title: Toward the Development of Bivalent Ligand Probes of Cannabinoid CB1 and Orexin OX1 Receptor Heterodimers.
abstract: Cannabinoid CB1 and orexin OX1 receptors have been suggested to form heterodimers and oligomers. Aimed at studying these complexes, a series of bivalent CB1 and OX1 ligands combining SR141716 and ACT-078573 pharmacophores were designed, synthesized, and tested for activity against CB1 and OX1 individually and in cell lines that coexpress both receptors. Compound 20 showed a robust enhancement in potency at both receptors when coexpressed as compared to individually expressed, suggesting possible interaction with CB1-OX1 dimers. Bivalent ligands targeting CB1-OX1 receptor dimers could be potentially useful as a tool for further exploring the roles of such heterodimers in vitro and in vivo.
authors.affiliation: Research Triangle Institute , Research Triangle Park, North Carolina 27709, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Perrey
authors.affiliation: Research Triangle Institute , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Gilmour
authors.affiliation: Research Triangle Institute , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Thomas
authors.affiliation: Research Triangle Institute , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
keywords: Cannabinoid; bivalent ligands; heterodimer; orexin