Research Headquarters, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Trends Pharmacol Sci. 2017 Jun;38(6):569-580. doi: 10.1016/j.tips.2017.03.008. Epub 2017 Apr 13.
Based on the discovery of the robust antidepressant effects of ketamine in patients with depression, including those with treatment-resistant depression, agents acting on the glutamatergic system have drawn much attention as potential novel antidepressants. Among the agents acting on the glutamatergic system, preclinical data have indicated that the group II metabotropic glutamate (mGlu) receptors, mGlu2 and mGlu3, are attractive targets for the development of novel antidepressants. The antidepressant effects of mGlu2/3 receptor antagonists have been demonstrated in rodent models, and the synaptic and neural mechanisms underlying the antidepressant effects of these compounds have been investigated. Furthermore, these findings have indicated the similarities of the antidepressant effects and of the mechanisms underlying these effects between mGlu2/3 receptor antagonists and ketamine. Based on the results obtained hitherto, here I discuss the potential for mGlu2/3 receptor antagonists to be developed as next-generation antidepressants.
基于氯胺酮在抑郁症患者（包括治疗抵抗性抑郁症患者）中具有强大的抗抑郁作用的发现，作用于谷氨酸能系统的药物作为潜在的新型抗抑郁药引起了广泛关注。在作用于谷氨酸能系统的药物中，临床前数据表明，II 型代谢型谷氨酸（mGlu）受体 mGlu2 和 mGlu3 是开发新型抗抑郁药的有吸引力的靶点。mGlu2/3 受体拮抗剂在啮齿动物模型中显示出抗抑郁作用，并且已经研究了这些化合物抗抑郁作用的突触和神经机制。此外，这些发现表明 mGlu2/3 受体拮抗剂和氯胺酮的抗抑郁作用及其作用机制之间存在相似性。基于迄今为止获得的结果，我在这里讨论了将 mGlu2/3 受体拮抗剂开发为下一代抗抑郁药的潜力。
