Comparison of Dopamine [D.sub.3] and [D.sub.2] Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [[.sup11]C]--PHNO

• Published in: The international journal of neuropsychopharmacology Vol. 21; no. 6; p. 522
• Main Authors: Tateno, Amane, Sakayori, Takeshi, Kim, Woo-chan, Honjo, Kazuyoshi, Nakayama, Haruo, Arakawa, Ryosuke, Okubo, Yoshiro
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01-06-2018
• Subjects: Aripiprazole; Cardiac glycosides; Cardiotonic agents; Ethylenediaminetetraacetic acid; PET imaging; Phenols; Schizophrenia
• ISSN: 1461-1457
• DOI: 10.1093/ijnp/pyy004

Background: Blockade of [D.sub.3] receptor, a member of the dopamine [D.sub.2]-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for [D.sub.3] as well as [D.sub.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.sub.3] as well as [D.sub.2] receptors in healthy subjects. Methods: Six healthy males (mean 35.7 [+ or -] 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 [[.sup.11]C]-(+)-PHNO. Results: Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean [+ or -] SD, 74.3 [+ or -] 5.6%), putamen (range 60.4%-84.3%; mean [+ or -] SD, 73.3% [+ or -] 8.2%), ventral striatum (range 40.1%-88.2%; mean [+ or -] SD, 60.8% [+ or -] 17.1%), globus pallidus (range 65.8%-87.6%; mean [+ or -] SD, 75.7% [+ or -] 8.6%), and substantia nigra (range 56.0%-88.7%; mean [+ or -] SD, 72.4% [+ or -] 11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in [D.sub.2]-rich (caudate and putamen) and [D.sub.3]-rich (globus pallidus and substantia nigra) regions showed that [EC.sub.50] for [D.sub.2]-rich region was 0.39 ng/mL (r=0.43) and [EC.sub.50] for [D.sub.3]-rich region was 0.40 ng/mL (r=0.79). Conclusions: A single dose of 12 mg blonanserin occupied [D.sub.3] receptor to the same degree as [D.sub.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.sub.3] receptor antagonism. Keywords: [D.sub.2] receptor, [D.sub.3] receptor, blonanserin, positron emission tomography