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.

Exploring the first Rimonabant analog-​opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors / Mollica, Adriano; Pelliccia, Sveva; Famiglini, Valeria; Stefanucci, Azzurra; Macedonio, Giorgia; Chiavaroli, Annalisa; Orlando, Giustino; Brunetti, Luigi; Ferrante, Claudio; Pieretti, Stefano; Novellino, Ettore; Benyhe, Sandor; Zador, Ferenc; Erdei, Anna; Szucs, Edina; Samavati, Reza; Dvrorasko, Szalbolch; Tomboly, Csaba; Ragno, Rino; Patsilinakos, Alexandros; Silvestri, Romano. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - STAMPA. - 32:1(2017), pp. 444-451. [10.1080/14756366.2016.1260565]

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

MOLLICA, Adriano;PELLICCIA, SVEVA;FAMIGLINI, VALERIA;STEFANUCCI, AZZURRA;PIERETTI, stefano;RAGNO, Rino;PATSILINAKOS, ALEXANDROS;SILVESTRI, Romano
2017

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.
File allegati a questo prodotto
File Dimensione Formato  
Mollica_Exploring_2017.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.15 MB
Formato Adobe PDF
1.15 MB Adobe PDF Visualizza/Apri PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/955362
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 24
social impact