Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease

Pharmacol Ther. 2011 Dec;132(3):280-99. doi: 10.1016/j.pharmthera.2011.07.004. Epub 2011 Jul 23.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine A2 Receptor Antagonists / pharmacology*
  • Adenosine A2 Receptor Antagonists / therapeutic use*
  • Animals
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism*
  • Receptor, Adenosine A2A / metabolism*
  • Receptors, Dopamine D2 / metabolism*


  • Adenosine A2 Receptor Antagonists
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D2