Researchers have discovered a new compound that aims to enhance the treatment of opioid overdoses.
Scientists at the University of Florida have identified a new compound designed to improve the treatment of opioid overdoses, which tragically claimed over 81,000 American lives last year.
The finding has the potential to address the severe epidemic of opioid-related deaths, largely driven by the widespread use of fentanyl. This highly potent synthetic opioid is commonly used for pain relief and is one of the most frequently abused substances in the country.
“Fentanyl is a major driver for the need to develop better treatments for opioid overdoses,” explained Jay McLaughlin, Ph.D., a professor of pharmacodynamics at the UF College of Pharmacy. “Each opioid-related death is preventable, underscoring the urgent need for enhanced treatment options.”
In a recent study published in the journal Nature, a collaborative team of researchers from six labs at Washington University School of Medicine in St. Louis, Stanford University, and UF describe the discovery and testing of compound 368. When used alongside the medication naloxone, compound 368 significantly increased the drug’s effectiveness in reversing the fatal effects of opioid overdoses.
Naloxone, also known as Narcan, works by blocking the effects of opioids and can temporarily reverse an opioid overdose. It serves as an antagonist by binding to opioid receptor sites on nerve cells, thereby preventing opioids like fentanyl from activating them.
Narcan can swiftly restore normal breathing in an individual whose respiration has slowed or stopped due to an opioid overdose.
“We have long understood the life-saving potential of Narcan,” McLaughlin noted. “However, Narcan’s effects are short-lived and wear off rapidly. If an individual has taken a large amount of fentanyl, they will return to respiratory distress once the Narcan wears off.”
McLaughlin further explained that Narcan can trigger withdrawal symptoms in patients dependent on opioids. The research team discovered that when compound 368 is combined with small doses of Narcan, it can reverse respiratory depression without causing withdrawal symptoms.
Both Narcan and compound 368 were found to bind to different sites on the opioid receptor, allowing them to complement each other in blocking opioids like fentanyl. This dual binding keeps Narcan attached to the receptor longer, offering prolonged protection at lower doses of the antagonist against the harmful effects of fentanyl.
“Determining the right Narcan dosage has been a persistent challenge for healthcare providers,” McLaughlin stated. “In the future, combining a smaller amount of Narcan with our compound could help avoid patients experiencing opioid withdrawal symptoms.”
This latest study builds on recent advancements in understanding the structure and function of opioid receptors, expanding on previous research published by the same team in November 2022. Their earlier work, also featured in Nature, detailed how modifications to fentanyl’s chemical structure retained its pain-relief properties while reducing negative side effects.
