The efficacy of oral adenosine A_2A antagonist istradefylline for the treatment of moderate to severe Parkinson's disease

The moderate and severe stages of Parkinson's disease (PD) are marked by motor and non-motor complications that still remain difficult to control with the currently available therapy. Adenosine A_2A receptor antagonists target non-dopaminergic systems, and have emerged as promising add-on therapy in the management of PD, a little more than a decade ago. While the development of this new drug class was slower than initially expected, istradefylline was recently registered in Japan, because it provides reduction of the off-time, when given in association with levodopa. Effects on some non-motor features have also been suggested, and preliminary studies further suggest a potential neuroprotective effect. Associations of A_2A receptor antagonists with dopaminergic agents, as well as enzyme blockers like catechol-O-methyltransferase (COMT) and monoamine oxidase-B (MAO-B) inhibitors, should provide even greater benefit in advanced PD patients, and, thus, a more individualized treatment approach would be at hand.