Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee 37232, USA.
ACS Chem Neurosci. 2011 Aug 17;2(8):382-93. doi: 10.1021/cn200008d. Epub 2011 Apr 12.
Group II metabotropic glutamate (mGlu) receptors consist of the metabotropic glutamate 2 (mGlu(2)) and metabotropic glutamate 3 (mGlu(3)) receptor subtypes which modulate glutamate transmission by second messenger activation to negatively regulate the activity of adenylyl cyclase. Excessive accumulation of glutamate in the perisynaptic extracellular region triggers mGlu(2) and mGlu(3) receptors to inhibit further release of glutamate. There is growing evidence that the modulation of glutamatergic neurotransmission by small molecule modulators of Group II mGlu receptors has significant potential for the treatment of several neuropsychiatric and neurodegenerative diseases. This review provides an overview of recent progress on the synthesis and pharmacological characterization of positive and negative allosteric modulators of the Group II mGlu receptors.
II 组代谢型谷氨酸（mGlu）受体包括代谢型谷氨酸 2（mGlu(2)）和代谢型谷氨酸 3（mGlu(3)）受体亚型，通过第二信使激活来调节谷氨酸传递，从而负调控腺苷酸环化酶的活性。细胞外突触间隙中谷氨酸的过度积累会触发 mGlu(2)和 mGlu(3)受体抑制谷氨酸的进一步释放。越来越多的证据表明，通过 II 组 mGlu 受体的小分子调节剂来调节谷氨酸能神经递质传递，对于治疗多种神经精神疾病和神经退行性疾病具有重要的潜在作用。本文综述了 II 组 mGlu 受体的正变构和负变构调节剂的合成和药理学特性的最新进展。
