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(2R,4R)-APDC

现货
Catalog No.
B6634
组II代谢型谷氨酸受体激动剂
组合的产品项目
规格价格库存 数量
10mg
¥ 5,488.00
Ship with 10-15 days

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Background

EC50: 0.4 μM

2R,4R-APDC is a highly selective and relatively potent group II metabotropic glutamate receptor agonist for human mGlu2. L-Glutamate (Glu) is EAA neurotransmitter in the mammalian CNS. Its effects are mediated by a variety of presynaptic and postsynaptic neuronal receptors.

In vitro: 2R,4R-APDC blocked forskolin-stimulated cAMP with none of the other activities of lS,3R-ACPD. forskolin-stimulated cAMP formation in human mGluR2 expressing cells with about three-fold greater potency than lS,3R-ACPD were also inhibited by 2R,4R-APDC, which, unlike lS,3R-ACPD, exhibited no appreciable activation of phosphoinostide hydrolysis in human mGluR. Thus, 2R,4R-APDC should be a useful pharmacological tool to explore the functions of mGluRs coupled to inhibition of adenylate cyclase [1]. The effects of four isomers of APDC were investigated at glutamate receptors in vitro. (2R,4R)-APDC, an aza analog of the nonselective mGluR agonist (1S,3R)-ACPD possessed relatively high affinity for metabotropic glutamate receptors (mGluRs) with no effects on radioligand binding to NMDA, AMPA, or kainate receptors up to 100 íM. None of the other APDC isomers exhibited significant mGluR binding affinity, indicating that this interaction is highly stereospecific [2].

In vivo: Both (1S,3R)-ACPD and (2R,4R)-APDC were effectively attenuating forskolin-stimulated cAMP formation in the adult rat cerebral cortex; however, while (1S,3R)-ACPD was also effectively stimulating basal tritiated inositol monophosphate production of the neonatal rat cerebral cortex, (2R,4R)-APDC was not effectively stimulating phosphoinositide hydrolysis in this tissue preparation. An augmentation of AMPA-induced excitation was produced by microelectrophoretic application of either (1S,3R)-ACPD or (2R,4R)-APDC to intact rat spinal neurons [2].

Clinical trial: Clinical study has been conducted.

References:
[1] Schoepp DD, Johnson BG, Salhoff CR, Valli MJ, Desai MA, Burnett JP, Mayne NG, Monn JA.  Selective inhibition of forskolin-stimulated cyclic AMP formation in rat hippocampus by a novel mGluR agonist, 2R,4R-4-aminopyrrolidine-2,4- dicarboxylate. Neuropharmacology. 1995 Aug;34(8):843-50.
[2] Monn JA, Valli MJ, Johnson BG, Salhoff CR, Wright RA, Howe T, Bond A, Lodge D, Spangle LA, Paschal JW, Campbell JB, Griffey K, Tizzano JP, Schoepp DD.  Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase. J Med Chem. 1996 Jul 19; 39 (15):2990-3000.

Chemical Properties

Physical AppearanceWhite solid
StorageDesiccate at RT
M.Wt174.16
Cas No.169209-63-6
FormulaC6H10N2O4
SolubilitySoluble to 100 mM in H2O
Chemical Name(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid
SDFDownload SDF
Canonical SMILESOC([C@]1(C[C@H](C(O)=O)NC1)N)=O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

酶学实验 [1]:

结合实验

分别使用[3H]CGS19755,[3H]AMPA,[3H]海酸盐和[3H]谷氨酸盐作为放射性配体,进行与NMDA,AMPA,红藻氨酸和代谢型谷氨酸受体的放射性结合试验。测量大鼠大脑皮质切片中的环磷酸腺苷(cAMP)和氚标肌酸单磷酸([3H]IP)水平。

细胞实验 [2]:

细胞系

表达人mGluR2的CHO细胞

溶解方法

在无菌水中的溶解度高达100 mM。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

37℃下孵育20分钟。

应用

(2R,4R)-APDC抑制表达人mGluR2细胞中由于forskolin刺激形成的cAMP,该活性要高于lS,3R-ACPD。但与lS,3R-ACPD不同的是,(2R,4R)-APDC在人mGluR.lcc表达细胞中并不能明显地激活其磷酸肌醇水解。.

动物实验 [1]:

动物模型

将雌性Wistar大鼠用戊巴比妥钠麻醉,进行腰椎板切除术以便将玻璃微电极插入脊髓灰质。连续记录响应AMPA(10mM in 200mM NaCl,pH 7.4)的单个神经元的动作电位发射率。

剂量

当建立亚最大响应时,溶解在175mM NaCl(pH 7.4)中的25mM (2R,4R)-APDC被注射到不同的细胞上。

应用

(2R,4R)-APDC使大鼠脊髓神经元由AMPA诱发反应的响应增强。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Monn JA, et al. Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase. J Med Chem. 1996 Jul 19;39(15):2990-3000.

[2] Schoepp DD, et al. Selective inhibition of forskolin-stimulated cyclic AMP formation in rat hippocampus by a novel mGluR agonist, 2R,4R-4-aminopyrrolidine-2,4- dicarboxylate. Neuropharmacology. 1995 Aug;34(8):843-50.

质量控制

质量控制和MSDS

批次:

化学结构

(2R,4R)-APDC