Comparison of Dopamine D(3) and D(2) Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [(11)C]-(+)-PHNO

BACKGROUND: Blockade of D(3) receptor, a member of the dopamine D(2)-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D(3) as well as D(2) receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8–24 mg) for the treatment of schizophrenia, occupies D(3) as well as D(2) receptors in healthy subjects. METHODS: Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [(11)C]-(+)-PHNO. RESULTS: Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%–81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%–84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%–88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%–87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%–88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D(2)-rich (caudate and putamen) and D(3)-rich (globus pallidus and substantia nigra) regions showed that EC(50) for D(2)-rich region was 0.39 ng/mL (r=0.43) and EC(50) for D(3)-rich region was 0.40 ng/mL (r=0.79). CONCLUSIONS: A single dose of 12 mg blonanserin occupied D(3) receptor to the same degree as D(2) receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D(3) receptor antagonism.