Evaluation of dopamine D₃ receptor occupancy by blonanserin using [¹¹C]-(+)-PHNO in schizophrenia patients

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.

We examined D₂ and D₃ receptor occupancies in patients with schizophrenia who had been treated with blonanserin.

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 (BP_ND) 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 BP_ND of olanzapine condition as baseline.

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 BP_ND of olanzapine condition as baseline.

Our study confirmed that blonanserin occupied both D₂ and D₃ receptors in patients with schizophrenia.