Schmidhammer Helmut, Spetea Mariana
Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 52a, 6020 Innsbruck, Austria.
Top Curr Chem. 2011;299:63-91. doi: 10.1007/128_2010_77.
Among opioids, morphinans play an important role as therapeutically valuable drugs. They include pain relieving agents such as naturally occurring alkaloids (e.g. morphine, codeine), semisynthetic derivatives (e.g. oxycodone, oxymorphone, buprenorphine), and synthetic analogs (e.g. levorphanol). Currently used opioid analgesics also share a number of severe side effects, limiting their clinical usefulness. The antagonist morphinans, naloxone and naltrexone are used to treat opioid overdose, opioid dependence, and alcoholism. All these opioid drugs produce their biological actions through three receptor types, mu, delta, and kappa, belonging to the G-protein-coupled receptor family. Considerable effort has been put forward to understand the appropriate use of opioid analgesics, while medicinal chemistry and opioid pharmacology have been continuously engaged in the search for safer, more efficacious and nonaddicting opioid compounds, with the final goal to reduce complications and to improve patient compliance. Toward this goal, recent advances in chemistry, ligand-based structure activity relationships and pharmacology of 14-alkoxymorphinans are reviewed in this chapter. Current developments of different structural patterns of 14-alkoxymorphinans as research tools and their potential therapeutic opportunities are also summarized.
在阿片类药物中，吗啡喃类作为具有治疗价值的药物发挥着重要作用。它们包括止痛剂，如天然存在的生物碱（如吗啡、可待因）、半合成衍生物（如羟考酮、羟吗啡酮、丁丙诺啡）以及合成类似物（如左啡诺）。目前使用的阿片类镇痛药也存在一些严重的副作用，限制了它们的临床应用。吗啡喃类拮抗剂纳洛酮和纳曲酮用于治疗阿片类药物过量、阿片类药物依赖和酒精中毒。所有这些阿片类药物都通过三种受体类型（μ、δ和κ）发挥其生物学作用，这三种受体属于G蛋白偶联受体家族。人们已经付出了相当大的努力来了解阿片类镇痛药的合理使用，同时药物化学和阿片类药物药理学一直在不断寻找更安全、更有效且无成瘾性的阿片类化合物，最终目标是减少并发症并提高患者的依从性。为了实现这一目标，本章将综述14 - 烷氧基吗啡喃类在化学、基于配体的构效关系和药理学方面的最新进展。还总结了14 - 烷氧基吗啡喃类不同结构模式作为研究工具的当前发展情况及其潜在的治疗机会。
