In vivo quantification of striatal dopamine D 2 receptor occupancy by JNJ-37822681 using [ 11 C]raclopride and positron emission tomography

JNJ-37822681 is a novel, fast-dissociating dopamine D₂ receptor antagonist, currently in development as an antipsychotic drug candidate. A previous first-in-human study demonstrated mild central nervous system effects of JNJ-37822681 in healthy male volunteers. Significant but transient serum prolactin elevations were demonstrated, whereas other neurophysiological effects were relatively small. To investigate striatal dopamine D₂ receptor occupancy by variable single doses of JNJ-37822681, an open-label [¹¹C]raclopride positron emission tomography study was performed in 12 healthy male volunteers, using the simplified reference tissue model with cerebellum as reference tissue. Oral administration of JNJ-37822681 resulted in dose-dependent dopamine D₂ receptor occupancy. Receptor occupancy increased from 9–19% at 2 mg doses to 60–74% at 20 mg doses of JNJ-37822681. Therefore, single oral doses of JNJ-37822681 can produce occupancy levels that are generally associated with clinical efficacy for registered antipsychotic drugs.