Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Trends Pharmacol Sci. 2011 Jul;32(7):420-34. doi: 10.1016/j.tips.2011.03.006. Epub 2011 Apr 13.
Although lithium has largely met its initial promise as the first drug discovered in the modern era of psychopharmacology, to date no definitive mechanism for its effects has been established. It has been proposed that lithium exerts its therapeutic effects by interfering with signal transduction through G-protein-coupled receptor (GPCR) pathways or direct inhibition of specific targets in signaling systems, including inositol monophosphatase and glycogen synthase kinase-3 (GSK-3). Recently, increasing evidence has suggested that N-methyl-D-aspartate receptor (NMDAR)/nitric oxide (NO) signaling could mediate some lithium-induced responses in the brain and peripheral tissues. However, the probable role of the NMDAR/NO system in the action of lithium has not been fully elucidated. In this review, we discuss biochemical, preclinical/behavioral and physiological evidence that implicates NMDAR/NO signaling in the therapeutic effect of lithium. NMDAR/NO signaling could also explain some of side effects of lithium.
尽管锂在很大程度上满足了其作为精神药理学现代时代发现的第一种药物的最初承诺，但迄今为止，尚未确定其作用的确切机制。有人提出，锂通过干扰 G 蛋白偶联受体 (GPCR) 途径的信号转导或直接抑制信号系统中的特定靶标（包括肌醇单磷酸酶和糖原合酶激酶-3 (GSK-3)）来发挥其治疗作用。最近，越来越多的证据表明，N-甲基-D-天冬氨酸受体 (NMDAR)/一氧化氮 (NO) 信号可能介导锂在大脑和外周组织中引起的一些反应。然而，NMDAR/NO 系统在锂作用中的可能作用尚未完全阐明。在这篇综述中，我们讨论了生化、临床前/行为和生理学证据，这些证据表明 NMDAR/NO 信号参与了锂的治疗作用。NMDAR/NO 信号也可以解释锂的一些副作用。
