The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose of l-dopa in unilaterally 6-OHDA-lesioned rats.
Adenosine A2a antagonists can modulate dopamine-mediated motor behaviours, however, their ability to induce rotational behaviour in 6-hydroxydopamine (6-OHDA)-lesioned rats and to potentiate the effects of l-dopa differs. We now report on the effects of the novel A2a antagonist ST1535 on rotational responses in this model. When administered alone, ST1535 (2.5-40 mg/kg po) enhanced exploratory behaviour and produced a dose-related increase in ipsilateral rotation in rats with a unilateral 6-OHDA lesion of the nigro-striatal pathway. Administration of ST1535 (40 mg/kg po) in combination with a high dose of l-dopa (12 mg/kg ip) caused marked contraversive rotation but did not alter the rotational response produced by l-dopa alone. In contrast, when administered in combination with l-dopa (7 mg/kg ip) that alone produced a submaximal circling response, ST1535 enhanced the intensity and duration of rotation. These results suggest that ST1535 is able to alter dopamine-mediated behaviour when given alone and to potentiate the effects of submaximal doses of l-dopa. ST1535 may be useful in the treatment of Parkinson's disease and effective in reducing the use of l-dopa.
Rose
Sarah
S
Neurodegenerative Disease Research Centre, School of Health and Biomedical Sciences, Kings College, London SE1 1UL, UK.
Ramsay Croft
Neil
N
Jenner
Peter
P
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013565:Sympatholytics; D014230:Triazoles / Q000494:pharmacology*
C506291:2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine; D058917:Adenosine A2 Receptor Antagonists; D015259:Dopamine Agents; D043705:Receptor, Adenosine A2A; D013565:Sympatholytics; D014230:Triazoles; D007980:Levodopa; D016627:Oxidopamine; D000225:Adenine; D000241:Adenosine