(S)-CPW 399

(S)-CPW 399是一种强效的和选择性的AMPA受体激动剂,Ki值为747 nM [1].

α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPA受体)是谷氨酸的离子型跨膜受体,在中枢神经系统中介导快速突触传递.AMPA受体由四个蛋白亚基低聚组装而成,即GluR1-4.

(S)-CPW 399是一种强效的和选择性的AMPA受体激动剂.(S)-CPW 399对GluR1\GluR2\GluR3及GluR4受体的亲和力的Ki值分别为109\218\2137及1756 nM[1].在小鼠小脑颗粒细胞中,(S)-CPW 399浓度和时间依赖性地诱发神经细胞死亡,EC50值为70 μM,且浓度依赖性地增加细胞内游离钙水平([Ca2+]i),EC50值为5 μM [2].在大鼠小脑颗粒细胞中,CPW-399增强GABAA受体δ亚基的表达,而其依赖于NMDA受体活化[3].在表达iGluR5的Sf9细胞中,(S)-CPW 399对iGluR5有亲和力,Ki值为44 nM.在非洲爪蟾卵母细胞中,(S)-CPW 399具有激动活性,对iGluR1\iGluR2\iGluR3及iGluR4受体的EC50值分别为24.9, 13.9, 224 and 34.3 μM[4].

参考文献：
[1].  Campiani G, Morelli E, Nacci V, et al. Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties. J Med Chem, 2001, 44(26): 4501-4504.
[2].  Sinclair C, Reavy H, Grieve A, et al. Inherent desensitisation-preventing properties of a novel, subtype-selective AMPA receptor agonist, (S)-CPW 399, as a possible explanation for its excitotoxic action in cultured cerebellar granule cells. Neurochem Int, 2003, 42(6): 499-510.
[3].  Salonen V, Kallinen S, Lopez-Picon FR, et al. AMPA/kainate receptor-mediated up-regulation of GABAA receptor delta subunit mRNA expression in cultured rat cerebellar granule cells is dependent on NMDA receptor activation. Brain Res, 2006, 1087(1): 33-40.
[4].  Butini S, Pickering DS, Morelli E, et al. 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators. J Med Chem, 2008, 51(20): 6614-6618.