Characterization of the locomotor depression produced by an A 2 ‐selective adenosine agonist

Adenosine analogs, such as N 6 ‐cyclohexyladenosine (CHA) that are selective for A 1 ‐adenosine receptors, and analogs, such as 5'‐ N ‐ethylcarboxamidoadenosine (NECA) that are active at both a 1 and A 2 receptors, cause a profound depression of locomotor activity in mice via a central mechanism. The depression is effectively reversed by non‐selective adenosine antagonists such as theophylline. We report that 2‐[(2‐aminoethyl‐amino) carbonylethylphenylethylamino]‐5'‐ N ‐ethylcarboxamidoadenosine (APEC), an amine derivative of the A 2 selective agonist, CGS21680, is a potent locomotor depressant in mice. The in vivo pharmacology is consistent with A 2 ‐selectivity at a central site of action. Two parameters indicative of locomotor activity, horizontal activity and total distance travelled, were measured using a computerized activity monitor. From dose‐respon‐ se curves it was found that APEC (ED 50 16 ) is more potent than CHA (ED 50 60 ) and less potent than NECA (ED 50 2 ) . The locomotor depression by APEC was reversible by theophylline, but not by the A 1 ‐selective antagonists 8‐cyclopentyltheophylline (CPT) and 8‐cyclo‐pentyl‐1,3‐dipropyl‐2‐thioxanthine, nor by the peripheral antagonists 8‐ p ‐sulfophenyltheophylline (8‐PST) and 1,3‐dipropyl‐8‐ P ‐sulfophenylxanthine. The locomotor activity depression elicited by NECA and CHA was reversed by A 1 ‐selective antagonists. These results suggest that the effects of APEC are due to stimulation of A 2 adenosine receptors in the brain.