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

摘要

>An adenosine antagonist, 8-(3-chlorostyryl)caffeine (CSC), was shown previously to be 520-fold selective for A_2a-adenosine receptors in radioligand binding assays in the rat brain. In reversing agonist effects on adenylate cyclase, CSC was 22-fold selective for A_2a receptors in rat pheochromocytoma cells (K _b 60 nM) vs. A₁ receptors in rat adipocytes (K _b 1.3 μM). Administered i.p. in NIH mice at a dose of 1 mg/kg, CSC shifted the curve for locomotor depression elicited by the A_2a-selective agonist APEC to the right (ED₅₀ value for APEC shifted from 20 μg/kg i.p. to 190 μg/kg). 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 mg/kg 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.