새로운 Quinoxalinedione계 신약 KU-4162의 NMDA수용체 선택성 = Selectivity of KY-4162, a Novel Quinoxalinedione Derivative, for NMDA Receptors

다국어 초록 (Multilingual Abstract)

Antagonists for glycine binding site of NMDA receptors have advantage over those of NMDA receptors in terms of their side effects. In this study, the receptor binding profile of KJ-4162, a newly synthesized quinoxalinedione-derived antagonist for glycine binding site of NMDA receptors, was characterized using radioreceptor binding assays. The experimental condition of ligand binding assay of [³H]MK-80] for NMDA channel, [³H]kinate for kinate receptors, amino-3-hydroxy-5-methylisoxazole-4-propinc acid, DL-[5-methy]- ³H] ([³H]AMPA) for AMPA receptors, and [³H]MDL 105,519 for glycine-binding sites of NMDA receptors were established in rat cerebral cortex membranes. The range of specific binding is appeared to acceptable (65-98%). MDL 105,519, ACEA-1,021, glycine, 5,7-dichlorokynurenic acid (DCKY), and 6,7-dichloroquinoxalline-2,3-dione (DCQX) displaced the specific binding of [³H]MDL 105,519 with different binding affinity. KJ-4162 displaced the specific binding of [³H]MDL 105.519, and its apparent affinity constant (76.2±1.0 nM) was lower than that of MDL 105,519, ACEA-1,021, DCKY or glycine, but higher than that of DCQX and L-695,902. KJ-4162 (1 цΜ) displaced specific binding of [³H]MDL 105,519 by about 90%, but showed little influence on the specific bindings of [³H]kinate and [³H]AMPA. These results indicate that KJ-4162 is a novel and potent antagonist for glycine binding site of NMDA receptor complex. As well, this compound could possess neuroprotective effect.