<i>In vitro</i> and <i>in vivo</i> properties of aminotriazines used in this study.

<p>Shown for each compound are IC50 on non-inactivated human Nav1.7, IC50 on 20%-inactivated human Nav1.7, and IC50 on 20%-inactivated rat Nav1.7, all taken with patch-clamp electrophysiology; <i>in vitro</i> plasma protein binding; the ratio of brain to plasma concentrations <i>in vivo</i>; whether the compound produced analgesic efficacy in the rat formalin model of pain; and the plasma concentration corresponding to the lowest dose that produced efficacy. IC50s on hNav1.7 were measured with manual patch-clamp electrophysiology; IC50s on rNav1.7 were measured with the PatchXpress® automated electrophysiology platform. Brain to plasma ratios were calculated from concentrations experimentally measured following the formalin test. ND = no data. Analgesic efficacy was determined by a statistically significant (p < 0.05) decrease in formalin-induced flinching for which the same dose did not produce a reduction in movement in the open field assay that obviated the formalin result. Effective [plasma] is the mean (n = 8, except n = 7 for compound E) terminal plasma concentration produced by the lowest effective dose of each compound.</p><p><i>In vitro</i> and <i>in vivo</i> properties of aminotriazines used in this study.