Blonanserin is a novel
antipsychotic with high affinities for
dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of
schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that
blonanserin has equal efficacy to
risperidone, and with a better profile especially with respect to
prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with
schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal
dopamine D(2) receptor occupancy by
blonanserin in 15 patients with
schizophrenia treated with fixed doses of
blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]
raclopride for the striatum and 1 with [(11)C]
FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal
dopamine D(2) receptor occupancy by
blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of
blonanserin occupying
dopamine D(2) receptors in patients with
schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of
blonanserin required for 70% to 80%
dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of
hyperprolactinemia.