Oliceridine (Olinvyk): A Comprehensive Pharmacological and Clinical Monograph on the First-in-Class G Protein-Biased Opioid Agonist

Section 1: Executive Summary

Oliceridine is a novel, synthetic, intravenously administered opioid agonist approved by the U.S. Food and Drug Administration (FDA) for the management of acute pain in adults that is severe enough to require an intravenous opioid and for whom alternative treatments are inadequate.[1] Marketed under the brand name Olinvyk, it is classified as a Schedule II controlled substance, reflecting its potential for abuse and dependence.[1] Oliceridine represents the first-in-class G protein-biased agonist at the μ-opioid receptor (MOR). This mechanism is designed to preferentially activate the G protein-coupled signaling pathway, which is primarily responsible for analgesia, while minimizing the recruitment and activation of the β-arrestin 2 pathway, a cascade implicated in many of the hallmark adverse effects of conventional opioids, including respiratory depression and gastrointestinal dysfunction.[4]

The clinical development program for oliceridine demonstrated analgesic efficacy that was superior to placebo and non-inferior to morphine in postoperative pain models following both hard tissue (bunionectomy) and soft tissue (abdominoplasty) surgeries.[7] The most pronounced clinical advantage observed in these pivotal trials was a statistically significant improvement in gastrointestinal tolerability, with patients receiving oliceridine experiencing lower rates of nausea and vomiting and requiring less rescue antiemetic medication compared to those treated with morphine at equianalgesic doses.[9]