Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Biomolecules. 2022 Sep 5;12(9):1241. doi: 10.3390/biom12091241.
Despite various advantages, opioid peptides have been limited in their therapeutic uses due to the main drawbacks in metabolic stability, blood-brain barrier permeability, and bioavailability. Therefore, extensive studies have focused on overcoming the problems and optimizing the therapeutic potential. Currently, numerous peptide-based drugs are being marketed thanks to new synthetic strategies for optimizing metabolism and alternative routes of administration. This tutorial review briefly introduces the history and role of natural opioid peptides and highlights the key findings on their structure-activity relationships for the opioid receptors. It discusses details on opioid peptidomimetics applied to develop therapeutic candidates for the treatment of pain from the pharmacological and structural points of view. The main focus is the current status of various mimetic tools and the successful applications summarized in tables and figures.
尽管具有各种优势，但由于代谢稳定性、血脑屏障通透性和生物利用度方面的主要缺点，阿片肽在治疗用途方面受到限制。因此，广泛的研究集中在克服这些问题和优化治疗潜力上。目前，由于优化代谢和替代给药途径的新合成策略，许多基于肽的药物正在上市。本教程综述简要介绍了天然阿片肽的历史和作用，并重点介绍了它们对阿片受体的结构-活性关系的关键发现。它从药理学和结构的角度讨论了应用于开发治疗疼痛的治疗候选物的阿片肽类似物的细节。主要重点是各种模拟工具的现状以及以表格和图表形式总结的成功应用。
