New adenosine A2A receptor antagonists: actions on Parkinson's disease models.

Abstract

The 8-substituted 9-ethyladenine derivatives: 8-bromo-9-ethyladenine (ANR 82), 8-ethoxy- 9-ethyladenine (ANR 94), and 8-furyl-9-ethyladenine (ANR 152) have been characterized in vitro as adenosine receptor antagonists. Adenosine is deeply involved in the control of motor behaviour and substantial evidences indicate that adenosine A(2A) receptor antagonists improve motor deficits in animal models of Parkinson's disease. On this basis, the efficacy of ANR 82, ANR 94, and ANR 152 in rat models of Parkinson's disease was evaluated. All compounds tested reversed the catalepsy induced by haloperidol. However, in unilaterally 6-hydroxydopamine-lesioned rats, only ANR 94 and ANR 152 potentiated l-dihydroxy-phenylalanine (l-DOPA) effect on turning behaviour and induced contralateral turning behaviour in rats sensitised to l-DOPA. Taken together the results of this study indicate that some 8-substituted 9-ethyladenine derivatives ameliorate motor deficits in rat models of Parkinson's disease, suggesting a potential therapeutic role of these compounds.

• Authors: Annalisa Pinna, Rosaria Volpini, Gloria Cristalli, Micaela Morelli
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 512 Issue 2-3 Pg. 157-64 (Apr 11 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15840400 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 8-bromo-9-ethyladenine
• 8-ethoxy- 9-ethyladenine
• 8-furyl-9-ethyladenine
• Adenosine A2 Receptor Antagonists
• Antiparkinson Agents
• Receptor, Adenosine A2A
• Tritium
• 2-chloro-N(6)cyclopentyladenosine
• Levodopa
• Adenine
• Adenosine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Adenosine (analogs & derivatives, metabolism)
• Adenosine A2 Receptor Antagonists
• Animals
• Antiparkinson Agents (pharmacology)
• Behavior, Animal (drug effects)
• Binding, Competitive (drug effects)
• CHO Cells
• Catalepsy (physiopathology)
• Cricetinae
• Cricetulus
• Disease Models, Animal
• Drug Synergism
• Levodopa (pharmacology)
• Male
• Molecular Structure
• Parkinson Disease (physiopathology)
• Radioligand Assay
• Rats
• Rats, Sprague-Dawley
• Receptor, Adenosine A2A (genetics, metabolism)
• Tritium