USF Health researchers have discovered a new way opioid receptors work that may lead to safer painkillers. Their study, titled "GTP release-selective agonists prolong opioid analgesic efficacy," shows that certain experimental compounds enhance pain relief without increasing dangerous side effects such as depressed breathing. These compounds promote the reverse reaction in the first step of the opioid receptor chain reaction instead of the forward one. According to Dr. Bohn's two new chemicals in low doses enhance the analgesic effect of morphine and fentanyl, but do not affect respiratory suppression. These prototype molecules are not drug candidates because they suppress respiration at high doses and have not been tested for toxicity. The research provides a framework for developing new opioids that last longer, work better and pose fewer risks. The study also opens up possibilities for safer treatment of other brain disorders. In 2024, 68 percent of all overdose deaths were caused by opioids, with 88 percent from fentanyl and other synthetic opioids.