New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use-dependent block than mexiletine. The most potent analog, (S)-3-(2,6-dimethylphenoxy)-1-phenylpropan-1-a...

BACKGROUND Myotonia and periodic paralysis caused by sodium channel mutations show variable responses to the anti-myotonic drug mexiletine. OBJECTIVE To investigate whether variability among sodium channel mutants results from differences in drug binding affinity or in channel gating. METHODS Whole-cell sodium currents (I(Na)) were recorded in tsA201 cells expressing human wild-type (WT) an...

RATIONALE Sodium channel blockers are used as gene-specific treatments in long-QT syndrome type 3, which is caused by mutations in the sodium channel gene (SCN5A). Response to treatment is influenced by biophysical properties of mutations. OBJECTIVE We sought to investigate the unexpected deleterious effect of mexiletine in a mutation combining gain-of- function and trafficking abnormalities....

AIM The purpose of this study was to investigate the effect of mexiletine on the neural function and histopathological changes after ischemic spinal cord injury in rabbits. We also compared the effect of mexiletine to that of methylprednisolone. MATERIAL AND METHODS Twenty six male New Zealand white rabbits were randomly divided into six groups. Group 1; sham operated group (n=3) underwent on...

BACKGROUND Timothy syndrome (TS) is a rare long-QT syndrome caused by CACNA1C mutations G406R in exon 8A (TS1) and G402S/G406R in exon 8 (TS2). Management of TS is a challenge and prognosis is poor. This study aimed to explore the inheritance pattern and mechanism of an INa blocker, mexiletine, to improve clinical manifestations in TS. METHODS AND RESULTS A 2-year-old Chinese girl with a typi...

The sodium channel blocker mexiletine is considered the first-line drug in myotonic syndromes, a group of muscle disorders characterized by membrane over-excitability. We previously showed that the β-adrenoceptor modulators, clenbuterol and propranolol, block voltage-gated sodium channels in a manner reminiscent to mexiletine, whereas salbutamol and nadolol do not. We now developed a pharmacolo...

The electrophysiological effects of intravenous mexiletine in a dose of 200 to 250 mg given over 5 minutes, followed by continuous infusion of 60 to 90 mg per hour, were studied in 5 patients with normal conduction and in 20 patients with a variety of disturbances of impulse formation and conduction, by means of His bundle electrography, atrial pacing, and the extrastimulus method. In all but 2...