Lee, HyosungPark, Ki DukYang, Xiao-FangDustrude, Erik T.Wilson, Sarah M.Khanna, RajeshKohn, Harold2025-05-072025-05-072013Lee H, Park KD, Yang XF, et al. (Biphenyl-4-yl)methylammonium chlorides: potent anticonvulsants that modulate Na+ currents. J Med Chem. 2013;56(14):5931-5939. doi:10.1021/jm4007092https://hdl.handle.net/1805/47849We have reported that compounds containing a biaryl linked unit (Ar-X-Ar') modulated Na(+) currents by promoting slow inactivation and fast inactivation processes and by inducing frequency (use)-dependent inhibition of Na(+) currents. These electrophysiological properties have been associated with the mode of action of several antiepileptic drugs. In this study, we demonstrate that the readily accessible (biphenyl-4-yl)methylammonium chlorides (compound class B) exhibited a broad range of anticonvulsant activities in animal models, and in the maximal electroshock seizure test the activity of (3'-trifluoromethoxybiphenyl-4-yl)methylammonium chloride (8) exceeded that of phenobarbital and phenytoin upon oral administration to rats. Electrophysiological studies of 8 using mouse catecholamine A-differentiated cells and rat embryonic cortical neurons confirmed that 8 promoted slow and fast inactivation in both cell types but did not affect the frequency (use)-dependent block of Na(+) currents.en-USPublisher PolicyAmmonium compoundsAnticonvulsantsMethylaminesSodium channelsArticle