Kapur S, Zipursky R B, Remington G
The Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, ON, Canada.
Am J Psychiatry. 1999 Feb;156(2):286-93. doi: 10.1176/ajp.156.2.286.
Dopamine D2 receptor occupancy measurements provide a valid predictor of antipsychotic response, extrapyramidal side effects, and elevation of prolactin levels. The new antipsychotics clozapine, risperidone, and olanzapine obtain antipsychotic response with few extrapyramidal side effects and little prolactin elevation. The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens.
Forty-four patients with schizophrenia (16 taking risperidone, 2-12 mg/day; 17 taking olanzapine, 5-60 mg/day; and 11 taking clozapine, 75-900 mg/day) had their D2 and 5-HT2 occupancies determined with the use of [11C]raclopride and [18F]setoperone, respectively, and positron emission tomography imaging.
Clozapine showed a much lower D2 occupancy (16%-68%) than risperidone (63%-89%) and olanzapine (43%-89%). Risperidone and olanzapine gave equal D2 occupancies at doses of 5 and 20 mg/day, respectively. All three drugs showed greater 5-HT2 than D2 occupancy at all doses, although the difference was greatest for clozapine.
Clozapine, at doses known to be effective in routine clinical settings, showed a D2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antipsychotics. The results also suggest that some previous clinical comparisons of antipsychotics may have been confounded by different levels of D2 occupancy. Clinical comparisons of these drugs, matching for D2 occupancy, may provide a better measure of their true "atypicality" and will help in understanding the contribution of non-D2 receptors to antipsychotic effects.
多巴胺D2受体占有率测量可有效预测抗精神病药物的疗效、锥体外系副作用及催乳素水平升高情况。新型抗精神病药物氯氮平、利培酮和奥氮平具有抗精神病疗效，且锥体外系副作用较少，催乳素升高不明显。本研究旨在比较接受多剂量稳态治疗方案的患者中这些药物对D2和5-羟色胺5-HT2受体的占有率。
44例精神分裂症患者（16例服用利培酮，2 - 12毫克/天；17例服用奥氮平，5 - 60毫克/天；11例服用氯氮平，75 - 900毫克/天）分别使用[11C]雷氯必利和[18F]司托哌隆及正电子发射断层扫描成像测定其D2和5-HT2受体占有率。
氯氮平的D2受体占有率（16% - 68%）远低于利培酮（63% - 89%）和奥氮平（43% - 89%）。利培酮和奥氮平在每日剂量分别为5毫克和20毫克时D2受体占有率相同。所有三种药物在所有剂量下5-HT2受体占有率均高于D2受体占有率，尽管氯氮平的差异最大。
在已知对常规临床有效剂量下，氯氮平的D2受体占有率明显低于典型抗精神病药物，而利培酮和奥氮平在其常用临床剂量下的D2受体占有率与低剂量典型抗精神病药物相同。结果还表明，之前一些抗精神病药物的临床比较可能因D2受体占有率不同而受到混淆。这些药物在D2受体占有率匹配情况下的临床比较可能会更好地衡量其真正的“非典型性”，并有助于理解非D2受体对抗精神病作用的贡献。
