TABLE 1

Voltage-dependent block of sodium currents by tocainide, proline-like derivatives, and related benzylated analogs

The columns from left to right are as follows: drug used; concentrations able to produce the half-maximal block of sodium currents (IC₅₀) with single 10-ms test pulses to −20 mV from a holding potential of either −140 or −70 mV. The IC₅₀ values have been obtained during nonlinear least squares fit of the concentration-response data to the logistic equation described under Materials and Methods. Inactivated state-block refers to the affinity constants for inactivated sodium channels (K_i) calculated from the IC₅₀ values at −140 mV (assumed as affinity for resting state, K_r) and at −70 mV (K₋₇₀) and the relative distribution of channels between resting and inactivated state at −70 mV evaluated from steady-state inactivation curves, according to the equation described under Materials and Methods. The gain of potency of the new compounds versus Toc on both resting and inactivated channels is shown as ratios between related constants values, K_{r Toc}/K_{r drug} and K_{i Toc}/K_{i drug}, respectively. The gain of potency of each compound versus inactivated state is shown as the ratio between related K_r and K_i values (K_r/K_i).