Oliceridine - Breakthrough in the Management of Pain

Oliceridine an intravenous opioid approved in 2020 by the Food and Drug Administration (FDA) to treat moderate-to-severe pain. Oliceridin developed with a novel mechanism that is biased agonism toward G-protein-coupled receptors pathway. Being biased agonist, it does not activate beta arrestin pathway responsible for opioid-related adverse events (ORAE), especially respiratory depression. Because of the novel mechanism, oliceridine has paved a pathway to decrease ORAE. Oliceridine has received breakthrough status by FDA. However, FDA denied oliceridine approval and withdrew breakthrough status by 2019. FDA made this decision because of the inadequacy of the safety data. Abuse potential and QT prolongation studies are conducted as per FDA recommendation in the year 2019; oliceridine was approved for moderate to severe pain in adults. This review will briefly summarize the pharmacological properties and study results of oliceridine in the management of pain. Thorough literature search was done for the efficacy and safety of oliceridine, search was done in electronic database of PubMed and Cochrane from inception till June 2021. Oliceridine was found to be effective in acute severe pain with less OREA when compared to morphine. Oliceridine has many drawbacks than what is hypothesized earlier, but this approach has opened new options for patients suffering from severe pain. Long?term effect of oliceridine has to be monitored to assess the effects of biased agonism.

Can oliceridine (TRV130), an ideal novel µ receptor G protein pathway selective (µ-GPS) modulator, provide analgesia without opioid-related adverse reactions?

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to µ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the β-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the β-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the µ receptor G protein pathway selective (µ-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased µ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.