Table 3.

Voltage-dependent block of sodium currents by Mex and its metabolites

Drug	Voltage-dependent block		Inactivated-state block
	HP −140 mV IC50 (μM); Kr	HP −70 mV IC50 (μM); K−70	Calculated Ki (μM)
Mex	147.9±20.0	1.9±0.2	1.3
PHM	418.6±65.4	24.7±1.9	17.6
HMM	645.0±98.1a	47.0±6.4a	36.4
NHM	740.6±113.5a	25.0±3.4b	13.2

Abbreviations: HMM, hydroxy-methyl-mexiletine; HP, holding potentials; IC₅₀, half-maximal blocking concentration; K_i, affinity constant for the inactivated state; K_r, affinity constant for the resting state; Mex, mexiletine; NHM, N-hydroxy-mexiletine; NMG, N-carbonyloxy β-D-glucuronide; PHM, p-hydroxy-mexiletine.

The columns from left to right are as follows: drug used; IC₅₀ values a two different HP values: of −140 and −70 mV; inactivated-state block refers to the affinity constants for inactivated sodium channels (K_i) according to the equation in Methods.The IC₅₀ values of each metabolite were significantly different with respect to those of Mex (P<0.001).

a and b show the statistic significance by Student's t-test between the metabolites (for P<0.05 or less) as follows:

^aWith respect to PHM.

^bWith respect to HMM.