title: Current drug treatments targeting dopamine D3 receptor.
abstract: Dopamine receptors (DR) have been extensively studied, but only in recent years they became object of investigation to elucidate the specific role of different subtypes (D1R, D2R, D3R, D4R, D5R) in neural transmission and circuitry. D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D2R and D4R) differ in signal transduction, binding profile, localization in the central nervous system and physiological effects. D3R is involved in a number of pathological conditions, including schizophrenia, Parkinson's disease, addiction, anxiety, depression and glaucoma. Development of selective D3R ligands has been so far challenging, due to the high sequence identity and homology shared by D2R and D3R. As a consequence, despite a rational design of selective DR ligands has been carried out, none of currently available medicines selectively target a given D2-like receptor subtype. The availability of the D3R ligand [(11)C]-(+)-PHNO for positron emission tomography studies in animal models as well as in humans, allows researchers to estimate the expression of D3R in vivo; displacement of [(11)C]-(+)-PHNO binding by concurrent drug treatments is used to estimate the in vivo occupancy of D3R. Here we provide an overview of studies indicating D3R as a target for pharmacological therapy, and a review of market approved drugs endowed with significant affinity at D3R that are used to treat disorders where D3R plays a relevant role.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania University, Catania, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Leggio
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania University, Catania, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bucolo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania University, Catania, Italy.
authors.forename: Chiara Bianca Maria
authors.initials: CB
authors.lastname: Platania
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania University, Catania, Italy. Electronic address: salomone@unict.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Salomone
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania University, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D054333:Drug Partial Agonism; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D008024:Ligands; D050637:Receptors, Dopamine D3; D004298:Dopamine
keywords: Aripiprazole; Blonanserin; Buspirone; Cabergoline; Cariprazine; Dopamine D3 receptor