Tocainide Hydrochloride

Tocainide hydrochloride is effective in the symptomatic treatment of myotonic syndromes by blocking voltage-gated sodium channels, reducing the high frequency discharges of action potentials typical of the disease. The R(-) enantiomer of tocainide at concentrations as low as 10 μM potently counteracted the abnormal excitability of myotonic goat muscle fibers by increasing the threshold current and decreasing the latency of action potential and firing capability. This concentration of R(-) tocainide almost completely abolished abnormal spontaneous electrical activity occurring in approximately 70 to 80 percent of myotonic fibers. The S(+) enantiomer was remarkably less potent, as up to 100 μM did not restore normal excitability pattern.
Tocainide blocks sodium channels in a use-dependent manner, ensuring stronger potency in situations of excessive action potential firing such as myotonia, rather than on physiological excitability. Most of the antimyotonic activity of tocainide resides in the R(-) enantiomer, suggesting that clinical use of the pure enantiomer may allow significant dose reduction and possibly fewer side effects.

Fig. 1 The effects of in vitro application of different concentrations of R(-) and S(-) tocainide enantiomers on the hyperexcitability of myotonic fibers. (Camerino D C.; et al. 2000)