Supported by The Mayday Fund, Scientists Take a Big Step Toward Building a Better Opioid
For the first time, scientists at the University of North Carolina School of Medicine and collaborators solved the crystal structure of the activated kappa opioid receptor bound to a morphine derivative. They then created a new drug-like compound that activates only that receptor, a key step in the development of new pain medications.
A release from the university notes that the research, published in January 2018 the journal Cell, shows a route toward creating opioids that relieve pain without causing the severe side effects at the heart of the opioid epidemic.
Currently, most opioids bind to several opioid receptors on the surface of cells, and this is one of the main reasons why opioids relieve severe pain but also trigger a wide range of side effects from nausea, numbness, and constipation to anxiety, severe dependency, hallucinations, and even death caused by respiratory depression.
The release quotes senior author Bryan Roth, MD, PhD, the Michael Hooker Distinguished Professor of Protein Therapeutics and Translational Proteomics in the Department of Pharmacology at UNC-Chapel Hill, as saying, “To create better opioids, we need to know the structure of their receptors. Until recently, this was impossible. But now we know the structure of the activated kappa opioid receptor. And we showed we can actually use the structure to make a drug-like compound with better properties than current opioids.”
The work was done in cell cultures in Roth’s lab, and in the future researchers will test this and related compounds in animal models. Also, using the detailed structure of the kappa opioid receptor (KOR), Roth’s lab and other scientists could develop other drug-like compounds highly selective for specific opioid receptors now that the structure is available...