anterior dorsiflexion was assessed after dosing.
RESULTS
Tirasemtiv increased force produced by the tibialis anterior in a dose-, concentration-, and frequency-dependent manner with the largest increases [up to 24.5% (SE 3.1), P < 0.0001] produced at subtetanic nerve stimulation frequencies (10 Hz).
CONCLUSIONS
The data confirm that tirasemtiv amplifies the response of skeletal muscle to nerve input in humans. This outcome provides support for further studies of tirasemtiv as a potential therapy in conditions marked by diminished neuromuscular input.
引言
在本研究中，我们检验了以下假设：替瑞西肽是一种选择性快速骨骼肌肌钙蛋白激活剂，可使肌节对钙敏感，它能够增强人体肌肉对神经肌肉输入的反应。
方法
健康男性按照随机、双盲、4期交叉设计接受替瑞西肽和安慰剂。经皮刺激腓深神经以激活胫骨前肌并引起足背屈。给药后评估胫骨前肌背屈的力-频率关系。
结果
替瑞西肽以剂量、浓度和频率依赖性方式增加胫骨前肌产生的力量，在次强直神经刺激频率（10Hz）下增加幅度最大[高达24.5%（标准误3.1），P<0.0001]。
结论
数据证实替瑞西肽可增强人体骨骼肌对神经输入的反应。这一结果为进一步研究替瑞西肽作为神经肌肉输入减少相关疾病的潜在治疗方法提供了支持。
Zotero 插件