Premium
CK‐2127107 amplifies skeletal muscle response to nerve activation in humans
Author(s) -
Andrews Jinsy A.,
Miller Timothy M.,
Vijayakumar Vipin,
Stoltz Randall,
James Joyce K.,
Meng Lisa,
Wolff Andrew A.,
Malik Fady I.
Publication year - 2018
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26017
Subject(s) - tibialis anterior muscle , medicine , skeletal muscle , pharmacodynamics , crossover study , muscle contraction , ulnar nerve , troponin , stimulation , placebo , anesthesia , pharmacokinetics , anatomy , pathology , alternative medicine , elbow , myocardial infarction
Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK‐2127107 (CK‐107), a next‐generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK‐107 would amplify the force‐frequency response of muscle in humans. Methods: To assess the force‐frequency response, participants received single doses of CK‐107 and placebo in a randomized, double‐blind, 4‐period, crossover study. The force‐frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed. Results: CK‐107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency‐dependent manner; the largest increase in peak force was ∼60% at 10 H z . Discussion: CK‐107 appears more potent and produced larger increases in force than tirasemtiv—a first‐generation FSTA—in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57 : 729–734, 2018