Concentrations for half-maximal tonic and use-dependent block of sodium currents by chiral analogs of mexiletine
| Compound | Tonic Block IC50 | Use-Dependent Block | |
|---|---|---|---|
| 2 Hz IC50 | 10 Hz IC50 | ||
| μM | μM | μM | |
| R(−)-Mex | 74 ± 1.7 | 35 ± 5.4 | 31.0 ± 7.6 |
| S(+)-Mex | 127 ± 2.8 | 49 ± 4.5 | 32.5 ± 6.6 |
| Substitutions on Asymmetric Carbon Atom | |||
| R(−)-Me4 | 11.1 ± 0.3 | 7.6 ± 0.6 | 3.2 ± 0.3 |
| S(+)-Me4 | 9.3 ± 0.8 | 6.7 ± 0.6 | 3.0 ± 0.4 |
| R(−)-Me5 | 25.2 ± 0.6 | 10.0 ± 0.4 | 5.7 ± 0.5 |
| S(+)-Me5 | 46.1 ± 1.1 | 15.2 ± 2.1 | 5.8 ± 0.6 |
| R(−)-Me6 | 6.9 ± 0.5 | 6.5 ± 0.4 | 2.4 ± 0.1 |
| Substitutions on Aromatic Ring | |||
| R(−)-Me3 | 497 ± 25 | 344 ± 34 | 208 ± 16 |
| S(+)-Me3 | 600 ± 61 | 386 ± 60 | 236 ± 37 |
| R(−)-Me7 | 2.2 ± 0.4 | 2.08 ± 0.3 | 1.2 ± 0.1 |
| S(+)-Me7 | 7.5 ± 0.4 | 5.7 ± 0.4 | 3.1 ± 0.2 |
| R(−)-Me8 | 7.8 ± 1.4 | 6.9 ± 0.7 | 4.1 ± 0.5 |
| S(+)-Me8 | 29.8 ± 0.6 | 27.9 ± 0.6 | 15.8 ± 0.4 |
The columns from left to right are as follows: Drug used; Concentrations able to produce the half-maximal response (IC50) in producing a tonic block (calculated during infrequent depolarizing stimulation from −100 to −20 mV) and a use-dependent block calculated by using trains of depolarizing pulses at the frequency of 2 and 10 Hz. The IC50 values have been obtained during nonlinear least squares fit of the concentration-response data to the logistic equation described in Materials and Methods.