A2A receptor antagonists for Parkinson's disease

Adenosine A2A receptor antagonists have emerged as one of the best candidates in the ongoing search for non-dopaminergic therapies for the treatment of Parkinson’s disease. Three antagonists, BIIB014, preladenant and ST-1535, are currently in Phase I and II clinical trials for the evaluation of their efficacy in patients with Parkinson’s disease, and have proven to be safe and well tolerated. Early results from the Phase II trials of BIIB014 and preladenant show they are effective in reducing the waking time spent in off state in patients with advanced Parkinson’s disease treated with levodopa. Moreover, BIIB014 is also efficacious as monotherapy in patients in early stages of the disease. ST-1535 displays a promising potential in experimental models of Parkinson’s disease and a safe profile in clinical studies. In this review, the authors summarize pharmacological data on these three adenosine A2A antagonists, their effects in animal models and their profiles in clinical trials.