Fryc Monika, Kluzik Daria, Czopek Anna, Jończyk Jakub, Zagórska Agnieszka
Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Neuropharmacology. 2025 Nov 15;279:110622. doi: 10.1016/j.neuropharm.2025.110622. Epub 2025 Jul 31.
The serotonin 5-HT receptor is a G-protein-coupled receptor that plays a critical role in numerous physiological processes within the central nervous system. While it is essential for normal neurobiological function, dysregulation or aberrant signaling of the 5-HT receptor has been implicated in the pathophysiology of various neuropsychiatric disorders. This review provides a comprehensive overview of the 5-HT receptor, including its structure, function, ligand interactions, and therapeutic potential. Its molecular structure is detailed, with key binding domains highlighted that facilitate interactions with agonists, antagonists, and inverse agonists, influencing receptor activation and intracellular signaling pathways. The sites of 5-HT receptor expression in both the central and peripheral nervous systems are also presented, and ligands are classified based on their interactions with the receptor. The receptor's role as a focal point in the treatment of psychiatric disorders such as schizophrenia and depression is examined, with emphasis placed on its modulation by atypical antipsychotics and emerging psychedelic-based therapies. Furthermore, its involvement in functional selectivity, biased agonism, and interactions with dopaminergic and glutamatergic systems is explored. Recent advancements in non-hallucinogenic 5-HT receptor agonists and inverse agonists are also discussed, highlighting their potential for therapeutic intervention with improved safety profiles. The insights provided in this review contribute to a deeper understanding of 5-HT receptors' role in neuropsychiatric disorders and support ongoing drug development efforts to optimize receptor-targeted therapies.
血清素5-HT受体是一种G蛋白偶联受体，在中枢神经系统的众多生理过程中发挥着关键作用。虽然它对正常神经生物学功能至关重要，但5-HT受体的失调或异常信号传导与各种神经精神疾病的病理生理学有关。本综述全面概述了5-HT受体，包括其结构、功能、配体相互作用和治疗潜力。详细介绍了其分子结构，突出了关键结合域，这些结合域促进了与激动剂、拮抗剂和反向激动剂的相互作用，影响受体激活和细胞内信号通路。还介绍了5-HT受体在中枢和外周神经系统中的表达位点，并根据配体与受体的相互作用对其进行分类。研究了该受体在治疗精神分裂症和抑郁症等精神疾病中的核心作用，重点介绍了非典型抗精神病药物和新兴的基于迷幻药的疗法对其的调节作用。此外，还探讨了其在功能选择性、偏向激动作用以及与多巴胺能和谷氨酸能系统相互作用方面的参与情况。还讨论了非致幻性5-HT受体激动剂和反向激动剂的最新进展，突出了它们在改善安全性方面进行治疗干预的潜力。本综述提供的见解有助于更深入地了解5-HT受体在神经精神疾病中的作用，并支持正在进行的药物开发工作，以优化受体靶向疗法。
