New compound boosts naloxone’s effects

A novel compound strongly improves the efficacy of naloxone, the substance used to reverse overdoses of morphine, fentanyl and other opioid drugs . When administered to mice along with naloxone, it is 10 times as potent as naloxone alone at blocking morphine's ability to attenuate pain and depress breathing ( Nature 2024, DOI: 10.1038/s41586-024-07587-7 ). Endogenous opioids such as enkephalins and endorphins, as well as opioid drugs such as morphine and fentanyl, bind to the μ-opioid receptor . The new molecule is a type of compound called a negative allosteric modulator —negative because it dials down opioids' effects in the body and allosteric because it makes contact with a different binding site on the receptor than opioids do. "The idea of increasing or decreasing [μ-opioid] receptor activity has been around for more than a decade, but this is in my mind the first study that really has jumped to identifying