(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: Research - peer-reviewArticle

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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.

LanguageEnglish (US)
Pages5931-5939
Number of pages9
JournalJournal of Medicinal Chemistry
Volume56
Issue number14
DOIs
StatePublished - Jul 25 2013
Externally publishedYes

Fingerprint

Anticonvulsants
Chlorides
diphenyl
methylamine
Electroshock
Phenytoin
Phenobarbital
Catecholamines
Oral Administration
Seizures
Animal Models
Neurons
Inhibition (Psychology)

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Lee, H., Park, K. D., Yang, X. F., Dustrude, E. T., Wilson, S. M., Khanna, R., & Kohn, H. (2013). (Biphenyl-4-yl)methylammonium chlorides: Potent anticonvulsants that modulate Na+ currents. Journal of Medicinal Chemistry, 56(14), 5931-5939. DOI: 10.1021/jm4007092

(Biphenyl-4-yl)methylammonium chlorides : Potent anticonvulsants that modulate Na+ currents. / Lee, Hyosung; Park, Ki Duk; Yang, Xiao Fang; Dustrude, Erik T.; Wilson, Sarah M.; Khanna, Rajesh; Kohn, Harold.

In: Journal of Medicinal Chemistry, Vol. 56, No. 14, 25.07.2013, p. 5931-5939.

Research output: Research - peer-reviewArticle

Lee, H, Park, KD, Yang, XF, Dustrude, ET, Wilson, SM, Khanna, R & Kohn, H 2013, '(Biphenyl-4-yl)methylammonium chlorides: Potent anticonvulsants that modulate Na+ currents' Journal of Medicinal Chemistry, vol 56, no. 14, pp. 5931-5939. DOI: 10.1021/jm4007092
Lee H, Park KD, Yang XF, Dustrude ET, Wilson SM, Khanna R et al. (Biphenyl-4-yl)methylammonium chlorides: Potent anticonvulsants that modulate Na+ currents. Journal of Medicinal Chemistry. 2013 Jul 25;56(14):5931-5939. Available from, DOI: 10.1021/jm4007092
Lee, Hyosung ; Park, Ki Duk ; Yang, Xiao Fang ; Dustrude, Erik T. ; Wilson, Sarah M. ; Khanna, Rajesh ; Kohn, Harold. / (Biphenyl-4-yl)methylammonium chlorides : Potent anticonvulsants that modulate Na+ currents. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 14. pp. 5931-5939
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