Adenosine is a neuromodulator that regulates the body’s response to dopamine and another neurotransmitter in the brain that is responsible for motoric, emotion, learning, and memory function. Adenosine is a G-protein-coupled receptor and has four subtypes, which are A1, A2A, A2B, and A3. Adenosine A2A is located in the striatum of the brain. Antagonist interferes with GABA releasing, modulates acetylcholine and releases dopamine, and also facilitates dopamine receptor’s signaling. Therefore, it can reduce motoric symptoms in Parkinson’s disease. Adenosine A2A antagonist is also believed to have neuroprotective effects. Several compounds have been reported and have undergone clinical test as selective adenosine A2A antagonists, including istradefylline, preladenant, tozadenant, vipadenant, ST-1535, and SYN-115. Nonselective adenosine A2A antagonists from natural compounds are caffeine and theophylline.