The adenosine a2A-receptor antagonist istradefylline enhances the motor response of L-DOPA without worsening dyskinesia in MPTP-treated common marmosets

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.