Benefit and Risk Evaluation of Biased μ-Receptor Agonist Oliceridine versus Morphine

ConclusionsThese data indicate a favorable oliceridine safety profile over morphine when considering analgesia and respiratory depression over the clinical concentration range.Editor ’s PerspectiveWhat We Already Know about This TopicClassical opioid analgesics engage two distinct transduction pathways after μ-opioid receptor activation, the G-protein–coupled signaling pathway and the β-arrestin pathwayThe G-protein pathway is primarily involved in analgesia, reward, and liking, while the β-arrestin pathway is involved in adverse effects such as respiratory depressionOliceridine is a μ-opioid receptor agonist that selectively engages the G-protein–coupled signaling pathway with reduced activation of the β-arrestin pathwayWhat This Article Tells Us That Is NewUtility functions were developed from population pharmacokinetic –pharmacodynamic analyses of oliceridine and morphine concentration–effect relationships in 29 healthy male volunteersThe utility function was defined as the probability of providing analgesia, an increase in hand withdrawal latency of 50% or more, minus the probability of producing respiratory depression, a decrease of the ventilatory response to hypercapnia of at least 25%Over the clinically relevant concentration range, oliceridine had a higher probability of providing analgesia than producing respiratory depression, while morphine had a higher probability of producing respiratory depression than providing analgesia

Source: Anesthesiology - July 1, 2020 Category: Anesthesiology Source Type: research