Department of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina, United States.
Am J Physiol Cell Physiol. 2023 Jul 1;325(1):C17-C28. doi: 10.1152/ajpcell.00397.2022. Epub 2023 Apr 17.
G protein-coupled receptors (GPCRs) constitute the largest family of druggable genes in the human genome. Even though perhaps 30% of approved medications target GPCRs, they interact with only a small number of them. Here, we consider whether there might be new opportunities for transformative therapeutics for neuropsychiatric disorders by specifically targeting both known and understudied GPCRs. Using psychedelic drugs that target serotonin receptors as an example, we show how recent insights into the structure, function, signaling, and cell biology of these receptors have led to potentially novel therapeutics. We next focus on the possibility that nonpsychedelic 5-HT2A receptor agonists might prove to be safe and rapidly acting antidepressants. Finally, we examine understudied and orphan GPCRs using the MRGPR family of receptors as an example.
G 蛋白偶联受体（GPCRs）是人类基因组中最大的可成药基因家族。尽管约 30%的已批准药物靶向 GPCRs，但它们仅与其中一小部分相互作用。在这里，我们考虑是否可以通过专门针对已知和研究较少的 GPCRs，为神经精神疾病提供新的变革性治疗机会。我们以靶向血清素受体的致幻药物为例，展示了这些受体的结构、功能、信号转导和细胞生物学方面的最新见解如何带来潜在的新型治疗方法。接下来，我们关注非致幻 5-HT2A 受体激动剂是否可能成为安全且快速作用的抗抑郁药的可能性。最后，我们以 MRGPR 受体家族为例，研究了研究较少和孤儿 GPCRs。
