SR 95531 hydrobromide (Gabazine) to be a selective antagonist at the GABA binding sites on GABAA receptors [1]. SR 95531 hydrobromide partially inhibited direct activation of the receptor by the barbiturate pentobarbital and by the steroid alphaxolone, possibly by acting as an allosteric inhibitor of GABAA receptor channel opening [2].
SR 95531 hydrobromide had antagonist potency response against to the binding of GABA and recombination α1β2γ2S GABAA receptors, with the IC50 of 349 nM [1]. The competitive antagonist SR 95531 hydrobromide showed similar potency on both cell types with IC50's of 196 nM and 224 nM on α4β3γ2 receptors and α4β3δ receptors respectively [3]. In αTC1-9 cells, GABA (10 µmol/l) significantly suppressed glucagon secretion to ∼50% of control levels, whereas in the presence of SR 95531 hydrobromide (10 µmol/l), exogenous GABA exerted no significant effect on glucagon secretion [4].
SR 95531 hydrobromide administered i.t. effectively attenuated antinociception induced by i.t. administered Dipsacus saponin C (DSC) [5].
References:
[1]. Iqbal F, Ellwood R, Mortensen M, et al. Synthesis and evaluation of highly potent GABAA receptor antagonists based on gabazine (SR-95531)[J]. Bioorganic & medicinal chemistry letters, 2011, 21(14): 4252-4254.
[2]. Ueno S, Bracamontes J, Zorumski C, et al. Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor[J]. Journal of Neuroscience, 1997, 17(2): 625-634.
[3]. Brown N, Kerby J, Bonnert T P, et al. Pharmacological characterization of a novel cell line expressing human α4β3δ GABAA receptors[J]. British journal of pharmacology, 2002, 136(7): 965-974.
[4]. Bailey S J, Ravier M A, Rutter G A. Glucose-dependent regulation of γ-aminobutyric acid (GABAA) receptor expression in mouse pancreatic islet α-cells[J]. Diabetes, 2007, 56(2): 320-327.
[5]. Suh H W, Song D K, Huh S O, et al. Antinociceptive mechanisms of Dipsacus saponin C administered intrathecally in mice[J]. Journal of ethnopharmacology, 2000, 71(1-2): 211-218.