JNJ-40255293 (JNJ 40255293) is a potent, dual adenosine A2A/A1 receptor antagonist with Ki of 6.8/42 nM, respectively.
JNJ-40255293 shows weaker affinity for A2B/A3 receptors with binding Ki of 230/9200 nM, respectively.
JNJ-40255293 shows similar A2A:A1 selectivity (7-fold) in vivo (ED50s of 0.21 and 2.1 mg/kg p.o. for occupancy of rat brain A2A and A1 receptors, respectively).
JNJ-40255293 dose-dependently enhanced a consolidated waking associated with a subsequent delayed compensatory sleep (EC50= 0.63 mg/kg p.o.) in sleep–wake encephalographic (EEG) studies.
JNJ-40255293 did not affect dopamine and noradrenaline release in the prefrontal cortex and the striatum.
JNJ-40255293 potentiated the agitation induced by the dopamine agonist apomorphine.
JNJ-40255293 also reversed hypolocomotion produced by the dopamine-depleting agent reserpine and potentiated the effects of l-dihydroxyphenylalanine (L-DOPA) in rats.