Scientists may be one step closer toward more effective treatments for opioid overdose after a new compound was discovered to improve the success rates of existing treatments.
America has been in the grips of an opioid epidemic, causing more than 80,000 U.S. deaths in 2022 alone, according to the Centers for Disease Control and Prevention (CDC). These drugs attach to so-called opioid receptors in the brain that are involved in regulating pain and emotion.
Opioids can be derived from the opium poppy plant, but others are made entirely in the laboratory. These so-called synthetic opioids have become the leading cause of opioid-related deaths in the U.S, with fentanyl topping the list as the most prevalent and significant opioid threat to the United States. While fentanyl is produced legally for controlled pain relief and anesthetics, the drug is often diverted via theft, fraudulent prescriptions and illicit distribution, according to the Drug Enforcement Administration.
Earlier this year, the Food and Drug Administration (FDA) approved an over-the-counter nasal spray that can reverse the effects of opioid overdoses. The compound, called naloxone, works by attaching to the opioid receptors in our brains. Their affinity with these receptors is so strong that they are able to knock other opioids off, reversing the effects of the overdose. However, the compound only works in the body for 30 to 90 minutes, and many opioid drugs can persist beyond this efficacy window.
"Naloxone is typically an excellent opioid overdose prevention treatment," Evan O'Brien and Susruta Majumdar, from the Department of Molecular and Cellular Physiology at Stanford University's School of Medicine, told Newsweek. "In certain cases of large overdoses of potent opioids (e.g. fentanyl), naloxone doses will wear off and be eliminated by the body before the fentanyl is out of the system, causing further overdoses. Naloxone is typically packaged in 2-dose regimens for this reason."
But what if we could boost naloxone by making it bind even more strongly with the opioid receptors?
For years, scientists have been working to find molecules that are able to increase the affinity of Naloxone for these opioid receptors. But so far, promising drug candidates have been hard to pin down.
Now, the Stanford team has identified a potential compound, named "368," which selectively binds to the opioid receptors and enhances their affinity with naloxone boosting the latter's potency by more than sevenfold. Not only has compound 368 demonstrated its ability to work cooperatively with naloxone to block the effects of various opioid drugs, but it also lowers the doses of naloxone required to produce these lifesaving effects.
"This is at the early discovery stage; this is a new class of compounds that have not been characterized before," the researchers said.
"The molecule (or related compounds) needs to be further optimized for enhancing its druglike properties like potency and duration of action before continued preclinical experiments to optimize its co-administration with naloxone. [However,] we hope this molecule, or related compounds, may serve in the future as additional tools in the fight against opioid overdose deaths."
They added that more work also needs to focus on upstream problems, including the development of less addictive pain-relief treatments, as well as better treatments for opioid-use disorders.
Their findings were published in the journal Nature on July 3.
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About the writer
Pandora Dewan is a Senior Science Reporter at Newsweek based in London, UK. Her focus is reporting on science, health ... Read more
