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Muscle Nerve. 2014 Dec;50(6):925-31. doi: 10.1002/mus.24239.

Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

Author information

1
Research and Early Development, Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080-4808, USA.

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.

KEYWORDS:

Phase 1; fast skeletal muscle troponin activator; force-frequency relationship; skeletal muscle; tirasemtiv

PMID:
24634285
PMCID:
PMC4260123
DOI:
10.1002/mus.24239
[Indexed for MEDLINE]
Free PMC Article

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