| Autor: |
Rizzi A; Department of Medical Sciences Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara Italy., Cerlesi MC; Department of Medical Sciences Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara Italy., Ruzza C; Department of Medical Sciences Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara Italy., Malfacini D; Department of Medical Sciences Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara Italy., Ferrari F; Department of Medical Sciences Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara Italy., Bianco S; Department of Chemical and Pharmaceutical Sciences and LTTA University of Ferrara Ferrara Italy., Costa T; Department of Pharmacology Istituto Superiore di Sanita' Rome Italy., Guerrini R; Department of Chemical and Pharmaceutical Sciences and LTTA University of Ferrara Ferrara Italy., Trapella C; Department of Chemical and Pharmaceutical Sciences and LTTA University of Ferrara Ferrara Italy., Calo' G; Department of Medical Sciences Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara Italy. |
| Jazyk: |
angličtina |
| Zdroj: |
Pharmacology research & perspectives [Pharmacol Res Perspect] 2016 Aug 02; Vol. 4 (4), pp. e00247. Date of Electronic Publication: 2016 Aug 02 (Print Publication: 2016). |
| DOI: |
10.1002/prp2.247 |
| Abstrakt: |
The aim of the study was to investigate the in vitro and in vivo pharmacological profile of cebranopadol, a novel agonist for opioid and nociceptin/orphanin FQ (N/OFQ) receptors (NOP). In vitro cebranopadol was assayed in calcium mobilization studies in cells coexpressing NOP or opioid receptors and chimeric G-proteins and in a bioluminescence resonance energy transfer (BRET) assay for studying receptor interaction with G-protein and β -arrestin 2. The mouse tail withdrawal and formalin tests were used for investigating cebranopadol antinociceptive properties. In calcium mobilization studies cebranopadol showed the following rank order of potency NOP = mu > kappa ≥ delta. In BRET studies, cebranopadol promoted NOP and mu receptors interaction with G-protein with similar high potency and efficacy. However, cebranopadol did not stimulated NOP- β -arrestin 2 interactions and displayed reduced potency at mu/ β -arrestin 2. In vivo, cebranopadol exhibits highly potent and extremely long-lasting antinociceptive effects. The effects of cebranopadol in the tail withdrawal assay were sensitive to both SB-612111 and naloxone. Collectively the present results confirm and extend previous finding demonstrating that cebranopadol, by acting as mixed NOP/opioid receptor agonist, elicits robust analgesic effects in different pain models. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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