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Indoloquinolizidine–Peptide Hybrids as Multiple Agonists for D 1 and D 2 Dopamine Receptors
Author(s) -
Vendrell Marc,
Soriano Aroa,
Casadó Vicent,
Díaz José Luis,
Lavilla Rodolfo,
Canela Enric I.,
Lluís Carme,
Franco Rafael,
Albericio Fernando,
Royo Miriam
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900149
Subject(s) - receptor , dopamine , dopamine receptor , endogenous agonist , agonist , chemistry , g protein coupled receptor , tripeptide , dopamine receptor d2 , radioligand , pharmacology , peptide , biology , biochemistry , dopamine receptor d1 , neuroscience
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.