Novel investigational adenosine A2A receptor antagonists for Parkinson's disease

Expert Opin Investig Drugs. 2009 Nov;18(11):1619-31. doi: 10.1517/13543780903241615.


The development of non-dopaminergic therapies for Parkinson's disease (PD) has attracted much interest in recent years. Among new classes of drugs, adenosine A(2A) antagonists have emerged as the best candidates. BIIB014, preladenant and ST-1535 are new adenosine A(2A) antagonists currently in Phase I and II clinical trials for evaluation of their efficacy in patients with PD. All these compounds have been proven safe and well tolerated. Moreover, results from Phase II trials also demonstrate that BIIB014 and preladenant are effective in reducing the waking time spent in OFF state in patients at the late stage of PD treated with L-DOPA. BIIB014 is also efficacious as monotherapy in patients at the early stage of PD. Finally, ST-1535, at this time, displays a very promising potential in experimental models of PD and a safe profile in clinical studies. This review summarizes pharmacological data available on these three A(2A) antagonists, their effects in animal models of PD and their profiles in clinical trials.

Publication types

  • Review

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenosine A2 Receptor Antagonists*
  • Animals
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacology*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Disease Models, Animal
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Triazoles / adverse effects
  • Triazoles / pharmacology


  • 2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine
  • 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-(1,2,3)triazolo(4,5-d)pyrimidine-5-amine
  • Adenosine A2 Receptor Antagonists
  • Antiparkinson Agents
  • Pyrimidines
  • Triazoles
  • 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
  • Adenine