Muguruza Carolina, Meana J Javier, Callado Luis F
Department of Pharmacology, University of the Basque Country, UPV/EHULeioa, Spain; Centro de Investigación Biomédica en Red de Salud MentalMadrid, Spain.
Front Pharmacol. 2016 May 20;7:130. doi: 10.3389/fphar.2016.00130. eCollection 2016.
Schizophrenia is a chronic psychiatric disorder which substantially impairs patients' quality of life. Despite the extensive research in this field, the pathophysiology and etiology of schizophrenia remain unknown. Different neurotransmitter systems and functional networks have been found to be affected in the brain of patients with schizophrenia. In this context, postmortem brain studies as well as genetic assays have suggested alterations in Group II metabotropic glutamate receptors (mGluRs) in schizophrenia. Despite many years of drug research, several needs in the treatment of schizophrenia have not been addressed sufficiently. In fact, only 5-10% of patients with schizophrenia successfully achieve a full recovery after treatment. In recent years mGluRs have turned up as novel targets for the design of new antipsychotic medications for schizophrenia. Concretely, Group II mGluRs are of particular interest due to their regulatory role in neurotransmission modulating glutamatergic activity in brain synapses. Preclinical studies have demonstrated that orthosteric Group II mGluR agonists exhibit antipsychotic-like properties in animal models of schizophrenia. However, when these compounds have been tested in human clinical studies with schizophrenic patients results have been inconclusive. Nevertheless, it has been recently suggested that this apparent lack of efficacy in schizophrenic patients may be related to previous exposure to atypical antipsychotics. Moreover, the role of the functional heterocomplex formed by 5-HT2A and mGlu2 receptors in the clinical response to Group II mGluR agonists is currently under study.
精神分裂症是一种慢性精神疾病，严重损害患者的生活质量。尽管该领域已有广泛研究，但精神分裂症的病理生理学和病因仍不明晰。研究发现，精神分裂症患者大脑中的不同神经递质系统和功能网络受到影响。在此背景下，尸检脑研究以及基因检测表明，精神分裂症患者的Ⅱ型代谢型谷氨酸受体（mGluRs）发生了改变。尽管多年来一直在进行药物研究，但精神分裂症治疗中的一些需求仍未得到充分满足。事实上，只有5%至10%的精神分裂症患者在治疗后能成功实现完全康复。近年来，mGluRs已成为设计新型抗精神分裂症药物的新靶点。具体而言，Ⅱ型mGluRs因其在调节大脑突触中谷氨酸能活性的神经传递中的调节作用而备受关注。临床前研究表明，Ⅱ型mGluR的正构激动剂在精神分裂症动物模型中表现出抗精神病样特性。然而，当这些化合物在精神分裂症患者的人体临床研究中进行测试时，结果并不确定。尽管如此，最近有人提出，在精神分裂症患者中这种明显的疗效缺乏可能与先前接触非典型抗精神病药物有关。此外，目前正在研究由5-HT2A和mGlu2受体形成的功能性异源复合物在对Ⅱ型mGluR激动剂的临床反应中的作用。
