GNAI1 and Respiratory insufficiency due to muscle weakness: For example, using this approach, a MOR ligand (PZM21) with potent Gi activation and low β-arrestin recruitment (biased agonist) was identified that lacked respiratory depression and appeared to have less reinforcing effects at doses that were equi-analgesic with morphine [49] and is being explored as a strategy for the development of safer MOR opioid agonists [50].