Functionally selective (biased) mu-opiate receptor agonists approved for the management of acute pain. To be continued?

Management of severe pain is a complex and relevant issue in modern medicine. For many years, opioid analgesics, mu-opiate receptor (MOR) agonists, have been the main ones for severe pain. Effect of these drugs on MORs causes effective analgesia and various adverse drug reactions (ADRs), including life-threatening symptoms. Therefore, new MOR agonists with high analgesic potential and low ADR are necessary. G protein-coupled signaling and beta-arrestin-2 signaling pathways are or particular attention among those activated by MOR stimulation. It was suggested that analgesic effect of MOR agonists is mediated through G protein-coupled signaling pathway, while beta-arrestin-2-dependent signaling pathway mediates most ADRs. To date, two drugs (oliceridine and tegileridine) were approved in clinical practice. Their action on MOR activates predominantly G-protein-dependent signaling pathway. This new class of drugs was termed biased agonists or functionally selective receptor agonists. This article provides overview of preclinical and clinical studies conducted with representatives of these drugs (oliceridine and tegileridine). Their perspectives in real clinical practice are reviewed.