Here we investigate this hypothesis by using cell-based assays to measure human MOR-mediated G protein signaling and βarrestin2 recruitment by desmetramadol, each of its enantiomers, and clinically relevant control opioids having moderate (morphine, oxycodone) and high (fentanyl) propensity for clinical respiratory depression. Here, OPRM1 is linked to Respiratory insufficiency due to muscle weakness.