Adenosine A_2A antagonists and Parkinson's disease

Although there is no cure for Parkinson's disease (PD), there are several classes of medications with various mechanisms of action that can help improve the functionality of someone with PD. Dopamine derivatives are first line therapies for PD, hence dopamine receptor agonists (DAs) have been shown to improve functionality of symptoms in PD patients. The two main formulations of dopamine agonist medications in PD therapy are ergoline and non-ergoline derivatives. Additionally, it has been shown that PD can involve irregularities in other neurotransmitters, such as acetylcholine, norepinephrine, and serotonin, hence why non-dopaminergic medications are also vital in PD management. Examples include NMDA receptor antagonists, dopamine antagonists (i.e. neuroleptics), acetylcholine receptor antagonists, serotonin receptor 2A agonists, and adenosine A₂ antagonists. In general, dopaminergic medications are the most effective in improving motor involvement with PD, whereas non-dopaminergic medications tend to focus on the non-motor involvement of PD. In this chapter, we will focus on the chemistry and medication background on dopaminergic vs non-dopaminergic therapy, with a focus of adenosine A₂ antagonists at the end.