Kessler Robert M, Ansari Mohammad Sib, Riccardi Patrizia, Li Rui, Jayathilake Karuna, Dawant Benoit, Meltzer Herbert Y
Department of Radiology, Vanderbilt University School of Medicine, University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA.
Neuropsychopharmacology. 2005 Dec;30(12):2283-9. doi: 10.1038/sj.npp.1300836.
There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D(2)/D(3) receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors. We performed [(18)F] 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. [(18)F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT(2A) receptor occupancy. Occupancy of dopamine D(2)/D(3) 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 D(2)/D(3) receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D(2)/D(3) 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 D(2)/D(3) receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT(2A) 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 D(2)/D(3) receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D(2)/D(3) receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.
关于奥氮平与典型抗精神病药物相比是否能降低纹状体多巴胺D(2)/D(3)受体占有率以及是否优先占据纹状体以外的多巴胺D(2)/D(3)受体，一直存在相互矛盾的报道。我们对6名接受奥氮平治疗的精神分裂症患者和6名接受氟哌啶醇治疗的精神分裂症患者进行了[(18)F]法利哌德PET研究，以检测这些抗精神病药物对纹状体和纹状体以外多巴胺受体的占有率。对7名接受奥氮平治疗的患者进行了[(18)F]司托哌隆PET研究，以确定5-HT(2A)受体占有率。奥氮平对多巴胺D(2)/D(3)受体的占有率在壳核、腹侧纹状体、内侧丘脑、杏仁核或颞叶皮质中与氟哌啶醇所见无显著差异，即占有率为67.5 - 78.2%；奥氮平在腹侧纹状体、内侧丘脑、杏仁核或颞叶皮质中未优先占据多巴胺D(2)/D(3)受体。然而，与接受氟哌啶醇治疗的患者相比，接受奥氮平治疗的患者黑质/腹侧被盖区多巴胺D(2)/D(3)受体占有率显著降低，即分别为40.2%和59.3%（经多重比较校正后p = 0.0014）；在接受奥氮平治疗的患者中，黑质/腹侧被盖区是唯一多巴胺D(2)/D(3)受体占有率显著低于壳核的区域，即分别为40.2%和69.2%（经多重比较校正后p < 0.001）。在接受奥氮平治疗的患者中，5-HT(2A)受体占有率为85 - 93%。本研究结果表明，奥氮平不会优先占据纹状体以外的多巴胺D(2)/D(3)受体，但确实会使黑质/腹侧被盖区受体免受影响。黑质/腹侧被盖区多巴胺D(2)/D(3)受体占有率降低可能是奥氮平治疗患者锥体外系副作用发生率较低的原因。
