Occupancy of Striatal and Extrastriatal Dopamine D2/D3 Receptors by Olanzapine and Haloperidol

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Abstract
There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D2/D3 receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D2/D3 receptors. We performed [18F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [18F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT2A receptor occupancy. Occupancy of dopamine D2/D3 receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5–78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D2/D3 receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D2/D3 receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D2/D3 receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p2A receptors was 85–93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D2/D3 receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D2/D3 receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.