Istradefylline (ISD) is a new drug developed for the treatment of Parkinson's 
disease (PD). It is an adenosine receptor A2A antagonists that will represent an 
important option for patients with advanced PD where it has been demonstrated 
efficacy in decreasing daily OFF time and is well tolerated. ISD has been 
marketed in Japan since May 2013. Areas covered: The objective of this review is 
to summarize evidences emerged from clinical studies that have demonstrated the 
efficacy of ISD in advanced parkinsonian patients. It will then focus on the 
potential role in treating non-motor symptoms (NMS) and cognitive decline, which 
heavily affect quality of life for PD patients. Its putative role as 
neuroprotective agent will also be discussed. Expert opinion: ISD might 
represent an alternative option for patients with advanced PD. The reduction of 
OFF time highlighted in pivotal trials is comparable to that obtained with 
different levodopa adjunct therapies. The low profile of side effects makes ISD 
a more suitable drug for advanced patients whose illness is complicated by 
depression or cognitive impairment. Future studies are warranted to investigate 
the possible effects of this drug to delay the occurrence of dyskinesia and to 
impact significantly on NMS.