Indoloquinolizidine-Peptide Hybrids as Multiple Agonists for D-1 and D-2 Dopamine Receptors

Marc Vendrell*, Aroa Soriano, Vicent Casado, Jose Luis Diaz, Rodolfo Lavilla, Enric I. Canela, Carme Lluis, Rafael Franco, Fernando Albericio, Miriam Royo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 D-1 and D-2 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 D-1 and D-2 dopamine receptors and may therefore be useful for testing the therapeutic potential of multivalent drugs on these targets.

Original languageEnglish
Pages (from-to)1514-1522
Number of pages9
JournalChemMedChem
Volume4
Issue number9
DOIs
Publication statusPublished - Sep 2009

Keywords

  • combinatorial chemistry
  • GPCRs
  • indolo[2,3-a]quinolizidines
  • Parkinson's disease
  • receptors
  • PARKINSONS-DISEASE
  • ADENOSINE RECEPTORS
  • NATURAL-PRODUCTS
  • INDOLE ALKALOIDS
  • CELL-MEMBRANE
  • OXIDATION
  • DISORDERS
  • CHEMISTRY
  • AFFINITY
  • LIGANDS

Fingerprint

Dive into the research topics of 'Indoloquinolizidine-Peptide Hybrids as Multiple Agonists for D-1 and D-2 Dopamine Receptors'. Together they form a unique fingerprint.

Cite this