Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia.
Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia.
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DOI：
10.1016/j.tips.2008.10.006
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发表时间：
2009-01
影响因子：
13.8
通讯作者：
Jones CK
中科院分区：
文献类型：
--
作者：
Conn PJ;Lindsley CW;Jones CK
近年来，代谢型谷氨酸（mGlu）受体已成为治疗一系列中枢神经系统疾病的潜在新药物靶点。在靶向特定mGlu受体亚型方面取得了一些最引人注目的进展，这是治疗精神分裂症的一种全新方法。最近的动物和临床研究提供了强有力的证据表明，II组mGlu受体（mGluR2和mGluR3）的激动剂是有效的精神分裂症的阳性症状的治疗，和动物研究表明，mGluR5激动剂可以提供一种新的方法，用于治疗所有主要症状域（阳性，阴性，和认知）的这种疾病。尽管发现这些受体的选择性激动剂是一个挑战，但最近在发现mGluR2和mGluR5的高选择性正变构调节剂（PAM）方面取得了进展。这些mGlu受体选择性PAM具有作为临床候选物优化所需的性质，并且在预测精神分裂症治疗功效的动物模型中具有稳健的作用。
In recent years, the metabotropic glutamate (mGlu) receptors have emerged as potential new drug targets for treatment of a range of CNS disorders. Some of the most compelling advances have been made in targeting specific mGlu receptor subtypes as a fundamentally new approach to the treatment of schizophrenia. Recent animal and clinical studies provide strong evidence that agonists of group II mGlu receptors (mGluR2 and mGluR3) are effective in the treatment of the positive symptoms of schizophrenia, and animal studies suggest that mGluR5 agonists could provide a novel approach for the treatment of all major symptom domains (positive, negative, and cognitive) of this disorder. Although the discovery of selective agonists of these receptors is a challenge, there have been recent advances in the discovery of highly selective positive allosteric modulators (PAMs) of mGluR2 and mGluR5. These mGlu receptor-selective PAMs have properties needed for optimization as clinical candidates and have robust effects in animal models that predict efficacy in treatment of schizophrenia.
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影响因子：
--
作者：
Conn, P. Jeffrey;Tamminga, Carol;Lindsley, Craig
通讯作者：
Lindsley, Craig
影响因子：
--
作者：
Aghajanian, GK;Marek, GJ
通讯作者：
Marek, GJ
影响因子：
2.7
作者：
Cube, RV;Vernier, JM;Pinkerton, AB
通讯作者：
Pinkerton, AB
影响因子：
7.3
作者：
de Paulis, Tomas;Hemstapat, Kamondanai;Conn, P. Jeffrey
通讯作者：
Conn, P. Jeffrey
影响因子：
7.3
作者：
Doherty, AJ;Palmer, MJ;Collingridge, GL
通讯作者：
Collingridge, GL