GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists.
GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists.
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Glyx-13，NMDA受体甘氨酸位点功能性局部激动剂可增强认知并产生抗抑郁作用，而没有NMDA受体拮抗剂的心理副作用。
DOI：
10.1517/13543784.2014.852536
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发表时间：
2014-02
影响因子：
6.1
通讯作者：
Leander JD
中科院分区：
文献类型：
--
作者：
Moskal JR;Burch R;Burgdorf JS;Kroes RA;Stanton PK;Disterhoft JF;Leander JD
N-甲基-d-天冬氨酸受体-离子载体复合体在学习和记忆中起关键作用，对患有情感障碍的动物和人类具有疗效。GLYX-13是一种N-甲基-d-天冬氨酸受体(NMDAR)甘氨酸功能部分激动剂和认知增强剂，也显示出快速的抗抑郁活性，没有精神障碍副作用。作者综述了GLYX-13的作用机制，已在临床前研究和临床研究中进行了评估。具体地说，作者综述了它的药理、药代动力学和临床研究中证明的药物安全性。NMDAR完全拮抗剂可以在治疗耐药的受试者中产生快速的抗抑郁作用；然而，它们往往伴随着拟精神分裂的效应，这使得在临床试验住院环境外长期使用成为问题。GLYX-13似乎通过NMDAR触发的突触可塑性在额叶皮质发挥其抗抑郁作用。了解GLYX-13‘S抗抑郁作用的机制基础将为谷氨酸能系统在抑郁症中的作用提供新的见解，并为治疗开发确定新的靶点。
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.