Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments

Abstract

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 com¬pounds that include naloxone, naltrexone, buprenor-phine, 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 pre-clinical studies to examine the analgesic effects and abuse liability of oxycodone in laboratory animals and the subjective effects in human volunteers. For a num¬ber of years oxycodone was at the forefront of the opi¬oid 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 struc-ture with morphine and pharmacological actions also mediated by the i-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 mo-lecular mechanism of oxycodone have generated con-siderable insight into its many actions, reviewed here, which, in turn, have provided new information on opi-oid receptor pharmacology.