title: Cebranopadol: novel dual opioid/NOP receptor agonist analgesic.
abstract: OBJECTIVE
  Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol.
  
  
  METHODS
  Published literature and Internet sources were searched to identify information related to the basic science (pharmacology and medicinal chemistry) and development (clinical trial) information on the mechanism of dual opioid and NOP receptor pharmacologic action in general, and for cebranopadol in particular. The identified sources were reviewed and the information synthesized.
  
  
  RESULTS
  The preclinical testing of cebranopadol has characterized it as a dual opioid and NOP receptor agonist that displays antinociceptive and antihyperalgesic action in a variety of acute and chronic pain models in animals. Unlike most current traditional opioids, it is generally more potent against neuropathic than nociceptive pain. Several phase 2 clinical trials have been completed.
  
  
  CONCLUSIONS
  Despite the medical need, a truly novel centrally acting analgesic has not been developed in many years. Cebranopadol represents a truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits the results of phase 3 clinical trials.
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.|University of Arizona College of Pharmacy, Tucson, AZ, USA.
authors: R B
authors: RB
authors: Raffa
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: G
authors: G
authors: Burdge
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: J
authors: J
authors: Gambrah
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: H E
authors: HE
authors: Kinecki
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: F
authors: F
authors: Lin
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: B
authors: B
authors: Lu
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: J T
authors: JT
authors: Nguyen
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: V
authors: V
authors: Phan
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: A
authors: A
authors: Ruan
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: M A
authors: MA
authors: Sesay
authors: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: T N
authors: TN
authors: Watkins
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D011957:Receptors, Opioid / Q000819:agonists*; D013141:Spiro Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D000094942:Nociceptin Receptor
chemical_list: C000589289:6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine; D000700:Analgesics; D007211:Indoles; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human
keywords: analgesic; cebranopadol; chronic pain; nociceptin/orphanin FQ; opioid