Summary of A New Approach to Pain Relief Without Addiction:
Researchers at Washington University School of Medicine in St. Louis have identified a potential new approach to pain relief without triggering addiction or hallucinations. The current pain-relieving drugs, such as morphine and oxycodone, target the mu-opioid receptor, which leads to addiction, while alternative drugs targeting the kappa opioid receptor can cause hallucinations. However, by identifying specific binding sites on the kappa receptor that don’t lead to hallucinations and understanding the interaction of the G proteins linked to the receptor, the researchers believe it may be possible to develop drugs that only activate pain-relief pathways without triggering hallucinations or addiction.
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A new approach to developing painkillers identified
Scientists at Washington University School of Medicine in St. Louis have identified a new approach to developing painkillers that do not cause addiction or hallucinations. Currently, pain-relieving drugs like morphine and oxycodone target the mu-opioid receptor, which can lead to addiction, while alternative medicines that target the kappa opioid receptor can cause hallucinations. Researchers found that specific binding sites on the kappa receptor do not lead to hallucinations. By understanding how the seven G proteins linked to the receptor interact, they believe it may be possible to develop drugs that only activate pain-relief pathways without triggering hallucinations or addiction.
Strategies to treat pain without triggering addiction or hallucinations are elusive. Scientists have attempted to develop drugs that selectively activate one type of opioid receptor to treat pain while not starting a different kind of opioid receptor linked to addiction. Unfortunately, those compounds can cause a different unwanted effect: hallucinations. But a new study has identified a potential route to pain relief that neither triggers addiction nor activates the pathway that causes hallucinations.
Opioid drugs that interact with the mu-opioid receptor have led to the current opioid epidemic, causing more than 100,000 overdose deaths in the U.S. in 2021. Developing new drugs to target other kappa receptor binding sites may relieve pain without the addictive problems associated with older opioids or the hallucinations associated with existing drugs that selectively target the kappa opioid receptor. Targeting the kappa receptor to block pain without hallucinations would be an essential step forward, according to principal investigator Tao Che.
Researchers identify potential mechanisms for hallucinations.
Researchers at the Center for Clinical Pharmacology at Washington University School of Medicine and the University of Health Sciences have identified the potential mechanisms behind hallucinations associated with drugs that selectively target the kappa opioid receptor. Using electron microscopes, they have determined how a natural compound related to the salvia plant selectively binds only to the kappa receptor, causing hallucinations.
“Since 2002, scientists have been trying to learn how this small molecule causes hallucinations through kappa receptors,” said principal investigator Tao Che. “We determined how it binds to the receptor and activates potential hallucinogenic pathways, but we also found that other binding sites on the kappa receptor don’t lead to hallucinations.”
Researchers have found a way to activate the kappa receptor without causing hallucinations.
Researchers at the Center for Clinical Pharmacology at Washington University School of Medicine and the University of Health Sciences have found that different G proteins linked to the kappa receptor can activate beneficial effects while avoiding side effects such as hallucinations. There are seven G proteins related to the kappa receptor, and their differences may help explain why some compounds cause side effects such as hallucinations.
“All of these proteins are similar, but the specific protein subtypes that bind to the kappa receptor determine which pathways will be activated,” Che said. “We have found that the hallucinogenic drugs can preferentially activate one specific G protein but not others, suggesting that beneficial effects such as pain relief can be separated from side effects such as hallucinations. So we expect it will be possible to find therapeutics that activate the kappa receptor to kill pain without activating the specific pathway that causes hallucinations.”
Conclusion
The identified approach to developing painkillers that do not cause addiction or hallucinations shows promise for addressing the opioid epidemic and safely treating pain. By understanding how specific binding sites on the kappa receptor do not lead to hallucinations and identifying different G proteins linked to the receptor, researchers may be able to develop safer pain-relieving drugs. These drugs could potentially activate pain-relief pathways without triggering addiction or hallucinations.
