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Adenosine A2A Receptor Antagonists as Drugs for Symptomatic Control of Parkinson’s Disease in Preclinical Studies

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The Adenosinergic System

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 10))

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Abstract

Parkinson’s disease (PD) is primarily a neurological basal ganglia (BG)-related disorder caused by progressive degeneration of the nigrostriatal dopaminergic neurons, which results in the cardinal motor symptoms of PD, including bradykinesia (slow movement and difficulty in initiation movement), resting tremor, muscle tone rigidity, postural instability, and sensorimotor integration deficits. The gold standard of PD therapy is characterized by the dopamine precursor L-DOPA however, after several years, this therapy leads to neuropsychiatric and motor complications, including fluctuations in motor response and dyskinesias, which develop in the majority of patients. Consequently, one of the main targets of research in PD is to identify alternative therapeutic approaches to ameliorate PD symptoms without inducing motor complications. Among the non-dopaminergic strategies for PD, one of the most promising is represented by adenosine A2A receptor antagonists, due to the colocalization of these receptors and dopamine D2 receptors in the striatopallidal neurons of the BG, which provides the anatomical basis for the existence of a functional antagonistic interaction between these receptors. Thus, extensive preclinical studies have been performed to prove the effectiveness of adenosine A2A receptor blockade in counteracting the cardinal motor symptoms of PD.

This chapter describes the effects of A2A antagonists alone or in combination with L-DOPA against the cardinal motor symptoms of PD, using rodent and primate models of PD, and the main mechanisms responsible for these anti-parkinsonian effects. In addition, findings suggesting the potential utilization of A2A antagonists, as adjunctive treatments to L-DOPA to reduce the L-DOPA induced wearing-off without modifying dyskinetic movements, have been reviewed.

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Authors and Affiliations

  1. Institute of Neuroscience, National Research Council of Italy (CNR), Cagliari, Italy

    Annalisa Pinna

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  1. Annalisa Pinna
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Correspondence to Annalisa Pinna .

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Editors and Affiliations

  1. Dept. of Biomedical Sciences Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy

    Micaela Morelli

  2. Dept. of Biomedical Sciences Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy

    Nicola Simola

  3. Dept. of Neuropsychopharmacology Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

    Jadwiga Wardas

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Pinna, A. (2015). Adenosine A2A Receptor Antagonists as Drugs for Symptomatic Control of Parkinson’s Disease in Preclinical Studies. In: Morelli, M., Simola, N., Wardas, J. (eds) The Adenosinergic System. Current Topics in Neurotoxicity, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-319-20273-0_7

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