ST 1535:: A preferential A2A adenosine receptor antagonist

Antagonism of the A(2A) adenosine function has proved beneficial in the treatment of Parkinson's disease, in that it increases L-dopa therapeutical effects without concomitant worsening of its side-effects. In this paper we describe a preferential A(2A) adenosine antagonist, ST 1535, with long-lasting pharmacodynamic effects. It competitively antagonizes the effects of the A2A adenosine agonist NECA on cAMP in cells cloned with the human A(1) adenosine receptor (IC50=353 +/- 30 nM), and the effects of the A(1) adenosine agonist CHA on cAMP in cells cloned with the human A adenosine receptor (IC50=510 +/- 38 nm). ST 1535, at oral doses of 5 and 10 mg/kg, antagonizes catalepsy induced by intracerebroventricular administration of the A(2A) adenosine agonist CGS 21680 (10 mu g/5 mu l) in mice. At oral doses ranging between 5 and 20 mg/kg, ST 1535 induces hypermotility and antagonizes haloperidol-induced catalepsy in mice up to 7 h. Oral ST 1535, at 1.25 and 2.5 mg/kg, potentiates L-dopa effects in reducing haloperidol-induced catalepsy. ST 1535 represents a potential new compound, with long-lasting activity, for the treatment of Parkinson's disease.