Nyberg S, Nilsson U, Okubo Y, Halldin C, Farde L
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Int Clin Psychopharmacol. 1998 Mar;13 Suppl 3:S15-20. doi: 10.1097/00004850-199803003-00003.
Positron emission tomography (PET) can be used to explore relationships between central neuroreceptor occupancy, psychotropic drug blood levels and clinical effects. Treatment with conventional neuroleptics induces high (70-90%) dopamine (D2)-receptor occupancy. The risk of extrapyramidal side effects increases at D2-receptor occupancies above 80%. Standard doses of clozapine induced a low (20-67%) D2-receptor occupancy, but very high (85-90%) 5-hydroxytryptamine (5-HT2A)-receptor occupancy. The novel antipsychotics risperidone and olanzapine induced high occupancy of both D2 and 5-HT2A receptors at suggested standard doses. The occurrence of extrapyramidal side effects in some patients in the higher dose ranges does not support the view that 5-HT2A-receptor occupancy completely prevents the development of extrapyramidal side effects. These results emphasize the need for further exploration of the low dose ranges of risperidone and olanzapine. A preliminary analysis of an ongoing PET study showed that a schizophrenic patient treated with sertindole at 20 mg/day had a D2-receptor occupancy of below 70%. Further studies are needed to show whether sertindole is the first new antipsychotic that induces low occupancy in the clinical dose range, suggesting a mechanism of action distinct from that of classical neuroleptics and analogous to that of clozapine.
正电子发射断层扫描（PET）可用于探究中枢神经受体占有率、精神药物血药浓度与临床疗效之间的关系。使用传统抗精神病药物治疗会导致较高（70-90%）的多巴胺（D2）受体占有率。当D2受体占有率超过80%时，锥体外系副作用的风险会增加。氯氮平的标准剂量会导致较低（20-67%）的D2受体占有率，但5-羟色胺（5-HT2A）受体占有率非常高（85-90%）。新型抗精神病药物利培酮和奥氮平在建议的标准剂量下会导致D2和5-HT2A受体的高占有率。在较高剂量范围内，一些患者出现锥体外系副作用，这并不支持5-HT2A受体占有率能完全预防锥体外系副作用发生的观点。这些结果强调了进一步探索利培酮和奥氮平低剂量范围的必要性。一项正在进行的PET研究的初步分析表明，一名每天服用20mg舍吲哚的精神分裂症患者的D2受体占有率低于70%。需要进一步研究以确定舍吲哚是否是首个在临床剂量范围内诱导低占有率的新型抗精神病药物，这表明其作用机制不同于经典抗精神病药物，与氯氮平类似。
