Scientists Take Big Step Toward Finding Non-Addictive Painkiller

Source:  Wake Forest University Baptist Medical Center

Summary: With the support of the National Institute on Drug Abuse, scientists have been working to find a safe, non-addictive painkiller to help fight the current opioid crisis in this country.

The new chemical compound, known as AT-121 has a dual therapeutic action that suppressed the addictive effects of opioids and produced morphine-like analgesic effects in non-human primates. In the study, the team found that AT-121 to be safe and non-addictive, as well as an effective pain medication. 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. In the study, the researchers observed that AT-121 showed the same level of pain relief as an opioid, but at a 100-times lower dose than morphine. At that dose, it also blunted the addictive effects of oxycodone, a commonly abused prescription drug. The study findings were published in the journal Science Translational Medicine.

Non-addictive painkiller

Credit: Astraea Therapeutics

The main objective of this study was to design and test a chemical compound that would work on both the mu opioid receptor, the main component in the most effective prescription painkillers, and the nociceptin receptor, which opposes or blocks the abuse and dependence-related side effects of mu-targeted opioids. Current opioid pain drugs, such as fentanyl and oxycodone, work only on the mu opioid receptor, which also produces unwanted side effects – respiratory depression, abuse potential, increased sensitivity to pain and physical dependence. The bifunctional profile of AT-121 not only gave effective pain relief without abuse potential, it also lacked other opioid side-effects that patients typically struggle with, such as itch, respiratory depression, tolerance and dependence.

Prof. Mei-Chuan Ko said, “Our data shows that targeting the nociceptin opioid receptor not only dialed down the addictive and other side-effects, it provided effective pain relief”and further added, “Next steps include conducting additional preclinical studies to collect more safety data, and then if all goes well, applying to the Food and Drug Administration for approval to begin clinical trials in people.”

More Information: H. Ding et al, “A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates,” Science Translational Medicine (2018). … scitranslmed.aar3483

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