Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
Mol Psychiatry. 2022 Jan;27(1):534-558. doi: 10.1038/s41380-021-01040-1. Epub 2021 Feb 15.
Traditional antidepressants largely interfere with monoaminergic transport or degradation systems, taking several weeks to have their therapeutic actions. Moreover, a large proportion of depressed patients are resistant to these therapies. Several atypical antidepressants have been developed which interact with G protein coupled receptors (GPCRs) instead, as direct targeting of receptors may achieve more efficacious and faster antidepressant actions. The focus of this review is to provide an update on how distinct GPCRs mediate antidepressant actions and discuss recent insights into how GPCRs regulate the pathophysiology of Major Depressive Disorder (MDD). We also discuss the therapeutic potential of novel GPCR targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles. Finally, we highlight recent advances in understanding GPCR pharmacology and structure, and how they may provide new avenues for drug development.
传统的抗抑郁药主要干扰单胺能转运或降解系统，需要数周时间才能发挥治疗作用。此外，很大一部分抑郁症患者对这些治疗方法有抗药性。已经开发出几种非典型的抗抑郁药，它们与 G 蛋白偶联受体 (GPCR) 相互作用，因为直接靶向受体可能会产生更有效和更快的抗抑郁作用。本综述的重点是提供最新信息，说明不同的 GPCR 如何介导抗抑郁作用，并讨论最近对 GPCR 如何调节重度抑郁症 (MDD) 病理生理学的见解。我们还讨论了新型 GPCR 靶点的治疗潜力，这些靶点因其配体选择性、表达模式或药理学特征而具有吸引力。最后，我们强调了最近在理解 GPCR 药理学和结构方面的进展，以及它们如何为药物开发提供新途径。
