8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo

AbstractAn adenosine antagonist, 8-(3-chlorostyryl)caffeine (CSC), was shown previously to be 520-fold selective for A2a-adenosine receptors in radioligand binding assays in the rat brain. In reversing agonist effects on adenylate cyclase, CSC was 22-fold selective for A2a receptors in rat pheochromocytoma cells (Kb 60 nM) vs. A1 receptors in rat adipocytes (Kb 1.3 μM). Administered i.p. in NIH mice at a dose of 1 mgkg, CSC shifted the curve for locomotor depression elicited by the A2a-selective agonist APEC to the right (ED50 value for APEC shifted from 20 μgkg i.p. to 190 μgkg). CSC had no effect on locomotor depression elicited by an ED50 dose of the A1-selective agonist CHA. CSC alone at a dose of 5 mgkg stimulated locomotor activity by 22% over control values. Coadministration of CSC and the A1-selective antagonist CPX, both at non-stimulatory doses, increased activity by 37% (P < 0.001) over CSC alone, suggesting a behavioral synergism of A1- and A2-antagonist effects in the CNS