title: An update on adenosine A2A receptors as drug target in Parkinson's disease.
abstract: Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A(2A) receptors (A(2A)Rs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D(2) receptor (D(2)R). Furthermore, it is assumed that the formation of balanced A(2A)R/D(2)R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A(2A)R activation reduces the affinity of striatal D(2)R for dopamine and the blockade of A(2A)R with specific antagonists facilitates function of the D(2)R. Thus, it may be postulated that A(2A)R antagonists are pro-dopaminergic agents. Therefore, A(2A)R antagonists will potentially reduce the effects associated with dopamine depletion in Parkinson's disease (PD). Accordingly, this class of compounds have recently attracted considerable attention as potential therapeutic agents for PD pharmacotherapy as they have shown potential effectiveness in counteracting motor dysfunctions and also displayed neuroprotective and anti-inflammatory effects in animal models of PD. Overall, we provide here an update of the current state of the art of these A(2A)R-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.
authors.affiliation: Servei de Farmacologia Clínica, Hospital Universitari de Bellvitge-ICS, IDIBELL, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Vallano
authors.forename: Victor
authors.initials: V
authors.lastname: Fernandez-Duenas
authors.forename: Consuelo
authors.initials: C
authors.lastname: Pedros
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Arnau
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D011687:Purines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D043705:Receptor, Adenosine A2A / Q000378:metabolism* / Q000502:physiology; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011687:Purines; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C111599:istradefylline; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine