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Subtype selectivity of α+β− site ligands of GABA A receptors: identification of the first highly specific positive modulators at α6β2/3γ2 receptors
Author(s) -
Varagic Zdravko,
Ramerstorfer Joachim,
Huang Shengming,
Rallapalli Sundari,
SartoJackson Isabella,
Cook James,
Sieghart Werner,
Ernst Margot
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12153
Subject(s) - receptor , gabaa receptor , selectivity , identification (biology) , chemistry , binding site , biochemistry , biology , botany , catalysis
GABAA receptors are the major inhibitory neurotransmitter receptors in the mammalian brain and the target of many clinically important drugs interacting with different binding sites. Recently, we demonstrated that CGS 9895 (2-(4-methoxyphenyl)-2H-pyrazolo[4,3-c]quinolin-3(5H)-one) elicits a strong and subtype-dependent enhancement of GABA-induced currents via a novel drug-binding site at extracellular αx+βy- (x = 1-6, y = 1-3) interfaces. Here, we investigated 16 structural analogues of CGS 9895 for their ability to modulate GABA-induced currents of various GABAA receptor subtypes.