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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans

par Hansen, Richard;Russell, Alan A.J.;Vijayakumar, Vipin;Morgans, David D.J.;Malik, Fady F.I.;Saikali, Khalil K.G.;Chen, Michael;Chou, Willis;Wolff, Andrew A C A.A.;Stoltz, Randall R.R.;Baudry, Stéphane ;Enoka, Roger
Référence Muscle & nerve, 50, 6, page (925-931)
Publication Publié, 2014-12

Article révisé par les pairs

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Résumé :

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.