JNJ-10397049 is a potent, selective, and bioavailable antagonist of the orexin-2 receptor (OX2R) (KB = 4.5 nM for OX2R versus 1.1 μM for OX1R). It has no significant affinity for over 50 other neurotransmitters or neuropeptide receptors. Applied subcutaneously to rats, JNJ-10397049 decreases the latency to persistent sleep and increases persistent sleep time. This compound produces a widespread attenuation of D-amphetamine-induced relative cerebrovascular signal, with prominent cortical involvement, in rat brains assessed by functional magnetic resonance imaging.
