Overview
- USF Health researchers published a Nature study on December 17 describing GTP release–selective agonists, alongside a companion mechanistic paper in Nature Communications.
- The team reports a reversible first step in mu opioid receptor signaling, where ligands can favor a 'reverse' GTP/GDP release cycle to modulate receptor activity.
- Two prototype chemicals that bias this reverse cycle enhanced morphine- and fentanyl-induced pain relief at subeffective doses without increasing respiratory suppression in preclinical models.
- The prototypes still suppress breathing at high doses and lack toxicity data, so they are not considered drug candidates at this stage.
- The NIH-funded work, which notes University of Florida patents on SR-17018 and filings for new compounds, may inform safer opioid design and could extend to other GPCRs such as the serotonin 1A receptor.