Scientists a step closer towards finding non-addictive painkiller

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Scientists from the Wake Forest School of Medicine have been working hard to come up with a safe and non-addictive pain killer that can help fight the current opioid crisis in the country – with support from the National Institute on Drug Abuse, USA. Now, they might have achieved this- though in an animal model.

The new chemical compound, called AT-121, has dual therapeutic action that can suppress the addictive effects of opioids and produce morphine-like analgesic effects in non-human primates.

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

The findings of the study were published recently in the journal Science Translational Medicine.

The research team’s principle objective was to design and test a chemical compound that would work on both the mu opioid receptor- which is the main component in the most of the effective prescribed pain killers, and also on the nociceptin receptor- which opposes or blocks the abuse and dependence-related side effects of mu-targeted opioids. The current opioid pain drugs- such as fentanyl and oxycodone, work only on the mu opioid receptor, which also causes unwanted side effects -like respiratory depression, abuse potential, increased sensitivity to pain and physical dependence.

“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 added.

Researchers also noted that AT-121 showed the same level of pain relief as an opioid does, but at a 100-times lower dose than morphine. At that dose, it also curbed the addictive effects of oxycodone- a commonly abused prescription drug.

The functional duality of AT-121 not only provided effective pain relief without abuse potential, it also didn’t cause other opioid side-effects that patients usually struggle with, such as itching, respiratory depression, tolerance and dependence.

“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 explained. “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.”

Ko says that the research team is looking to conduct additional preclinical studies to collect more safety data, and if the results are positive, eventually applying to the Food and Drug Administration for approval to begin clinical trials in people.


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