title: Novel therapy in Parkinson's disease: adenosine A(2A) receptor antagonists.
abstract: BACKGROUND
  Parkinson's disease (PD) is a progressive neurodegenerative disorder. To date, most of the currently available therapies in PD target the dopaminergic system and none of these therapeutic approaches have been proven to modify the course of the disease. To various extents, these drugs can also cause motor and non-motor complications. A novel target, the adenosine A(2A) receptor (AA2AR), was recently identified, blockade of which may alleviate Parkinsonian symptoms, reduce motor fluctuations and potentially afford neuroprotection.
  
  
  METHODS
  This review is based on a PubMed search covering the relationship of the adenosine receptors and PD. The role of the AA2AR is reviewed and the results of preclinical investigations of antagonists are assessed. A synopsis of current drug development is provided, with a special focus on the pharmacokinetics and relevant clinical trials.
  
  
  CONCLUSIONS
  The localization of the AA2AR in the central nervous system, the ultra structural localization and the molecular mechanism of its action reveal the potential importance of the AA2AR in movement disorders. The theoretical background and experimental data indicate that AA2AR antagonists may have a potential therapeutic effect in Parkinson's disease. More importantly, the putative neuroprotective effect needs further investigation.
authors.affiliation: Albert Szent-Györgyi Clinical Center, Department of Neurology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Szabó
authors.forename: Zsigmond Tamás
authors.initials: ZT
authors.lastname: Kincses
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D011687:Purines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; 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; D004298:Dopamine