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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

ABSTRACT: 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.

SUBMITTER: Hansen R

PROVIDER: S-EPMC4260123 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

Hansen Richard R Saikali Khalil G KG Chou Willis W Russell Alan J AJ Chen Michael M MM Vijayakumar Vipin V Stoltz Randall R RR Baudry Stephane S Enoka Roger M RM Morgans David J DJ Wolff Andrew A AA Malik Fady I FI

Muscle & nerve 20141201 6

<h4>Introduction</h4>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.<h4>Methods</h4>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 fo ...[more]

PMID: 24634285

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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

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