Northwestern University, McCormick School of Engineering and Applied Science, Falk Center for Molecular Therapeutics, Department of Biomedical Engineering , 1801 Maple Avenue, Suite 4300, Evanston IL 60201 , USA
Expert Opin Investig Drugs. 2014 Feb;23(2):243-54. doi: 10.1517/13543784.2014.852536. Epub 2013 Nov 20.
The N-methyl-d-aspartate receptor-ionophore complex plays a key role in learning and memory and has efficacy in animals and humans with affective disorders. GLYX-13 is an N-methyl-d-aspartate receptor (NMDAR) glycine-site functional partial agonist and cognitive enhancer that also shows rapid antidepressant activity without psychotomimetic side effects.
The authors review the mechanism of action of GLYX-13 that was investigated in preclinical studies and evaluated in clinical studies. Specifically, the authors review its pharmacology, pharmacokinetics, and drug safety that were demonstrated in clinical studies.
NMDAR full antagonists can produce rapid antidepressant effects in treatment-resistant subjects; however, they are often accompanied by psychotomimetic effects that make chronic use outside of a clinical trial inpatient setting problematic. GLYX-13 appears to exert its antidepressant effects in the frontal cortex via NMDAR-triggered synaptic plasticity. Understanding the mechanistic underpinning of GLYX-13's antidepressant action should provide both novel insights into the role of the glutamatergic system in depression and identify new targets for therapeutic development.
N-甲基-D-天冬氨酸受体-离导复合物在学习和记忆中起着关键作用，并且在情感障碍的动物和人类中具有疗效。GLYX-13 是一种 N-甲基-D-天冬氨酸受体（NMDAR）甘氨酸位点功能部分激动剂和认知增强剂，具有快速抗抑郁作用，没有精神病副作用。
作者综述了 GLYX-13 的作用机制，该机制在临床前研究中进行了研究，并在临床研究中进行了评估。具体来说，作者综述了其在临床研究中表现出的药理学、药代动力学和药物安全性。
NMDAR 完全拮抗剂可在治疗抵抗的受试者中产生快速抗抑郁作用；然而，它们通常伴随着精神病副作用，这使得在临床试验之外的住院环境中进行慢性使用成为问题。GLYX-13 似乎通过 NMDAR 触发的突触可塑性在额叶皮层发挥其抗抑郁作用。了解 GLYX-13 抗抑郁作用的机制基础应既能提供谷氨酸能系统在抑郁症中的作用的新见解，又能确定治疗开发的新靶点。
