KF17837 - A NOVEL SELECTIVE ADENOSINE A(2A) RECEPTOR ANTAGONIST WITH ANTICATALEPTIC ACTIVITY

KF17837 is a novel selective adenosine A(2A) receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A(2A) receptor agonist, CGS 21680 (10 mu g), in a dose-dependentreceptor agonist, CGS 21680 (10 mu g), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A(2A) receptor antagonist and that the dopaminergic function odopaminergic function of the nigrostriatal pathway is potentiated by adenosine A(2A) receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.