A GABAA receptor antagonist
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].
参考文献:
[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.
SR 95531 氢溴酸盐 (Gabazine) 是 GABAA 受体上 GABA 结合位点的选择性拮抗剂 [1]。 SR 95531 氢溴酸盐部分抑制巴比妥类戊巴比妥和类固醇阿尔法索酮对受体的直接激活，可能是作为 GABAA 受体通道开放的变构抑制剂[2]。
SR 95531 hydrobromide 对 GABA 和重组 α1β2γ2S GABAA 受体的结合具有拮抗作用，IC50 为 349 nM [1]。竞争性拮抗剂 SR 95531 hydrobromide 对两种细胞类型显示相似的效力，对 α4β3γ2 受体和 α4β3δ 受体的 IC50 分别为 196 nM 和 224 nM [3]。在 αTC1-9 细胞中，GABA (10 μmol/l) 将胰高血糖素分泌显着抑制至对照水平的 50%，而在 SR 95531 氢溴酸盐 (10 μmol/l) 存在的情况下，外源性 GABA 对胰高血糖素分泌没有显着影响 < sup>[4].
SR 95531 氢溴酸盐给药于它。有效减弱 it 诱导的抗伤害作用给予续断皂甙 C (DSC) [5]。
| Animal experiment [1]: | |
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Animal models |
Male ICR mice |
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Preparation Method |
Effects of 5-aminovaleric acid (5-AVA) and SR 95531 injected intrathecally (i.t.) on inhibition of the tail-flick response induced by DSC administered i.t. Saline (5 μl), 5-AVA (from 1 to 20 μg) or SR 95531 (from 0.1 to 2 ng) was pretreated i.t. 10 min before i.t. administration of DSC (30 μg) or vehicle. |
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Dosage form |
injected intrathecally, 0.1 to 2 ng |
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Applications |
SR 95531 attenuated i.t. administered DSC-induced inhibition of the tail-flick response in a dose-dependent manner. |
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参考文献: [1]: 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. | |
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