A novel orvinol analog, BU08028, as a safe opioid analgesic without abuse liability in primates

Abstract

Significance A potent opioid analgesic without addictive and respiratory adverse effects has been a predominant goal for opioid medicinal chemistry since the isolation of morphine from opium in the 19th century. Here we report a functional profile of a unique analog, BU08028, targeting a combination of a classical and nonclassical opioid receptors in monkeys. By examining behavioral, physiological, and pharmacologic factors, the present study demonstrates that BU08028 exhibits full antinociception and antihypersensitivity without reinforcing effects (i.e., abuse liability), respiratory depression, pruritus, adverse cardiovascular events, or acute physical dependence. Because monkey models provide the most phylogenetically appropriate evaluation of opioid receptor functions and drug effects, these findings provide a translational bridge for such ligands as effective analgesics without safety and abuse liability concerns.