Discovery Pharmacology, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Curr Pharm Des. 2011;17(2):94-102. doi: 10.2174/138161211795049570.
The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. Among the glutamate receptors, metabotropic receptors (mGlu receptors) have emerged as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. Among them, group II mGlu receptors, such as mGlu2 and mGlu3 receptors, are of particular interest because of their unique distribution and the regulatory roles they have in neurotransmission. Recently, potent agonists for mGlu2/3 receptor have been synthesized, and their pharmacological roles have been intensively investigated in animal models. The efficacy for the treatment of schizophrenia has also been proven in a clinical trial. Recently, much attention has been paid to mGlu2 receptor potentiators, which potentiate the glutamate response without affecting the actual activity of the mGlu2 receptor. In addition, mGlu1 receptor antagonists have recently been proposed as an attractive approach to developing novel antipsychotics in animal models. This review describes the potential of both mGlu2/3 receptor agonists/potentiators and mGlu1 receptor antagonists for the treatment of schizophrenia.
谷氨酸能系统参与大脑中的广泛的生理过程，其功能障碍在精神疾病（包括精神分裂症）的病因学和发病生理学中起着重要作用。在谷氨酸受体中，代谢型谷氨酸受体（mGlu 受体）作为开发新型精神疾病干预措施的有吸引力的治疗靶点而备受关注。其中，II 组 mGlu 受体（如 mGlu2 和 mGlu3 受体）因其独特的分布和在神经传递中的调节作用而特别引人注目。最近，已经合成了强效的 mGlu2/3 受体激动剂，并在动物模型中对其药理学作用进行了深入研究。在临床试验中也证明了它们治疗精神分裂症的疗效。最近，人们对 mGlu2 受体增效剂给予了极大的关注，mGlu2 受体增效剂增强谷氨酸的反应而不影响 mGlu2 受体的实际活性。此外，mGlu1 受体拮抗剂最近也被提出作为在动物模型中开发新型抗精神病药物的一种有吸引力的方法。本文综述了 mGlu2/3 受体激动剂/增效剂和 mGlu1 受体拮抗剂治疗精神分裂症的潜力。
