Figure 8.

Effects of the chiral compounds ((R)-1, (R)-4–(R)-10) and the parent compounds ((R)-2, (S)-3) on frequency (use)-dependent block of Na⁺ currents in rat embryonic cortical neurons. (A) Frequency (use)-dependence of block was examined by holding cells at the hyperpolarized potential of −80 mV and evoking currents at 10 Hz by 20 ms test pulses to −10 mV. (B) Representative overlaid traces are illustrated by pulses 1 (black) and 30 (dashed) for control (0.1% DMSO) and in the presence of (R)-10 (10 μM). (C) Summary of the maximal decrement in current amplitude observed at the end of the 30th pulse train for control or 10 μM of the indicated compounds. (R)-9 and (R)-10 caused a significant decrease in current amplitude compared with control (0.1% DMSO) (*p < 0.05, one-way ANOVA with Dunnett’s post hoc test; n = 4–6 cells per condition).