Extending this, buprenorphine, a MOR partial agonist with antagonism at KOR/DOR and weak agonism at NOP shows a ceiling effect in respiratory depression assays (Grinnell et al., 2016; Dahan et al., 2005) supporting the premise that favorable multifunctional pharmacology and MOR partial agonism may reduce undesired liabilities while synergistically optimizing analgesia. This evidence concerns the gene OPRM1 and Respiratory insufficiency due to muscle weakness.