Oxycodone, a semisynthetic derivative of naturally occurring thebaine, an opioid alkaloid, has been available for more than 100 years. Although thebaine cannot be used therapeutically due to the occurrence of convulsions at higher doses, it has been converted to a number of other widely used compounds that include naloxone, naltrexone, buprenorphine, and oxycodone. Despite the early identification of oxycodone, it was not until the 1990s that clinical studies began to explore its analgesic efficacy. These studies were followed by the pursuit of several preclinical studies to examine the analgesic effects and abuse liability of oxycodone in laboratory animals and the subjective effects in human volunteers. For a number of years oxycodone was at the forefront of the opioid crisis, playing a significant role in contributing to opioid misuse and abuse, with suggestions that it led to transitioning to other opioids. Several concerns were expressed as early as the 1940s that oxycodone had significant abuse potential similar to heroin and morphine. Both animal and human abuse liability studies have confirmed, and in some cases amplified, these early warnings. Despite sharing a similar structure with morphine and pharmacological actions also mediated by the μ-opioid receptor, there are several differences in the pharmacology and neurobiology of oxycodone. The data that have emerged from the many efforts to analyze the pharmacological and molecular mechanism of oxycodone have generated considerable insight into its many actions, reviewed here, which, in turn, have provided new information on opioid receptor pharmacology.

羟考酮是天然存在的蒂巴因（一种阿片类生物碱）的半合成衍生物，已有 100 多年的历史。尽管蒂巴因因高剂量时会发生惊厥而不能用于治疗，但它已被转化为许多其他广泛使用的化合物，包括纳洛酮、纳曲酮、丁丙诺啡和羟考酮。尽管羟考酮很早就被发现，但直到 20 世纪 90 年代临床研究才开始探索其镇痛功效。这些研究之后进行了几项临床前研究，以检查羟考酮对实验动物的镇痛作用和滥用倾向以及对人类志愿者的主观影响。多年来，羟考酮一直处于阿片类药物危机的最前沿，在导致阿片类药物误用和滥用方面发挥了重要作用，有人建议它导致向其他阿片类药物的过渡。早在 20 世纪 40 年代，就有人担心羟考酮具有与海洛因和吗啡类似的严重滥用潜力。动物和人类虐待倾向研究都证实了这些早期警告，并在某些情况下放大了这些警告。尽管与吗啡具有相似的结构并且药理作用也由μ-阿片受体介导，但羟考酮的药理学和神经生物学存在一些差异。从分析羟考酮药理学和分子机制的许多努力中得出的数据对其许多作用产生了相当多的见解，本文综述，这反过来又提供了阿片受体药理学的新信息。