title: Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.
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 sub-effective 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.
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.affiliation: b Dipartimento di Chimica e Tecnologie del Farmaco , Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza Università di Roma , Roma , Italy.
authors.forename: Sveva
authors.initials: S
authors.lastname: Pelliccia
authors.affiliation: b Dipartimento di Chimica e Tecnologie del Farmaco , Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza Università di Roma , Roma , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Famiglini
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Azzurra
authors.initials: A
authors.lastname: Stefanucci
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Macedonio
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiavaroli
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
authors.affiliation: a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferrante
authors.affiliation: c Dipartimento del Farmaco , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieretti
authors.affiliation: d Dipartimento di Farmacia , Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Sandor
authors.initials: S
authors.lastname: Benyhe
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Zador
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Erdei
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Edina
authors.initials: E
authors.lastname: Szucs
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Reza
authors.initials: R
authors.lastname: Samavati
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Szalbolch
authors.initials: S
authors.lastname: Dvrorasko
authors.affiliation: e Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Tomboly
authors.affiliation: f Dipartimento di Chimica e Tecnologie del Farmaco , Rome Center for Molecular Design, Sapienza Università di Roma , Roma , Italy.|g Alchemical Dynamics s.r.l , Roma , Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.affiliation: f Dipartimento di Chimica e Tecnologie del Farmaco , Rome Center for Molecular Design, Sapienza Università di Roma , Roma , Italy.|g Alchemical Dynamics s.r.l , Roma , Italy.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Patsilinakos
authors.affiliation: b Dipartimento di Chimica e Tecnologie del Farmaco , Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza Università di Roma , Roma , Italy.
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D051379:Mice; D018847:Opioid Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology*; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D000077285:Rimonabant
chemical_list: D008024:Ligands; D018847:Opioid Peptides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011957:Receptors, Opioid; D000077285:Rimonabant
keywords: Cannabinoid receptor CB1R; Rimonabant; bivalent ligand; opioids; pain