title: Antiparkinsonian effects of novel adenosine A(2A) receptor antagonists.
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 A(2A) receptor were chosen. One compound, a pyrazinopurinedione derivative, without affinity for A(2A) receptors, but showing adenosine A(1) 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 A(2A) 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.
authors.affiliation: Jagiellonian University Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Drabczyńska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011687:Purines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D043705:Receptor, Adenosine A2A
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D011687:Purines; D011719:Pyrazines; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A