Coppens H J, Slooff C J, Paans A M, Wiegman T, Vaalburg W, Korf J
Department of Clinical Psychiatry, Groningen University, The Netherlands.
Biol Psychiatry. 1991 Apr 1;29(7):629-34. doi: 10.1016/0006-3223(91)90132-6.
We investigated whether the lack of therapeutic response to long-term and adequate neuroleptic treatment was due to a failure to achieve a blockade of cerebral dopamine receptors. Six chronic schizophrenic and medicated patients (DSM-III-R diagnosis, paranoid or disorganized type) were assessed with the Present State Examination and the Brief Psychiatric Rating Scale. According to the Chouinard Rating Scale there were little extrapyramidal symptoms, although no anticholinergic drugs were given. Plasma levels of the neuroleptics were determined and found in the therapeutic range or higher. Dopamine D2-receptor occupancy was determined with positron emission tomography using 11C-methylspiperone as ligand. There was a more than 95% blockade of the D2 receptors in the striatum. These results indicate that the lack of therapeutic response and extra-pyramidal side effects cannot be attributed to an incomplete blockade of cerebral D2 receptors and that the pathogenetic role of these receptors can be questioned in therapy-resistant schizophrenic patients.
我们研究了长期足量使用抗精神病药物治疗无效是否是由于未能实现脑内多巴胺受体的阻断。对6例慢性精神分裂症且正在接受药物治疗的患者（DSM-III-R诊断，偏执型或紊乱型）采用现况检查和简明精神病评定量表进行评估。根据乔伊纳德评定量表，尽管未给予抗胆碱能药物，但锥体外系症状很少。测定了抗精神病药物的血浆水平，发现其处于治疗范围或更高。使用11C-甲基螺哌隆作为配体，通过正电子发射断层扫描测定多巴胺D2受体占有率。纹状体中D2受体的阻断率超过95%。这些结果表明，治疗无效和锥体外系副作用不能归因于脑内D2受体的不完全阻断，并且在治疗抵抗性精神分裂症患者中，这些受体的致病作用可能受到质疑。
