Targeting of NMDA Receptors in the Treatment of Major Depression
Targeting of NMDA Receptors in the Treatment of Major Depression
复制标题
NMDA 受体靶向治疗重度抑郁症
DOI：
10.2174/1381612819666140110120435
复制
发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
--
作者：
Dang, Yong-Hui;Ma, Xian-Cang;Hashimoto, Kenji
重度抑郁症 (MDD) 是一种常见的、反复发作的精神疾病，影响着全世界数百万人。越来越多的证据表明，N-甲基-D-天冬氨酸（NMDA）受体（谷氨酸受体的一种亚型）在神经生物学和该疾病的治疗中发挥着重要作用。目前，非竞争性NMDA受体拮抗剂氯胺酮被认为是治疗难治性抑郁症最有吸引力的候选药物之一。最近的一项研究表明，氯胺酮对难治性抑郁症和双相情感障碍患者具有快速抗抑郁活性。氯胺酮输注后 24 小时的反应率为 25% 至 85%，输注后 72 小时为 14% 至 70%，一般有轻微的不良反应。基于 NMDA 受体在抑郁症中的作用，已经开发了许多与该受体相互作用的治疗药物。在本文中，我们回顾了有关谷氨酸信号传导在 MDD 神经生物学中的作用的最新发现，以及潜在的新型治疗药物，如氯胺酮、美金刚、AZD6765、traxoprodil、MK-0657、GLYX-13、NRX-1047、D-环丝氨酸、肌氨酸，所有这些药物都针对该系统。
Major depressive disorder (MDD) is a common, recurrent mental illness that affects millions of people worldwide. Accumulating evidence suggests that the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptors, plays an important role in the neurobiology and treatment of this disease. Currently, the non-competitive NMDA receptor antagonist ketamine is considered as one of the most attractive candidate drugs in therapy of treatment-resistant depression. A recent study demonstrated ketamine's rapid antidepressant activity in patients with treatment-resistant MDD and bipolar disorder. The response rate for ketamine ranged from 25% to 85% at 24 hours post-infusion and from 14% to 70% at 72 hours post-infusion, with generally mild adverse effects. Based on the role of the NMDA receptor in depression, a number of therapeutic drugs which interact with this receptor have been developed. In this article, we reviewed recent findings concerning the role of glutamatergic signaling in the neurobiology of MDD and potential, novel therapeutic drugs, such as ketamine, memantine, AZD6765, traxoprodil, MK-0657, GLYX-13, NRX-1047, D-cycloserine, sarcosine, all of which target this system.