Antiparkinsonian effects of novel adenosine A(2A) receptor antagonists

Arch Pharm (Weinheim). 2011 Jan;344(1):20-7. doi: 10.1002/ardp.201000124. Epub 2010 Nov 18.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists / chemical synthesis
  • Adenosine A2 Receptor Antagonists / pharmacokinetics
  • Adenosine A2 Receptor Antagonists / pharmacology*
  • Animals
  • Antiparkinson Agents / chemical synthesis
  • Antiparkinson Agents / pharmacokinetics
  • Antiparkinson Agents / pharmacology*
  • Male
  • Mice
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology
  • Purines / chemical synthesis
  • Purines / pharmacokinetics
  • Purines / pharmacology*
  • Pyrazines / chemical synthesis
  • Pyrazines / pharmacokinetics
  • Pyrazines / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Receptor, Adenosine A2A

Substances

  • Adenosine A2 Receptor Antagonists
  • Antiparkinson Agents
  • Purines
  • Pyrazines
  • Pyrimidines
  • Receptor, Adenosine A2A