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: Maria Antonietta Stasi, Franco Borsini, Katia Varani, Fabrizio Vincenzi, Maria Assunta Di Cesare, Patrizia Minetti, Orlando Ghirardi, Paolo Carminati
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 9 Issue 5 Pg. 575-84 (Oct 2006) ISSN: 1461-1457 [Print] England
• PMID: 16867213 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine
• Adenosine A2 Receptor Antagonists
• Triazoles
• Xanthines
• Tritium
• 1,3-dipropyl-8-cyclopentylxanthine
• Cyclic AMP
• Adenine

Topics

• Adenine (analogs & derivatives, chemistry, pharmacology)
• Adenosine A2 Receptor Antagonists
• Animals
• Behavior, Animal (drug effects)
• CHO Cells (drug effects, metabolism)
• Catalepsy (chemically induced, physiopathology)
• Cricetinae
• Cricetulus
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Drug Interactions
• Humans
• Inhibitory Concentration 50
• Male
• Mice
• Motor Activity (drug effects)
• Radioligand Assay (methods)
• Time Factors
• Transfection (methods)
• Triazoles (chemistry, pharmacology)
• Tritium (pharmacokinetics)
• Xanthines (pharmacokinetics)