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

作者：Kenneth A. Jacobson, Olga Nikodijević, William L. Padgett, Carola Gallo‐Rodriguez, Michel C. Maillard, John W. Daly · 发表于：FEBS Letters · 年份：1993 · DOI：10.1016/0014-5793(93)81466-d · 被引用次数：174 · 研究领域：Adenosine and Purinergic Signaling、Synthesis and Biological Evaluation、Calcium signaling and nucleotide metabolism

An 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 phenochromocytoma cells (Kb 60 nM) vs. A1 receptors in rat adipocytes (Kb 1.3 microM). Administered i.p. in NIH mice at a dose of 1 mg/kg, CSC shifted the curve for locomotor depression elicited by the A2a-selective agonist APEC to the right (ED50 value for APEC shifted from 20 micrograms/kg i.p. to 190 micrograms/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.