Cebranopadol (DB12830): A Comprehensive Monograph on a First-in-Class Dual NOP/MOP Receptor Agonist for Pain Management

Section 1: Executive Summary

Cebranopadol (DrugBank ID: DB12830) is an investigational, first-in-class, small-molecule analgesic poised to represent a significant advancement in the management of moderate-to-severe pain. Its defining characteristic is a novel mechanism of action, functioning as a potent dual agonist of the nociceptin/orphanin FQ peptide (NOP) receptor and the µ-opioid peptide (MOP) receptor.[1] This dual agonism is designed to provide potent, opioid-level analgesia while fundamentally mitigating the most severe and life-threatening side effects associated with traditional MOP receptor agonists, including respiratory depression, abuse liability, and physical dependence.[1]

Developed by Tris Pharma, Cebranopadol has demonstrated a broad spectrum of efficacy across numerous preclinical and clinical studies, showing significant pain reduction in acute postoperative pain, chronic low back pain, and painful diabetic peripheral neuropathy. The clinical development program for acute pain has culminated in the successful completion of two pivotal Phase III trials (ALLEVIATE-1 and ALLEVIATE-2), which met their primary endpoints by demonstrating statistically significant pain reduction compared to placebo. Notably, in one study, Cebranopadol showed a greater magnitude of analgesic effect than the active comparator, oxycodone.[5]

The safety profile of Cebranopadol is its most compelling feature. Clinical data indicate that it produces significantly less respiratory depression than conventional opioids.[1] Furthermore, a comprehensive series of human abuse potential studies has consistently shown that Cebranopadol has a significantly lower potential for abuse, with "drug liking" scores markedly lower than those for oxycodone, hydromorphone, and tramadol via both oral and intranasal routes of administration.[4]