Evaluation of dopamine D(3) receptor occupancy by blonanserin using [(11)C]-(+)-PHNO in schizophrenia patients

RATIONALE: Unlike other antipsychotics, our previous positron emission tomography (PET) study demonstrated that a single dose of blonanserin occupied dopamine D(3) as well as dopamine D(2) receptors in healthy subjects. However, there has been no study concerning the continued use of blonanserin. OBJECTIVES: We examined D(2) and D(3) 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. D(2) and D(3) receptor occupancies were evaluated by [(11)C]-(+)-PHNO. We used nondisplaceable binding potential (BP(ND)) of 6 healthy subjects which we previously reported as baseline. To consider the effect of upregulation of D(3) receptor by continued use of antipsychotics, D(3) receptor occupancy by blonanserin in seven subjects who completed 2 PET scans were re-analyzed by using BP(ND) 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%. EC(50) was 0.30 ng/mL for D(2) receptor for caudate and putamen (df = 19, p < 0.0001) and 0.70 ng/mL for D(3) receptor for globus pallidus and substantia nigra (df = 19, p < 0.0001). EC(50) for D(3) receptor of blonanserin changed to 0.22 ng/mL (df = 13, p = 0.0041) when we used BP(ND) of olanzapine condition as baseline. CONCLUSIONS: Our study confirmed that blonanserin occupied both D(2) and D(3) receptors in patients with schizophrenia.