Robinson M B, Schulte M K, Freund R K, Johnson R L, Koerner J F
Brain Res. 1985 Dec 30;361(1-2):19-24. doi: 10.1016/0006-8993(85)91270-3.
Eight kynurenic acid analogues were bath-applied to rat hippocampal slices while recording extracellular synaptic field potentials and the potencies of these analogues for inhibition of these responses were compared to that of kynurenic acid. Quinaldic acid, 4-hydroxyquinoline, 4-hydroxypicolinic acid, L-kynurenine and picolinic acid inhibited evoked field potentials, but were at least 15-fold less potent than kynurenic acid in all pathways tested. Xanthurenic acid was inactive in the pathways tested. Quinolinic acid and dipicolinic acid showed signs of agonist activity with IC50's of approx. 400 microM and 2500 microM, respectively. These studies show that the 2-carboxy group and the 4-hydroxy moiety are essential for the antagonist activity exhibited by kynurenate. They also show that the unsubstituted second aromatic ring greatly enhances the affinity of kynurenate for these receptors and that substitution in at least one position on this aromatic ring abolishes activity.
在记录细胞外突触场电位时，将八种犬尿喹啉酸类似物浴用在大鼠海马切片上，并将这些类似物抑制这些反应的效力与犬尿喹啉酸的效力进行比较。喹哪啶酸、4-羟基喹啉、4-羟基吡啶甲酸、L-犬尿氨酸和吡啶甲酸抑制诱发的场电位，但在所有测试途径中其效力至少比犬尿喹啉酸低15倍。黄尿酸在所测试的途径中无活性。喹啉酸和二吡啶甲酸显示出激动剂活性迹象，其IC50分别约为400微摩尔和2500微摩尔。这些研究表明，2-羧基和4-羟基部分对于犬尿酸盐表现出的拮抗剂活性至关重要。它们还表明，未取代的第二个芳香环极大地增强了犬尿酸盐对这些受体的亲和力，并且该芳香环上至少一个位置的取代会消除活性。
