Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, USA.
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4700-3. doi: 10.1016/j.bmcl.2010.04.143. Epub 2010 May 5.
Administration of Neuropeptide S (NPS) has been shown to produce arousal, that is, independent of novelty and to induce wakefulness by suppressing all stages of sleep, as demonstrated by EEG recordings in rat. Medicinal chemistry efforts have identified a quinolinone class of potent NPSR antagonists that readily cross the blood-brain barrier. We detail here optimization efforts resulting in the identification of a potent NPSR antagonist which dose-dependently and specifically inhibited (125)I-NPS binding in the CNS when administered to rats.
给予神经肽 S（NPS）会产生觉醒作用，即独立于新奇感，并通过抑制睡眠的所有阶段来诱导觉醒，这在大鼠的 EEG 记录中得到了证明。药物化学研究已经确定了一类有效的 NPSR 拮抗剂，它们很容易穿过血脑屏障。我们在此详细介绍了优化工作，结果鉴定出一种有效的 NPSR 拮抗剂，当给予大鼠时，该拮抗剂剂量依赖性且特异性地抑制了中枢神经系统中（125）I-NPS 的结合。
