Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors

Adriano Mollica, Sveva Pelliccia, Valeria Famiglini, Azzurra Stefanucci, Giorgia Macedonio, Annalisa Chiavaroli, Giustino Orlando, Luigi Brunetti, Claudio Ferrante, Stefano Pieretti, Ettore Novellino, Sandor Benyhe, Ferenc Zador, Anna Erdei, Edina Szucs, Reza Samavati, Szalbolch Dvrorasko, Csaba Tomboly, Rino Ragno, Alexandros PatsilinakosRomano Silvestri

Research output: Contribution to journalArticle

Abstract

Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at subeffective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH2. The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.

Original languageEnglish
Pages (from-to)444-451
Number of pages8
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

    Fingerprint

Keywords

  • Bivalent ligand
  • Cannabinoid receptor CB1R
  • Opioids
  • Pain
  • Rimonabant

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Mollica, A., Pelliccia, S., Famiglini, V., Stefanucci, A., Macedonio, G., Chiavaroli, A., Orlando, G., Brunetti, L., Ferrante, C., Pieretti, S., Novellino, E., Benyhe, S., Zador, F., Erdei, A., Szucs, E., Samavati, R., Dvrorasko, S., Tomboly, C., Ragno, R., ... Silvestri, R. (2017). Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 444-451. https://doi.org/10.1080/14756366.2016.1260565