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...

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Bibliographic Details
Published in:Muscle & nerve 2014-12, Vol.50 (6), p.925-931
Main Authors: 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.
Format: Article
Language:English
Subjects:
Administration, Oral
Adolescent
Adult
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Electric Stimulation
fast skeletal muscle troponin activator
force-frequency relationship
Humans
Imidazoles - administration & dosage
Imidazoles - pharmacology
Male
Middle Aged
Muscle, Skeletal - drug effects
Muscle, Skeletal - innervation
Muscle, Skeletal - physiology
Musculoskeletal system
Neuromuscular Agents - administration & dosage
Neuromuscular Agents - pharmacology
Phase 1
Pyrazines - administration & dosage
Pyrazines - pharmacology
skeletal muscle
tirasemtiv
Troponin T - drug effects
Troponin T - physiology
Young Adult
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Summary: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 
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.24239