From the Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.
Harv Rev Psychiatry. 2018 Nov/Dec;26(6):307-319. doi: 10.1097/HRP.0000000000000183.
After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies. Here, we highlight the evidence supporting the antidepressant effects of various glutamatergic modulators, including (1) broad glutamatergic modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta], AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC-301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and (4) metabotropic glutamate receptor modulators (AZD2066, RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).
参加此活动后，学习者应能够更好地评估支持谷氨酸能调节剂抗抑郁作用的证据。临床前和临床研究都表明，谷氨酸能系统功能障碍与心境障碍（如双相抑郁和重性抑郁障碍）的病理生理学有关。特别是，在重性抑郁障碍或双相抑郁障碍患者中，给予亚麻醉剂量的谷氨酸能调节剂氯胺酮后，抑郁症状迅速减轻。这些结果促使人们重新利用或开发其他谷氨酸能调节剂，无论是作为单一疗法还是作为其他疗法的辅助治疗。在这里，我们强调了各种谷氨酸能调节剂的抗抑郁作用的证据，包括（1）广泛的谷氨酸能调节剂（氯胺酮、艾司氯胺酮、右美沙芬、右美沙芬-奎尼丁[Nuedexta]、AVP-786、一氧化二氮[N2O]、AZD6765），（2）亚基（NR2B）特异性 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（CP-101,606/特拉佐罗迪尔、MK-0657[CERC-301]），（3）甘氨酸部位部分激动剂（D-环丝氨酸、GLYX-13、肌氨酸、AV-101）和（4）代谢型谷氨酸受体调节剂（AZD2066、RO4917523/巴米谷氨酸、JNJ40411813/ADX71149、R04995819[RG1578]）。
