Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects.
Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects.
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DOI：
10.1001/archpsyc.1992.01820070032005
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发表时间：
1992-07
影响因子：
--
通讯作者：
L. Farde;A. Nordström;F. Wiesel;S. Pauli;C. Halldin;G. Sedvall
中科院分区：
文献类型：
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作者：
L. Farde;A. Nordström;F. Wiesel;S. Pauli;C. Halldin;G. Sedvall
应用正电子发射断层扫描和选择性放射配体检测抗精神病药对基底节区D1和D2多巴胺受体占用的影响。在22例使用常规剂量的经典抗精神病药物治疗的患者中，D2占用率为70%至89%。急性锥体外系综合征患者D2占用率高于无副作用患者。这一发现表明，抗精神病药诱导的锥体外系综合征与基底节区D2占据中枢的程度有关。在使用氯氮平（原型非典型抗精神病药物）治疗的5例患者中，D2的占用率较低，为38%至63%。这一发现表明氯氮平在患者D2中央占位方面也是“非典型”的。在氯氮平治疗期间，锥体外系综合征的发生率较低，这可能反映了氯氮平临床剂量所致D2占用率较低。经典的抗精神病药，如氟哌啶醇或舒必利，没有引起明显的D1占位，但硫代蒽氟替索引起36%至44%的D1占位。在4例接受氯氮平治疗的患者中，D1占用率为38%至52%。氯氮平和氟哌噻索诱导的D1占用可能有助于这些药物的抗精神病作用。
Positron emission tomography and selective radioligands were used to determine D1 and D2 dopamine receptor occupancy induced by neuroleptics in the basal ganglia of drug-treated schizophrenic patients. In 22 patients treated with conventional dosages of classical neuroleptics, the D2 occupancy was 70% to 89%. Patients with acute extrapyramidal syndromes had a higher D2 occupancy than those without side effects. This finding indicates that neuroleptic-induced extrapyramidal syndromes are related to the degree of central D2 occupancy induced in the basal ganglia. In five patients treated with clozapine, the prototype atypical antipsychotic drug, a lower D2 occupancy of 38% to 63% was found. This finding demonstrates that clozapine is also "atypical" with respect to the central D2 occupancy in patients. During treatment with clozapine, there is a low frequency of extrapyramidal syndromes, which accordingly may reflect the comparatively low D2 occupancy induced by clinical doses of clozapine. Classical neuroleptics, like haloperidol or sulpiride, did not cause any evident D1 occupancy, but the thioxanthene flupentixol induced a 36% to 44% occupancy. In four patients treated with clozapine, the D1 occupancy was 38% to 52%. The D1 occupancy induced by clozapine and flupentixol may contribute to the antipsychotic effect of these drugs.