title: Polypharmacology of dopamine receptor ligands.
abstract: Most neurological diseases have a multifactorial nature and the number of molecular mechanisms discovered as underpinning these diseases is continuously evolving. The old concept of developing selective agents for a single target does not fit with the medical need of most neurological diseases. The development of designed multiple ligands holds great promises and appears as the next step in drug development for the treatment of these multifactorial diseases. Dopamine and its five receptor subtypes are intimately involved in numerous neurological disorders. Dopamine receptor ligands display a high degree of cross interactions with many other targets including G-protein coupled receptors, transporters, enzymes and ion channels. For brain disorders like Parkinsońs disease, schizophrenia and depression the dopaminergic system, being intertwined with many other signaling systems, plays a key role in pathogenesis and therapy. The concept of designed multiple ligands and polypharmacology, which perfectly meets the therapeutic needs for these brain disorders, is herein discussed as a general ligand-based concept while focusing on dopaminergic agents and receptor subtypes in particular.
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, European Research Centre for Drug Discovery and Development, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Butini
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: K
authors.initials: K
authors.lastname: Nikolic
authors.affiliation: Heinrich Heine University Duesseldorf, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kassel
authors.affiliation: Heinrich Heine University Duesseldorf, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Brückmann
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Filipic
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Agbaba
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, European Research Centre for Drug Discovery and Development, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gemma
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, European Research Centre for Drug Discovery and Development, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Brogi
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, European Research Centre for Drug Discovery and Development, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Brindisi
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, European Research Centre for Drug Discovery and Development, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Campiani
authors.affiliation: Heinrich Heine University Duesseldorf, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany. Electronic address: stark@hhu.de.
authors.forename: H
authors.initials: H
authors.lastname: Stark
mesh_terms: D000818:Animals; D015259:Dopamine Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D064798:Polypharmacology; D011954:Receptors, Dopamine / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D011954:Receptors, Dopamine
keywords: Bivalent ligands; Designed multiple ligands; Dopamine; Drug addiction; Dual ligands; GPCR; Multi-targeting; Multifunctional ligands; Multiple targeting; Parkinson’s disease; Receptor subtypes; Schizophrenia