A team of researchers from Washington University School of Medicine in St. Louis, Stanford University and the University of Florida discovered a new molecular compound that could increase the potency of naloxone. According to the results of the study, published in the scientific journal Nature earlier in June, the new compound is a negative allosteric modulator (NAM) of the opioid receptor, and can reverse the effects of opioids in mice at low doses without exacerbating withdrawal symptoms.
“Naloxone is a lifesaver, but it’s not a miracle drug; it has limitations,” said the study’s senior co-author Dr. Susruta Majumdar, professor of anesthesiology at Washington University in his interview with Science Daily. “Many people who overdose on opioids need more than one dose of naloxone before they are out of danger. This study is a proof of concept that we can make naloxone work better – last longer and be more potent – by giving it in combination with a molecule that influences the responses of the opioid receptor.”
Allosteric modulators are molecules that can change the body’s physiological response to drugs by modulating receptor activity. After screening a library of 4.5 billion candidate allosteric modulator molecules, they identified a molecule that significantly increased naloxone’s effectiveness in reversing opioid overdoses in mice.
We have a long way to go, but these results are really exciting,” said Dr. Jay McLaughlin, the study’s senior co-author and professor of pharmacodynamics at the University of Florida. “Opioid withdrawal likely won’t kill you, but they’re so severe that users often resume taking opioids within a day or two to stop the symptoms. The idea that we can rescue patients from overdose with reduced withdrawal might just help a lot of people.”
After the identification of several candidate NAMs, the researchers have filed a patent on them and are still working on identifying other potential candidates. According to Dr. Majdumar, a naloxone-enhancing NAM could be on the market in the next 10 to 15 years. “Developing a new drug is a very long process, and in the meantime new synthetic opioids are just going to keep on coming and getting more and more potent, which means more and more deadly,” he said. “Our hope is that by developing a NAM, we can preserve naloxone’s power to serve as an antidote, no matter what kind of opioids emerge in the future.”
