Department of Pharmacology, Emory University School of Medicine, 5025 Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA.
Trends Pharmacol Sci. 2011 Dec;32(12):726-33. doi: 10.1016/j.tips.2011.08.003. Epub 2011 Oct 11.
N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diversity of NMDA receptors and are distinctly expressed during development and among brain regions. Thus, subunit-selective antagonists and modulators that differentially target the GluN2 subunit might provide an opportunity to pharmacologically modify the function of select groups of neurons for therapeutic gain. A flurry of clinical, functional and chemical studies have together reinvigorated efforts to identify subunit-selective modulators of NMDA receptor function, resulting in a handful of new compounds that appear to act at novel sites. Here, we review the properties of new emerging classes of subunit-selective NMDA receptor modulators, which we predict will mark the beginning of a productive period of progress for NMDA receptor pharmacology.
N-甲基-D-天冬氨酸（NMDA）受体是包含四个可能的 GluN2 亚基中的两个的四聚体离子通道。这些受体几十年来一直与中风、创伤性脑损伤、痴呆和精神分裂症等神经系统疾病有关。GluN2 亚基对 NMDA 受体的功能多样性有很大贡献，并且在发育过程中和大脑区域之间有明显的表达。因此，亚基选择性拮抗剂和调节剂可以有区别地针对 GluN2 亚基，从而为治疗性获益提供机会，以改变特定神经元群体的功能。大量的临床、功能和化学研究共同激发了识别 NMDA 受体功能的亚基选择性调节剂的努力，产生了少数几种似乎作用于新位点的新化合物。在这里，我们回顾了新兴的亚基选择性 NMDA 受体调节剂类别的特性，我们预计这将标志着 NMDA 受体药理学取得富有成效的进展的开始。
