Research Headquarters, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Int J Mol Sci. 2019 Mar 13;20(6):1270. doi: 10.3390/ijms20061270.
Numerous studies have demonstrated the antidepressant effects of group II metabotropic glutamate (mGlu2/3) receptor antagonists in various rodent models. Importantly, it has been shown that the antidepressant effects of mGlu2/3 receptor antagonists in rodent models are similar to those of ketamine, which exerts rapid and long-lasting antidepressant effects in patients with major depressive disorders, including patients with treatment-resistant depression. In addition, the synaptic mechanisms underlying the effects of mGlu2/3 receptor antagonists are reported to be similar to those underlying the effects of ketamine. The roles of the serotonergic system in the antidepressant effects of mGlu2/3 receptor antagonists have recently been demonstrated. Moreover, it was investigated how mGlu2/3 receptor antagonists interact with the serotonergic system to exert antidepressant effects. Notably, the same neural mechanisms as those underlying the effects of ketamine may be involved in the antidepressant actions of the mGlu2/3 receptor antagonists. In this review, we shall summarize the antidepressant potential of mGlu2/3 receptor antagonists and their mechanisms of action in comparison with those of ketamine. In particular, we shall focus on the roles of the serotonergic system in the antidepressant actions of mGlu2/3 receptor antagonists.
大量研究表明，II 型代谢型谷氨酸（mGlu2/3）受体拮抗剂在各种啮齿动物模型中具有抗抑郁作用。重要的是，已经表明，mGlu2/3 受体拮抗剂在啮齿动物模型中的抗抑郁作用与氯胺酮相似，氯胺酮对包括治疗抵抗性抑郁症患者在内的重度抑郁症患者具有快速和持久的抗抑郁作用。此外，据报道，mGlu2/3 受体拮抗剂作用的突触机制与氯胺酮的作用机制相似。最近已经证明了 5-羟色胺能系统在 mGlu2/3 受体拮抗剂抗抑郁作用中的作用。此外，还研究了 mGlu2/3 受体拮抗剂如何与 5-羟色胺能系统相互作用发挥抗抑郁作用。值得注意的是，与氯胺酮作用相关的相同神经机制可能涉及 mGlu2/3 受体拮抗剂的抗抑郁作用。在这篇综述中，我们将总结 mGlu2/3 受体拮抗剂的抗抑郁潜力及其与氯胺酮相比的作用机制。特别是，我们将重点介绍 5-羟色胺能系统在 mGlu2/3 受体拮抗剂抗抑郁作用中的作用。
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