title: Indoloquinolizidine-peptide hybrids as multiple agonists for D1 and D2 dopamine receptors.
abstract: Multiple-specificity ligands are considered promising pharmacological tools that may show higher efficacy in the treatment of diseases for which the modulation of a single target is therapeutically inadequate. We prepared a set of novel ligands for D1 and D2 dopamine receptors by combining two indolo[2,3-a]quinolizidine scaffolds with various tripeptide moieties. The binding and functional properties of these molecules were determined by radioligand binding studies in brain striatum membranes and by intracellular cAMP production assays in cells expressing different dopamine receptor subtypes. Some indoloquinolizidine-peptide hybrids, mainly with the trans configuration, showed dual agonist activity at both D1 and D2 dopamine receptors and may therefore be useful for testing the therapeutic potential of multivalent drugs on these targets.
authors: Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, 08028 Barcelona, Spain.
authors: Marc
authors: M
authors: Vendrell
authors: Aroa
authors: A
authors: Soriano
authors: Vicent
authors: V
authors: Casadó
authors: José Luis
authors: JL
authors: Díaz
authors: Rodolfo
authors: R
authors: Lavilla
authors: Enric I
authors: EI
authors: Canela
authors: Carme
authors: C
authors: Lluís
authors: Rafael
authors: R
authors: Franco
authors: Fernando
authors: F
authors: Albericio
authors: Miriam
authors: M
authors: Royo
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D054837:Quinolizidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism
chemical_list: D010455:Peptides; D054837:Quinolizidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2