Adenosine A₂A-receptor antagonist istradefylline enhances the motor response of L-DOPA without worsening dyskinesia in MPTP-treated common marmosets.
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| Abstract |
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 A₂A 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.
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| Authors | Shin-ichi Uchida, Tomomi Tashiro, Mika Kawai-Uchida, Akihisa Mori, Peter Jenner, Tomoyuki Kanda |
| Journal | Journal of pharmacological sciences (J Pharmacol Sci) Vol. 124 Issue 4 Pg. 480-5 ( 2014) ISSN: 1347-8648 [Electronic] Japan |
| PMID | 24681641 (Publication Type: Journal Article) |
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