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Opioids remain important in postoperative analgesia although, the focus is on using them as part of multimodal regimens where it is not possible to avoid their use completely. The development of novel agents with more favorable adverse effect profiles may increase safety whilst maintaining efficacy. This article reviews the clinical trials for opioids in late-stage development. The objective of this narrative review is to evaluate the pharmacokinetic properties, safety, tolerability, and analgesic efficacy of these agents in the management of postoperative pain. Oliceridine appears to be an effective and potentially safer μ opioid receptor agonist. Its main advantages are a relatively fast onset with reduced respiratory depression, nausea, and vomiting. Cebranopadol is an agonist at multiple opioid receptors, of which μ opioid and nociceptin/orphanin FQ peptide (NOP) receptor are most significant. It is an oral drug that appears to have efficacy in neuropathic pain, with reduced respiratory depression and abuse potential. Lastly, morphine-6-glucuronide is an active metabolite of morphine with a slower onset than its parent compound. It has failed to demonstrate appreciable benefit in the context of postoperative analgesia.

Opioid MOP receptor agonists in late-stage development for the treatment of postoperative pain