Evaluation of dopamine D 3 receptor occupancy by blonanserin using [ 11 C]-(+)-PHNO in schizophrenia patients
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ORIGINAL INVESTIGATION
Evaluation of dopamine D3 receptor occupancy by blonanserin using [11C]-(+)-PHNO in schizophrenia patients Takeshi Sakayori 1 & Amane Tateno 1 & Ryosuke Arakawa 1 & Woo-chan Kim 1 & Yoshiro Okubo 1 Received: 23 April 2020 / Accepted: 30 October 2020 # The Author(s) 2020
Abstract Rationale Unlike other antipsychotics, our previous positron emission tomography (PET) study demonstrated that a single dose of blonanserin occupied dopamine D3 as well as dopamine D2 receptors in healthy subjects. However, there has been no study concerning the continued use of blonanserin. Objectives We examined D2 and D3 receptor occupancies in patients with schizophrenia who had been treated with blonanserin. Methods Thirteen patients with schizophrenia participated. PET examinations were performed on patients treated with clinical dosage of blonanserin or olanzapine alone. A crossover design was used in which seven patients switched drugs after the first scan, and PET examinations were conducted again. D2 and D3 receptor occupancies were evaluated by [11C]-(+)-PHNO. We used nondisplaceable binding potential (BPND) of 6 healthy subjects which we previously reported as baseline. To consider the effect of upregulation of D3 receptor by continued use of antipsychotics, D3 receptor occupancy by blonanserin in seven subjects who completed 2 PET scans were re-analyzed by using BPND of olanzapine condition as baseline. Results Average occupancy by olanzapine (10.8 ± 6.0 mg/day) was as follows: caudate 32.8 ± 18.3%, putamen 26.3 ± 18.2%, globus pallidus − 33.7 ± 34.9%, substantia nigra − 112.8 ± 90.7%. Average occupancy by blonanserin (12.8 ± 5.6 mg/day) was as follows: caudate 61.0 ± 8.3%, putamen 55.5 ± 9.5%, globus pallidus 48.9 ± 12.4%, substantia nigra 34.0 ± 20.6%. EC50 was 0.30 ng/mL for D2 receptor for caudate and putamen (df = 19, p < 0.0001) and 0.70 ng/mL for D3 receptor for globus pallidus and substantia nigra (df = 19, p < 0.0001). EC50 for D3 receptor of blonanserin changed to 0.22 ng/mL (df = 13, p = 0.0041) when we used BPND of olanzapine condition as baseline. Conclusions Our study confirmed that blonanserin occupied both D2 and D3 receptors in patients with schizophrenia. Keywords D3 receptor . Schizophrenia . Blonanserin . Positron emission tomography
Introduction The dopamine D2 receptor family contains 3 subtypes (D2, D3, and D4), and they are known as the D2-like receptor family. In terms of the treatment of schizophrenia, D2 receptor has been thought to be strongly associated with the pathology of schizophrenia and be a major target for its treatment. Dopamine D3 receptor has similarities to the other members of the D2-like receptor family, but D3 receptor has very high This article belongs to a Special Issue on Imaging for CNS drug development and biomarkers. * Yoshiro Okubo [email protected] 1
Department of Neuropsychiatry, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113–8602, Japan
affinity for dopamine and modulates dopamine release as an autoreceptor (Gross and Drescher 2012). D
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