Metabotropic glutamate (mGlu) receptors, a family of G-protein-coupled receptors, have been identified as novel therapeutic targets based on extensive research supporting their diverse contributions to cell signaling and physiology throughout the nervous system and important roles in regulating complex behaviors, such as cognition, reward, and movement. Thus, targeting mGlu receptors may be a promising strategy for the treatment of several brain disorders. Ongoing advances in the discovery of subtype-selective allosteric modulators for mGlu receptors has provided an unprecedented opportunity for highly specific modulation of signaling by individual mGlu receptor subtypes in the brain by targeting sites distinct from orthosteric or endogenous ligand binding sites on mGlu receptors. These pharmacological agents provide the unparalleled opportunity to selectively regulate neuronal excitability, synaptic transmission, and subsequent behavioral output pertinent to many brain disorders. Here, we review preclinical and clinical evidence supporting the utility of mGlu receptor allosteric modulators as novel therapeutic approaches to treat neuropsychiatric diseases, such as schizophrenia, substance use disorders, and stress-related disorders.

中文翻译：

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代谢型谷氨酸受体的变构调节剂作为神经精神疾病的新疗法

代谢型谷氨酸 (mGlu) 受体是 G 蛋白偶联受体家族，基于广泛的研究支持它们对整个神经系统的细胞信号传导和生理学的不同贡献以及在调节复杂行为中的重要作用，已被确定为新的治疗靶点，例如作为认知、奖励和运动。因此，靶向 mGlu 受体可能是治疗几种脑部疾病的有希望的策略。在发现 mGlu 受体的亚型选择性变构调节剂方面的持续进展，通过靶向与 mGlu 受体上的正构或内源性配体结合位点不同的位点，为大脑中单个 mGlu 受体亚型的信号传导的高度特异性调节提供了前所未有的机会。这些药剂提供了无与伦比的机会来选择性地调节与许多脑部疾病相关的神经元兴奋性、突触传递和随后的行为输出。在这里，我们回顾了支持 mGlu 受体变构调节剂作为治疗精神分裂症、物质使用障碍和压力相关疾病等神经精神疾病的新治疗方法的效用的临床前和临床证据。