Figure 1.

The identified small-molecule ligands 2027 and 018 are antagonists at GABA_ΑRs. (A) Chemical structures of 018, 2027, GABA and Gabazine. (B) Results of primary screening of the compound library at α₄β₁δ receptors in antagonist mode in the FMP assay (96-well format). Data shown are normalized to GABA EC₈₀ of compounds tested in 10 μM in singlicates. (C) Concentration-response curves of 2027 and 018 at α₄β₁δ receptors, with gabazine shown as reference. (D) Concentration-response curves of 018 at selected GABA_Α receptor subtypes showing α-subunit dependent inhibition of the GABA EC₈₀ signal. (E) Concentration-response curves of 2027 and gabazine at α₄β₁δ and α₄β₁γ₂ showing a subtype-dependent right shift of the curve only for 2027. Data are shown as representative curves obtained in the FMP assay with three technical replicates (means ± SD). Collected IC₅₀ values ± SEM and GABA EC₈₀ values are given in Table 1.