(Biphenyl-4-yl)methylammonium Chlorides: Potent Anticonvulsants That Modulate Na+ Currents

Title
(Biphenyl-4-yl)methylammonium Chlorides: Potent Anticonvulsants That Modulate Na+ Currents
Authors
이효성박기덕Xiao-Fang YangErik T. DustrudeSarah M. WilsonRajesh KhannaHarold Kohn
Keywords
anticonvulsant; epilepsy; lacosamide; sodium channel; slow inactivation
Issue Date
2013-07
Publisher
Journal of medicinal chemistry
Citation
VOL 56, NO 14, 5931-5939
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/45205
ISSN
00222623
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KIST Publication > Article
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