title: Novel ergopeptides as dual ligands for adenosine and dopamine receptors.
abstract: Multivalent ligands are promising pharmacological tools that may be more efficacious for several diseases than highly selective single-target drugs. A combined therapy using dopaminergic agonists and adenosinergic antagonists is currently being evaluated for the treatment of Parkinson's disease. [(a) Kanda, T.; et al. Exp. Neurol. 2000, 162, 321-327. (b) Jenner, P. Expert Opin. Invest. Drugs 2005, 14, 729-738. (c) Kase, H.; et al. Neurology 2003, 61 (Suppl 6), S97-S100.] Here we prepared dual ligands acting on adenosine and dopamine receptors by applying a combinatorial approach based on the ergolene privileged structure. The potency and efficacy of these novel compounds were determined by radioligand binding studies and intracellular cAMP production assays in cells expressing adenosine and dopamine receptors. Selected compounds displayed dual dopamine agonist and adenosine antagonist activity. Molecules with this pharmacological profile are potentially useful for studying dopamine-adenosine cross-talk in the central nervous system and for testing the therapeutic potential of multivalent drugs for Parkinson's disease.
authors.affiliation: Combinatorial Chemistry Unit, Barcelona Science Park, Department of Biochemistry and Molecular Biology, Molecular Neurobiology Unit, IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer, IRB Barcelona, Barcelona Science Park, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Vendrell
authors.forename: Ester
authors.initials: E
authors.lastname: Angulo
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D018491:Dopamine Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004873:Ergolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D008024:Ligands; D009842:Oligopeptides; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011954:Receptors, Dopamine; D018047:Receptors, Purinergic P1; D054852:Small Molecule Libraries; D000242:Cyclic AMP