Characterization of the locomotor depression produced by an A2‐selective adenosine agonist

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Abstract
Adenosine analogs, such as N6‐cyclohexyladenosine (CHA) that are selective for A1‐adenosine receptors, and analogs, such as 5'‐N‐ethylcarboxamidoadenosine (NECA) that are active at both a1 and A2 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 A2 selective agonist, CGS21680, is a potent locomotor depressant in mice. The in vivo pharmacology is consistent with A2‐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 (ED50 16 ) is more potent than CHA (ED50 60 ) and less potent than NECA (ED50 2 ). The locomotor depression by APEC was reversible by theophylline, but not by the A1‐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 A1‐selective antagonists. These results suggest that the effects of APEC are due to stimulation of A2 adenosine receptors in the brain.