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Limited potential of cebranopadol to produce opioid-type physical dependence in rodents.

Authors
  • Tzschentke, Thomas M1, 2
  • Kögel, Babette Y1, 2
  • Frosch, Stefanie3
  • Linz, Klaus3
  • 1 Department of Pharmacology, Grünenthal GmbH, Germany. , (Germany)
  • 2 Institute for Laboratory Animal Science, Medical Faculty, RWTH Aachen, Germany. , (Germany)
  • 3 Preclinical Drug Development, Grünenthal GmbH, Germany. , (Germany)
Type
Published Article
Journal
Addiction Biology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2018
Volume
23
Issue
5
Pages
1010–1019
Identifiers
DOI: 10.1111/adb.12550
PMID: 28944554
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cebranopadol is a novel potent analgesic agonist at the nociceptin/orphanin FQ peptide (NOP) and classical opioid receptors. As NOP receptor activation has been shown to reduce side effects related to the activation of μ-opioid peptide (MOP) receptors, the present study evaluated opioid-type physical dependence produced by cebranopadol in mice and rats. In a naloxone-precipitated withdrawal assay in mice, a regimen of seven escalating doses of cebranopadol over 2 days produced only very limited physical dependence as evidenced by very little withdrawal symptoms (jumping) even at cebranopadol doses clearly exceeding the analgesic dose range. In contrast, mice showed clear withdrawal symptoms when treated with morphine within the analgesic dose range. In the rat, spontaneous withdrawal (by cessation of drug treatment; in terms of weight loss and behavioral score) was studied after 4-week subacute administration. Naloxone-precipitated withdrawal (in terms of weight loss and behavioral score) was studied in the same groups of rats after 1-week re-administration following the spontaneous withdrawal period. In both tests, cebranopadol-treated rats showed only few signs of withdrawal, while withdrawal effects in rats treated with morphine were clearly evident. These findings demonstrate a low potential of cebranopadol to produce opioid-type physical dependence in rodents. The prospect of this promising finding into the clinical setting remains to be established. © 2017 Society for the Study of Addiction.

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