Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
CNS Drugs. 2010 Aug;24(8):669-93. doi: 10.2165/11533230-000000000-00000.
Drugs acting at metabotropic glutamate receptors (mGluRs) are among the most promising agents under development for the treatment of psychiatric disorders. The research in this area is at a relatively early stage, as there are no drugs acting at mGluRs that have been approved for the treatment of any psychiatric disorder. However, in the areas of schizophrenia, anxiety disorders and mood disorders, research conducted in animal models appears to translate well into efficacy in human laboratory-based models of psychopathology and in preliminary clinical trials. Further, the genes coding for mGluRs are implicated in the risk for a growing number of psychiatric disorders. This review highlights the best studied mGluR strategies for psychiatry, based on human molecular genetics, studies in animal models and preliminary clinical trials. It describes the potential value of mGluR2 and mGluR5 agonists and positive allosteric modulators for the treatment of schizophrenia. It also reviews evidence that group II mGluR agonists and positive allosteric modulators as well as group I mGluR antagonists might also treat anxiety disorders and some forms of depression, while mGluR2 and group I mGluR antagonists (particularly mGluR5 antagonists) might have antidepressant properties. This review also links growing insights into the role of glutamate in the pathophysiology of these disorders to hypothesized mGluR-related treatment mechanisms.
作用于代谢型谷氨酸受体（mGluRs）的药物是目前开发用于治疗精神疾病的最有前途的药物之一。该领域的研究尚处于早期阶段，因为目前尚无作用于 mGluRs 的药物被批准用于治疗任何精神疾病。然而，在精神分裂症、焦虑症和心境障碍等领域，在动物模型中进行的研究似乎在精神病理学的人类实验室模型和初步临床试验中得到了很好的转化。此外，编码 mGluR 的基因与越来越多的精神疾病的风险有关。本综述根据人类分子遗传学、动物模型研究和初步临床试验，重点介绍了精神药理学中研究最深入的 mGluR 策略。它描述了 mGluR2 和 mGluR5 激动剂和正变构调节剂在治疗精神分裂症方面的潜在价值。它还回顾了证据表明，II 组 mGluR 激动剂和正变构调节剂以及 I 组 mGluR 拮抗剂也可能治疗焦虑症和某些形式的抑郁症，而 mGluR2 和 I 组 mGluR 拮抗剂（特别是 mGluR5 拮抗剂）可能具有抗抑郁作用。该综述还将对这些疾病病理生理学中谷氨酸作用的新认识与假设的 mGluR 相关治疗机制联系起来。
