title: Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease.
abstract: Several selective antagonists for adenosine A(2A) receptors (A(2A)R) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson's disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D₂ and adenosine A(2A) receptors in the basal ganglia. At present it is believed that A(2A)R antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson's patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A(2A)R antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized antiparkinsonian drug therapy, namely the existence of (hetero)dimers/oligomers of G protein-coupled receptors, a topic that is currently the focus of intense debate within the scientific community. Dopamine D₂ receptors (D₂Rs) expressed in the striatum are known to form heteromers with A(2A) adenosine receptors. Thus, the development of heteromer-specific A(2A) receptor antagonists represents a promising strategy for the identification of more selective and safer drugs.
authors.affiliation: Laboratory of Functional Neurochemistry, Interdepartmental Research Centre for Parkinson's Disease, IRCCS National Institute of Neurology "C. Mondino", Pavia, Italy.
authors.forename: Marie Therese
authors.initials: MT
authors.lastname: Armentero
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pinna
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: José Luis
authors.initials: JL
authors.lastname: Lanciego
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2