title: Dopamine D3 Receptor Antagonists as Potential Therapeutics for the Treatment of Neurological Diseases.
abstract: D3 receptors represent a major focus of current drug design and development of therapeutics for dopamine-related pathological states. Their close homology with the D2 receptor subtype makes the development of D3 selective antagonists a challenging task. In this review, we explore the relevance and therapeutic utility of D3 antagonists or partial agonists endowed with multireceptor affinity profile in the field of central nervous system disorders such as schizophrenia and drug abuse. In fact, the peculiar distribution and low brain abundance of D3 receptors make them a valuable target for the development of drugs devoid of motor side effects classically elicited by D2 antagonists. Recent research efforts were devoted to the conception of chemical templates possibly endowed with a multi-target profile, especially with regards to other G-protein-coupled receptors (GPCRs). A comprehensive overview of the recent literature in the field is herein provided. In particular, the evolution of the chemical templates has been tracked, according to the growing advancements in both the structural information and the refinement of the key pharmacophoric elements. The receptor/multireceptor affinity and functional profiles for the examined compounds have been covered, together with their most significant pharmacological applications.
authors.affiliation: European Research Centre for Drug Discovery and Development and Department of Biotechnology, Chemistry and Pharmacy, University of Siena Siena, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Maramai
authors.affiliation: European Research Centre for Drug Discovery and Development and Department of Biotechnology, Chemistry and Pharmacy, University of Siena Siena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.affiliation: European Research Centre for Drug Discovery and Development and Department of Biotechnology, Chemistry and Pharmacy, University of Siena Siena, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Brogi
authors.affiliation: European Research Centre for Drug Discovery and Development and Department of Biotechnology, Chemistry and Pharmacy, University of Siena Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.affiliation: European Research Centre for Drug Discovery and Development and Department of Biotechnology, Chemistry and Pharmacy, University of Siena Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.affiliation: Institut fuer Pharmazeutische and Medizinische Chemie, Heinrich-Heine-Universitaet Duesseldorf Duesseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: European Research Centre for Drug Discovery and Development and Department of Biotechnology, Chemistry and Pharmacy, University of Siena Siena, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
keywords: GPCR; dopamine; drug optimization; multi-targeting approach; receptor antagonists; selectivity