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Antiparkinsonian Effects of Novel Adenosine A2A Receptor Antagonists

Authors

  • Anna Drabczyńska,

    1. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Krakow, Poland
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  • Małgorzata Zygmunt,

    1. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmacology, Krakow, Poland
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  • Jacek Sapa,

    1. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmacology, Krakow, Poland
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  • Barbara Filipek,

    1. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmacology, Krakow, Poland
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  • Christa E. Müller,

    1. PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany
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  • Katarzyna Kieć-Kononowicz

    Corresponding author
    1. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Krakow, Poland
    • Department of Technology and Biotechnology of Drugs, Collegium Medicum, Jagiellonian University, ul. Medyczna 9, Pl 30-688 Krakow, Poland. Fax +48(12) 6205596.
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Abstract

The present work describes the synthesis of a pyrazinopurinedione derivative which was together with a series of pyrimidopurinedione derivatives tested for potential antiparkinsonian activity in two tests: the “oxotremorine” and the “reserpine” test. For the studies compounds which had shown affinity for the adenosine A2A receptor were chosen. One compound, a pyrazinopurinedione derivative, without affinity for A2A receptors, but showing adenosine A1 receptor affinity was also investigated. The performed preliminary tests indicated that, contrary to the pyrazinopurinedione all pyrimidopurinediones demonstrated antiparkinsonian effects. As a result of present studies it may be concluded that antiparkinsonian effects of the examined compounds are correlated with the antagonistic activity toward adenosine A2A receptors in this class of compounds. However a direct correlation of the potency of both effects was not observed possibly due to different pharmacokinetic properties of the compounds. The most active derivatives of the present series were aryl-substituted pyrimidopurinediones.

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