With addiction to prescription painkillers a major part of the current opioid crisis in the US, the search for an effective but non-addictive pain medication is on in earnest. And researchers at Wake Forest School of Medicine appear to have found a likely candidate in the form of a chemical compound called AT-121. With promising results seen in non-human primates, hopes are high the compound will work just as well in people.
Unlike the current most effective prescription painkillers that only work on the mu opioid receptor, such as fentanyl and oxycodone, the researchers were looking for a compound that also works on the nociception receptor, which blocks the dependence-related side effects of opioids that target the mu opioid receptor.
"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," says Mei-Chuan Ko, Ph.D., professor of physiology and pharmacology at the School of Medicine, 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 researchers say that in testing with non-human primates, AT-121 provided pain relief equivalent to an opioid, but in a 100-time lower dose than morphine. The same dose also blunted the addictive effects of oxycodone. In addition to providing pain relief without the potential for abuse, the researchers say AT-121 didn't produce other common negative side-effects commonly associated with opioids, such as itchiness, 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," says Ko. "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."
If all goes well in additional preclinical studies designed to collect more safety data, the team will apply to the FDA for approval to conduct clinical trials of the compound in people.
The team's study appears in Science Translational Medicine.
Source: Wake Forest School of Medicine
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