Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-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 [C-11]-(+)-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 EC50 for D-2-rich region was 0.39 ng/mL (r =0.43) and EC, for D-3-rich region was 0.40 ng/mL (r=0.79). Conclusions: A single dose of 12 mg blonanserin occupied D-1 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.