In vivo quantification of striatal dopamine D2 receptor occupancy by JNJ-37822681 using [11C]raclopride and positron emission tomography

Author:

te Beek Erik T1,de Boer Peter2,Moerland Matthijs1,Schmidt Mark E2,Hoetjes Nikie J3,Windhorst Albert D3,van Berckel Bart NM3,Cohen Adam F1,van Gerven Joop MA1,Lammertsma Adriaan A3

Affiliation:

1. Centre for Human Drug Research, Leiden, the Netherlands

2. Janssen Research and Development, a division of Janssen Pharmaceutica NV, Beerse, Belgium

3. Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands

Abstract

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.

Publisher

SAGE Publications

Subject

Pharmacology (medical),Psychiatry and Mental health,Pharmacology

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