Adenosine A2A receptor antagonists represent a new way forward in the 
symptomatic treatment of Parkinson's disease (PD) through a non-dopaminergic 
mechanism. As a class, adenosine A2A antagonists are effective in reversing 
motor deficits in haloperidol-treated rodents, 6-OHDA-lesioned rats, and 
MPTP-treated primates when combined with low doses of l-dopa or dopamine agonist 
drugs. Importantly, they improve motor function without worsening dyskinesia and 
they may prevent the onset of involuntary movements. Adenosine A2A receptor 
antagonists are active in animal models of reduced cognition, anxiety, and 
depression and so this drug class may also be effective in controlling the 
neuropsychiatric components of nonmotor symptoms in PD. Preclinical evidence has 
shown that A2A antagonists can prevent neuronal loss in experimental models of 
PD and their disease modifying activity needs to be explored in man. 
Importantly, a number of A2A antagonists have been studied in PD in clinical 
trial for their effects on motor function. So far, little evidence has emerged 
of an effect of monotherapy with adenosine antagonists in early PD. However, in 
later stage, patient populations already treated with dopaminergic drugs but 
exhibiting "wearing off," adenosine antagonists have been demonstrated to reduce 
"off" time without increasing troublesome dyskinesia in phase IIB trials. 
However, in larger phase III evaluations, a consistent significant decrease in 
"off" time has proved more difficult to demonstrate-due in part to trial 
conduct. So far, only istradefylline has completed phase III development and it 
is now marketed for the treatment of PD. Adenosine A2A antagonists are the first 
non-dopaminergic approach to the treatment of PD to appear in the recent era. 
They represent a novel way of approaching therapy that will provide additional 
benefit to that achieved with dopaminergic medication, while avoiding common 
side effects and may in addition, improve some nonmotor symptoms of PD that are 
currently poorly treated.