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The adenosine a2A-receptor antagonist istradefylline enhances the motor response of L-DOPA without worsening dyskinesia in MPTP-treated common marmosets
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نویسنده
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uchida s.-i. ,tashiro t. ,kawai-uchida m. ,mori a. ,jenner p. ,kanda t.
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منبع
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journal of pharmacological sciences - 2014 - دوره : 124 - شماره : 4 - صفحه:480 -485
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چکیده
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The adenosine?a2a-receptor antagonist istradefylline decreases off time in patients with parkinson's disease who are already treated with optimal doses of dopaminergic medication but can cause an increase in non-troublesome dyskinesia. preclinical experiments have shown that a 2a antagonists are most effective in potentiating motor function when combined with sub-maximal doses of l-dopa. however,the effects of combining istradefylline with sub-optimal l-dopa treatment on established dyskinesia have not been studied. we now examine the effects of acute and repeated administration of istradefylline on dyskinesia in mptp-treated common marmosets previously primed to exhibit involuntary movements by prior exposure to l-dopa. in these animals,single dose acute oral administration of istradefylline (10 mg/kg) enhanced and prolonged the anti-parkinsonian effects of a sub-optimal dose of l-dopa (2.5 mg/kg). the chronic co-administration of istradefylline (10 mg/kg) with l-dopa (2.5 mg/kg) for 21 days did not worsen the severity of existing dyskinesia. rather,the severity of dyskinesia tended to be reduced over the 21-day treatment period. these results suggest that istradefylline can be used to potentiate the effects of sub-optimal doses of l-dopa in the treatment of parkinson's disease without causing or worsening dyskinesia. © the japanese pharmacological society.
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کلیدواژه
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Anti-parkinsonian; Dyskinesia; L-DOPA; MPTP
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آدرس
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development research laboratories,research division,kyowa hakko kirin co.,ltd.,1188 shimotogari,nagaizumi-cho,sunto-gun,shizuoka 411-8731, Japan, development research laboratories,research division,kyowa hakko kirin co.,ltd.,1188 shimotogari,nagaizumi-cho,sunto-gun,shizuoka 411-8731, Japan, development research laboratories,research division,kyowa hakko kirin co.,ltd.,1188 shimotogari,nagaizumi-cho,sunto-gun,shizuoka 411-8731, Japan, strategic product portfolio department,kyowa hakko kirin co.,ltd.,tokyo 100-8185, Japan, institute of pharmaceutical sciences,school of biomedical sciences,king's college,london wc2r 2ls, United Kingdom, development research laboratories,research division,kyowa hakko kirin co.,ltd.,1188 shimotogari,nagaizumi-cho,sunto-gun,shizuoka 411-8731, Japan
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Authors
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