Premium
8‐(3‐Chlorostyryl)caffeine (CSC) is a selective A 2 ‐adenosine antagonist in vitro and in vivo
Author(s) -
Jacobson Kenneth A.,
Nikodijević Olga,
Padgett William L.,
Gallo-Rodriguez Carola,
Maillard Michel,
Daly John W.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81466-d
Subject(s) - agonist , antagonist , caffeine , adenosine , chemistry , pharmacology , adenosine receptor , endocrinology , receptor , medicine , in vivo , adenosine receptor antagonist , biology , biochemistry , microbiology and biotechnology
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. A 1 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 (ED 50 value for APEC shifted from 20 μg/kg i.p. to 190 μg/kg). CSC had no effect on locomotor depression elicited by an ED 50 dose of the A 1 ‐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 A 1 ‐selective antagonist CPX, both at non‐stimulatory doses, increased activity by 37% ( P < 0.001) over CSC alone, suggesting a behavioral synergism of A 1 ‐ and A 2 ‐antagonist effects in the CNS.