The Role and Development of the Antagonist of Adenosine A_2Ain Parkinson’s Disease

Abstract

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 A 1, A 2A , A 2B , and A 3. Adenosine A 2A 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 A 2A antagonist is also believed to have neuroprotective effects. Several compounds have been reported and have undergone clinical test as selective adenosine A 2A antagonists, including istradefylline, preladenant, tozadenant, vipadenant, ST-1535, and SYN-115. Nonselective adenosine A 2A antagonists from natural compounds are caffeine and theophylline.

Current Approaches and Tools Used in Drug Development against Parkinson’s Disease

“…In animal models, blockade of A2A receptors has been proven to alleviate motor symptoms of the disease. It is likely to have neuroprotective effects as well [ 3 , 4 ].…”

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“…The A 2A 's function in the brain involves modulating activity in the basal ganglia's indirect route. Because it colocalizes and is physically associated with various unrelated G-protein-coupled receptors, the A 2 A has complex activities 7 . Efforts to produce centrally acting treatments and reduce peripheral side effects, especially cardiac adverse effects, have long been prioritized in drug development.…”