Interaction between dopamine and adenosine A2A receptors as a basis for the treatment of Parkinson's disease.
The adenosine A2A receptor antagonist SCH 58261 increases the turning behaviour induced by L-dopa in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. In this study we have evaluated the effect of a chronic intermittent administration of L-dopa or SCH 58261 plus L-dopa on turning behaviour. Chronic intermittent administration of SCH 58261 plus L-dopa produced a stable turning behaviour during the course of the treatment, whereas L-dopa alone produced a progressive increase in turning behaviour. Moreover, repeated administration of SCH 58261 failed to produce tolerance to its ability to potentiate L-dopa-induced turning behaviour. The results indicate that SCH 58261 is effective after chronic administration and suggest that SCH 58261 plus L-dopa, differently from Ldopa alone, does not produce alterations in motor responses during the course of the treatment.
Morelli
M
M
Department of Toxicology, University of Cagliari, Italy.
Pinna
A
A
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D004361:Drug Tolerance / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013565:Sympatholytics / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D013565:Sympatholytics; D014230:Triazoles; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine