Novel, non-addictive opioid proves safe and effective in monkeys

Researchers have identified a novel opioid drug that offers long-lasting pain relief but doesn’t cause addiction or respiratory arrest like other opioids. Results of this study, which used a primate model, were published online August 29, 2016 in 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 lead author Mei-Chuan Ko, PhD, Professor of Physiology and Pharmacology at Wake Forest Baptist Medical Center, in Winston-Salem, NC. “This is a breakthrough for opioid medicinal chemistry that we hope in the future will translate into new and safer, non-addictive pain medications.”

Currently, mu-opioid peptide (MOP) receptor agonists—including oxycodone, fentanyl, methadone, codeine, and morphine—continue to be the most widely-used analgesics in pain management, even though they are addictive and have a high mortality rate due to respiratory arrest, Dr. Ko noted.

However, recent research on the nociceptin/orphanin FQ peptide (NOP) receptor has opened the door for developing novel analgesics. Even more recently, scientists have sought to develop agonists with an affinity for both MOP and NOP receptors. Among these, BU08028 demonstrated a similar binding profile to buprenorphine (a partial MOP receptor agonist) but with better binding affinity and efficacy at NOP receptors.

For this study, Dr. Ko and colleagues tested BU08028 in 12 rhesus monkeys to determine its efficacy as an analgesic and whether it causes physical dependence. They also investigated its effects on physiological functions, including pruritus, respiration, and cardiovascular activities.

In a pain test, BU08028 produced antinociceptive effects in a dose- and time-dependent manner. In addition, 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,” Dr. Ko said.

The results also showed that BU08028 didn’t cause itching or inhibit respiratory and cardiovascular activities.

The researchers concluded that BU08028 is an effective and safe analgesic without the likelihood of abuse or other opioid-associated side effects. Further research will determine whether BU08028 itself or a related drug will be a candidate for clinical trials in humans.

“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,” Dr. Ko explained.