Subtype selectivity of α+β- site ligands of GABAA receptors: identification of the first highly specific positive modulators at α6β2/3γ2 receptors.

ABSTRACT:

Background and purpose

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.

Experimental approach

Recombinant GABAA receptor subtypes were expressed in Xenopus laevis oocytes and investigated by the two-electrode voltage clamp method.

Key results

SUBMITTER: Varagic Z 

PROVIDER: S-EPMC3651664 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature