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Researchers make major stride toward developing non-addictive painkiller

A newly developed compound provides effective pain relief but lacks the addiction potential of opioids

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As the opioid epidemic rages on, scientists have been working to develop a safe, non-addictive pain medication -- and, recently, scientists made a major breakthrough toward achieving this goal.

A new chemical compound known as AT-121 appears to provide pain relief that is more powerful than morphine, but without the addictive effects of opioids.

“In our study, we found AT-121 to be safe and non-addictive, as well as an effective pain medication,” said Mei-Chuan Ko, professor of physiology and pharmacology at the School of Medicine.

“In addition, this compound also was effective at blocking abuse potential of prescription opioids, much like buprenorphine does for heroin, so we hope it could be used to treat pain and opioid abuse,” Ko said.

Cuts abuse potential

Scientists set out to design and test a chemical compound that would work on both the mu opioid receptors and the nociceptin receptors. The former is the main component in the most effective prescription pain killers, while the latter counters the abuse and dependence-related side effects of mu-targeted opioids.

Fentanyl and oxycodone, two commonly abused prescription drugs, target only the mu opioid receptors. However, researchers observed that AT-121 targets mu opioid receptors and nociceptin receptors, which enables the compound to provide pain relief while simultaneously blocking the pleasure component.

“We developed AT-121 that combines both activities in an appropriate balance in one single molecule, which we think is a better pharmaceutical strategy than to have two drugs to be used in combination,” Ko said.

Researchers observed that AT-121 provided equivalent pain relief to an opioid, but at a hundred times lower dose than morphine. The drug also did not produce other opioid side effects, such as itch, respiratory depression, tolerance, and dependence.

Dialing down addictive qualities

The new compound has been tested successfully in rats and monkeys, and final safety tests are underway before clinical trials on people can begin. When monkeys were given access to the drug, they did not seek it out or become addicted.

“Our data shows that targeting the nociceptin opioid receptor not only dialed down the addictive and other side-effects, it provided effective pain relief,” Ko said. “The fact that this data was in nonhuman primates, a closely related species to humans, was also significant because it showed that compounds, such as AT-121, have the translational potential to be a viable opioid alternative or replacement for prescription opioids.”

The new research was conducted by scientists at Wake Forest School of Medicine with the support of the National Institute on Drug Abuse. It has been published in the journal Science Translational Medicine.

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