Opioids are a class of powerful pain-relieving drugs that work by activating opioid receptors on nerve cells in the body and brain. These pain relievers are generally safe when taken for a short time and as prescribed by a doctor, but are frequently misused because they also produce euphoria. When misused or abused, opioid pain relievers can be addictive and dangerous.
Scientists have identified 3 types of opioid receptors: mu, delta, and kappa. The mu receptors are responsible for opioids’ pleasurable effects and ability to relieve pain. Studies suggest that once activated, the mu receptor turns on 2 signaling pathways. One pathway, mediated by the G protein Gi, underlies opioids’ pain-relieving properties. The other, mediated by the beta-arrestin protein, leads to the undesirable side effects of opioids, such as constipation and slowed breathing.
To search for a potential pain reliever with fewer side effects than current opioids, a research team led by Dr. Bryan Roth at the University of North Carolina and Dr. Brian Shoichet at the University of California, San Francisco, screened more than 3 million compounds for those that may be able to turn on the Gi-mediated pathway, but not beta-arrestin. The study was funded by NIH’s National Institute of General Medical Sciences (NIGMS), National Institute on Drug Abuse (NIDA), and National Institute of Mental Health (NIMH). The findings were reported online in Nature on August 17, 2016.