title: ST 1535: a preferential A2A adenosine receptor antagonist.
abstract: Antagonism of the A2A 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 A2A 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 A2A adenosine receptor (IC50=353+/-30 nM), and the effects of the A1 adenosine agonist CHA on cAMP in cells cloned with the human A1 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 A2A adenosine agonist CGS 21680 (10 microg/5 microl) 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.
authors.affiliation: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Pomezia (Rome), Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Stasi
authors.forename: Franco
authors.initials: F
authors.lastname: Borsini
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Di Cesare
authors.forename: Patrizia
authors.initials: P
authors.lastname: Minetti
authors.forename: Orlando
authors.initials: O
authors.lastname: Ghirardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011869:Radioligand Assay / Q000379:methods; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*; D014316:Tritium / Q000493:pharmacokinetics; D014970:Xanthines / Q000493:pharmacokinetics
chemical_list: C506291:2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine; D058917:Adenosine A2 Receptor Antagonists; D014230:Triazoles; D014970:Xanthines; D014316:Tritium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000225:Adenine