Recent evidence indicates that
adenosine A(2A) receptor antagonists hold therapeutic potential for the treatment of
Parkinson's disease (PD). A study on the novel
adenosine A(1) and A(2A) receptor dual antagonist 5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (
ASP5854) showed it to be effective in various rodents models of PD and cognition. In the present study, we further investigated the potential of
ASP5854 as an anti-PD
drug using
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP)-treated common marmosets, which is a highly predictive model of clinical efficacy in PD, and compared its effect with those of existing anti-PD drugs.
ASP5854 significantly and dose-dependently improved the total motor disability score for 7h at doses higher than 1mg/kg, and significantly increased total locomotor activity at doses higher than 0.1mg/kg without adverse effects. l-3,4-Dihydroxyphenylalanine+benserazide and
bromocriptine also significantly improved the motor disability score and the hypolocomotion caused by
MPTP treatment in a dose-dependent fashion. This amelioration was significant at 32+8 and 10-32 mg/kg, respectively, although
bromocriptine induced severe
emesis. Trihexiphenidyl also significantly improved the total motor disability score at doses of 10-32 mg/kg; however, while a significant increase in the total locomotor activity was observed at 10mg/kg, the
drug induced
ataxia-like behavior at 32 mg/kg. On the other hand, neither
selegiline nor
amantadine improved the total motor disability and hypolocomotion. These data substantiate the evidence that the novel
adenosine antagonist
ASP5854 exerts comparable anti-PD activity with existing anti-PD drugs, which indicates that
ASP5854 might have potential to ameliorate motor deficits in PD.