Wiśniewski Kazimierz
Ferring Research Institute Inc., San Diego, CA, USA.
Methods Mol Biol. 2019;2001:235-271. doi: 10.1007/978-1-4939-9504-2_11.
The neurohypophyseal hormone oxytocin (OT) and related modulators of the oxytocin receptor (OTR) have been the subject of intensive research for nearly seven decades. Despite having rather poor drug-like properties, OT is used as a treatment for labor induction, postpartum hemorrhage, and lactation support. The potential use of OT in the treatment of central nervous system (CNS)-related diseases has recently renewed interest in the pharmacology of OT. Oxytocin is one of the most extensively studied cyclic peptides and since the elucidation of its structure in 1953 thousands of peptidic OT analogs with antagonistic and agonistic properties have been synthesized and biologically evaluated. Among them are atosiban, a mixed oxytocin receptor (OTR)/vasopressin 1a receptor (VR) antagonist used as a tocolytic agent approved (in certain countries), and carbetocin, a longer acting OTR agonist on the market for the treatment of postpartum hemorrhage. Many other OT analogs with improved pharmacological properties (e.g., barusiban, Antag III) have been identified. These peptides have been tested in clinical trials and/or used as pharmacological tools. In this chapter, the modifications of the OT molecule that led to the discovery of these compounds are reviewed.
神经垂体激素催产素（OT）及其催产素受体（OTR）的相关调节剂已成为近七十年来深入研究的对象。尽管OT的类药物性质相当差，但它仍被用于引产、产后出血和促进泌乳。OT在治疗中枢神经系统（CNS）相关疾病方面的潜在用途最近重新引发了人们对OT药理学的兴趣。催产素是研究最为广泛的环肽之一，自1953年其结构被阐明以来，已合成了数千种具有拮抗和激动特性的肽类OT类似物，并进行了生物学评估。其中包括阿托西班，一种混合性催产素受体（OTR）/血管加压素1a受体（VR）拮抗剂，在某些国家被批准用作宫缩抑制剂；还有卡贝缩宫素，一种长效OTR激动剂，用于治疗产后出血。还发现了许多其他具有改善药理学性质的OT类似物（如巴芦西班、拮抗剂III）。这些肽已在临床试验中进行了测试和/或用作药理学工具。在本章中，将对导致这些化合物被发现的OT分子修饰进行综述。
