A novel orvinol analog, BU08028, as a safe opioid analgesic without abuse liability in primates
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 29, 2016
- Source ID
- 10.1073/pnas.1605295113
Entities
People
- Devki D. Sukhtankar
- Gerta Cami-kobeci
- Huiping Ding
- Mei-Chuan Ko
- Michael A. Nader
- Norikazu Kiguchi
- Paul W Czoty
- Stephen M. Husbands
Organizations
- National Institute on Drug Abuse
- United States Department of Defense
- University of Bath
- Wake Forest University