title: 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.affiliation: CNR Institute for Neuroscience-section Cagliari, Cagliari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pinna
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002375:Catalepsy / Q000503:physiopathology; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004357:Drug Synergism; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D010300:Parkinson Disease / Q000503:physiopathology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D014316:Tritium
chemical_list: C502528:8-bromo-9-ethyladenine; C502530:8-ethoxy- 9-ethyladenine; C502529:8-furyl-9-ethyladenine; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D043705:Receptor, Adenosine A2A; D014316:Tritium; C058394:2-chloro-N(6)cyclopentyladenosine; D007980:Levodopa; D000225:Adenine; D000241:Adenosine