The Dopamine D2 and Adenosine A2A Receptors: Past, Present and Future Trends for the Treatment of Parkinson's Disease
M. Jorg, P.J. Scammells and B. Capuano
Affiliation: Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Keywords: Adenosine A2A receptor antagonist, bivalent ligand, dopamine, dopamine D2 receptor agonist, G protein-coupled
receptor, levodopa, non-dopaminergic drug, Parkinson’s disease.
Herein, we present an overview of the historic development of drugs for the treatment of Parkinson’s disease as
well as prospective novel treatment forms based on targeting the dopamine and adenosine receptors. The review includes
the development of levodopa, a precursor of the neurotransmitter dopamine, which to date is the most commonly
prescribed and most effective drug for controlling the motor symptoms of Parkinson's disease, to more recent studies of
the adenosine receptor; a promising target for the treatment of Parkinson’s disease due to its intrinsic neuroprotective
nature. Ongoing and future drug-based research on the dopamine and adenosine receptors has the advantage of being
guided by the improved understanding of receptor topography as well as their functional roles. Breakthroughs such as the
first ligand-bound X-ray structure of a selective adenosine A2A receptor antagonist in complex with the adenosine A2A
receptor, the discovery of the existence of dopamine D2 homodimers, dopamine D2- adenosine A2A heterodimers and
higher order oligomers in addition to technological progress have changed the direction of research in academia and
industry and form the pillars for novel and exciting discoveries in this field.
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