(Biphenyl-4-yl)methylammonium chlorides: Potent anticonvulsants that modulate Na+ currents

Hyosung Lee, Ki Duk Park, Xiao Fang Yang, Erik T. Dustrude, Sarah M. Wilson, Rajesh Khanna, Harold Kohn

Research output: Contribution to journalArticlepeer-review


We 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.

Original languageEnglish (US)
Pages (from-to)5931-5939
Number of pages9
JournalJournal of Medicinal Chemistry
Issue number14
StatePublished - Jul 25 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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