Oliceridine

Severe acute pain occurs through nociceptive signalling involving both ascending and descending spinal pathways, in which nerve conductance is mediated in part by the action of opioid receptors.A218041, A218046 Opioid receptors are seven-transmembrane G-protein-coupled receptors (GPCRs), of which the ?-opioid receptor subtype is predominantly targeted by and is responsible for the effects of opioid agonists.A218031, A218046 However, due to the ability of some opioid agonists to bind to other targets, as well as activation of additional downstream pathways from opioid receptors such as those involving ?-arrestin, the beneficial analgesic effects of opioids are coupled with severe adverse effects such as constipation and respiratory depression.A218026, A218031, A218036, A218041, A218046

Oliceridine (formerly known as TRV130) is a "biased agonist" at the ?-opioid receptor by preferentially activating the G-protein pathway with minimal receptor phosphorylation and recruitment of ?-arrestin.A218026, A218031 By acting as a biased agonist, oliceridine provides comparable analgesia compared with traditional opioids such as morphine at a comparable or decreased risk of opioid-related adverse effects such as constipation and respiratory depression.A218026, A218031, A218051, A218056, A218061, A218066, A218071, L15516

Oliceridine was first reported in 2013,A218026, A218086 but was initially not approved by the FDA due to concerns raised by the Anesthetic and Analgesic Drug Products Advisory Committee.^A218041 Oliceridine gained FDA approval on August 7, 2020, and is currently marketed by Trevena Inc as OLINVYK™.^L15516