To040 and To042 are potent use-dependent hNav1.4 sodium channel blockers. The compounds strengthen the molecular interaction at the local anesthetic receptor. To042 is 120-fold more potent than mexiletine in vitro in myotonia-like conditions. To042 is 100-fold more potent than mexiletine in vivo in a rat model of myotonia. To042 is a promising antimyotonic drug deserving further investigation.