Cebranopadol

Cebranopadol is an analgesic of the benzenoid class which is currently under development for the treatment of pain. It is currently under development by Tris Pharma, was originally discovered and developed by Grünenthal, and was formerly developed by Park Therapeutics and Depomed. As of August 2025, the drug has reached phase 3 clinical trials. Cebranopadol either has been encountered or could be encountered as an opioid designer drug.

Pharmacology

Cebranopadol is unique in its mechanism of action via acting as a full agonist of the μ-opioid receptor and nociceptin receptor . It has lower affinity for the δ-opioid receptor, and is a partial agonist of the κ-opioid receptor. The Effective [dose (pharmacology)|EC₅₀] values of 0.5–5.6 μg/kg when introduced intravenously and 25.1 μg/kg after oral administration.
Cebranopadol shows antinociceptive and antihypertensive effects in a variety of different animal models of pain. It has also been found to be more effective in models of chronic neuropathic pain than acute nociceptive pain compared to selective μ-opioid receptor agonists. Relative to morphine, tolerance to the analgesic effects of cebranopadol has been found to be delayed. In addition, unlike morphine, cebranopadol has not been found to affect motor coordination or reduce respiration in animals at doses in or over the dosage range for analgesia. As such, it might have improved and prolonged efficacy and greater tolerability in comparison to existing opioid analgesics.
As an agonist of the κ-opioid receptor, cebranopadol may have the capacity to produce psychotomimetic effects, dysphoria, and other adverse reactions at sufficiently high doses, a property which could potentially limit its practical clinical dosage range, but would likely reduce the occurrence of patients taking more than their prescribed dose.