Cebranopadol : a first-in-class potent analgesic agent with agonistic activity at nociceptin/orphanin FQ and opioid receptors

Pain is a syndrome of various clinical disorders, which arises from various pathological conditions and which presents significant challenges in both its diagnosis and treatment. There is currently a strong medical demand to develop new therapies with a higher efficacy and a better tolerability profile.In this review, the authors report on the available data for the pharmacological properties of cebranopadol (GRT6005), a first in-class, potent analgesic compound which acts as an agonist of nociceptin/orphanin FQ peptide (NOP) and opioid receptors. They highlight the in vitro receptor binding studies, as well as the in vivo preclinical results on the analgesic efficacy of cebranopadol obtained in several rodent pain models. The authors also briefly summarize the available data from clinical trials with cebranopadol.Cebranopadol displays analgesic, antiallodynic and antihyperalgesic properties in several rat models of acute nociceptive, inflammatory, cancer and neuropathic pain. In contrast to classical opioids, it has a higher analgesic potency in models of neuropathic pain than in acute nociceptive pain. Even at higher analgesic doses, cebranopadol does not induce motor coordination deficits or respiratory depression in rats. Hence, it seems to possess a broader therapeutic window than classical opioids. While it is particularly interesting as a novel, potent bifunctional agonist of NOP/opioid receptors, the outcome of its ongoing and planned clinical trials will be crucial for its future development and potential application in humans.