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]. Here, OPRM1 is linked to respiratory depression.