Since the isolation of morphine from
opium in the 19th century, scientists have hoped to find a potent opioid
analgesic that isn’t addictive and doesn’t cause respiratory arrest with
Now scientists at Wake Forest Baptist Medical Center
report that in an animal model a novel pain-killing compound, BU08028, is not
addictive and does not have adverse respiratory side effects like other opioids.
The research findings are published in the Aug. 29 online edition of the
Proceedings of the National Academy of Sciences.
“Based on our research, this compound has almost zero
abuse potential and provides safe and effective pain relief,” said Mei-Chuan
Ko, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist and
lead author of the study. “This is a breakthrough for opioid medicinal
chemistry that we hope in the future will translate into new and safer, non-addictive
Pain, a symptom of numerous clinical disorders, afflicts
millions of people worldwide. Despite the remarkable advances in the
identification of novel targets as potential analgesics in the last decade,
including nociceptin-orphanin FQ peptide (NOP) receptor, mu opioid peptide
(MOP) receptor agonists remain the most widely used drugs for pain management
even though they are addictive and have a high mortality rate caused by
respiratory arrest, Ko said.
This study, which was conducted in 12 non-human primates,
targeted a combination of classical (MOP) and non-classical (NOP) opioid
receptors. The researchers examined behavioral, physiological and pharmacologic
factors and demonstrated that BU08028 blocked the detection of pain without the
side effects of respiratory depression, itching or adverse cardiovascular events.
In addition, the study showed pain relief lasted up to 30
hours and repeated administration did not cause physical dependence.
“To our knowledge, this is the only opioid-related
analgesic with such a long duration of action in non-human primates,” Ko said. “We
will investigate whether other NOP/Mop receptor-related compounds have similar
safety and tolerability profiles like BU08028, and initiate investigational new
drug-enabling studies for one of the compounds for FDA’s approval.”
This study was supported by the National Institutes of
Health, National Institute on Drug Abuse, grants DA023281, DA032568 and DA035359,
and the U.S. Department of Defense contract W81XWH-13-2-0045.
Co-authors are: Huiping Ding, Ph.D., Paul W. Czoty,
Ph.D., Norikazu Kiguchi, Ph.D., Devki D. Sukhtankar, Ph.D., Michael A. Nader, Ph.D.,
of Wake Forest Baptist; and Gerta Cami-Kobeci, Ph.D., and Stephen M. Husbands, Ph.D., of the University
of Bath, United Kingdom.