Abstract

CGS 15943A, a triazoloquinazoline, is a potent and selective adenosine receptor antagonist as assessed by its effects on radioligand binding and adenosine-stimulated adenylate cyclase activity in guinea pig synaptoneurosomes. At the adenosine A-1 receptor labeled with [3H]cyclohexyladenosine, CGS 15943A had an IC50 value of 20 nM. At the striatal A-2 receptor labeled with [3H]5'-N-ethylcarboxamidoadenosine in the presence of a low concentration of cyclopentyladenosine to block A-1 receptors labeled by this nonselective adenosine agonist, CGS 15943A had an IC50 value of 3 nM, indicating that the compound had some degree of selectivity for the A-2 receptor. Analysis of the effect of the compound on the saturation isotherms for each of the receptors indicated that it was a competitive antagonist at the brain A-1 receptor but that it was noncompetitive at the striatal A-2 receptor. CGS 15943A was a potent adenosine antagonist in the adenosine-stimulated adenylate cyclase system in guinea pig synaptoneurosomes, where the compound was found to have an IC50 value of 30 to 70 nM against the increase in cyclic AMP evoked by 5 microM adenosine. CGS 15943A had no effect on the binding of [3H]nitrobenzylthioinosine, a ligand thought to bind to adenosine uptake sites, and, at a concentration of 10 microM, had no effect on beef heart type III phosphodiesterase activity.(ABSTRACT TRUNCATED AT 250 WORDS)