A COMMON ACTION OF CLOZAPINE, HALOPERIDOL, AND REMOXIPRIDE ON D-1-DOPAMINERGIC AND D-2-DOPAMINERGIC RECEPTORS IN THE PRIMATE CEREBRAL-CORTEX
A COMMON ACTION OF CLOZAPINE, HALOPERIDOL, AND REMOXIPRIDE ON D-1-DOPAMINERGIC AND D-2-DOPAMINERGIC RECEPTORS IN THE PRIMATE CEREBRAL-CORTEX
复制标题
DOI：
10.1073/pnas.91.10.4353
复制
发表时间：
1994-05-10
影响因子：
11.1
通讯作者：
GOLDMANRAKIC, PS
中科院分区：
文献类型：
--
作者：
LIDOW, MS;GOLDMANRAKIC, PS
用于治疗精神分裂症的主要精神抑制剂（包括氟哌啶醇和瑞莫西必利）的效力与其结合皮质下结构中D-2-多巴胺能受体的能力相关。另一方面，抗精神病药氯氮平对这些位点的亲和力较低，其有益作用的药理学基础尚不清楚。我们已经发现，慢性治疗与氯氮平，氟哌啶醇，和remoxipride上调D-2受体在特定的皮质区域的恒河猴额叶，顶叶，颞叶和枕叶。特别令人感兴趣的是，所有三种精神抑制剂都下调了前额叶和颞叶联合区的D-1受体，这两个区域最常与精神分裂症相关。后一项发现提出了一种可能性，即前额叶和颞叶皮层中D-1受体的下调可能是对神经安定药物的治疗反应的重要组成部分。此外，在大脑皮层中具有不同药理学特征的三种精神抑制剂的共同作用与这种结构是精神分裂症治疗中的主要治疗靶点的想法一致。
The potencies of the major neuroleptics used in the treatment of schizophrenia, including haloperidol and remoxipride, correlate with their ability to bind D-2-dopaminergic receptors in subcortical structures. On the other hand, the neuroleptic clozapine has a low affinity for these sites, and the pharmacological basis of its beneficial action is less clear. We have found that chronic treatment with clozapine, haloperidol, and remoxipride up-regulates D-2 receptors in specific cortical areas of the rhesus monkey frontal, parietal, temporal, and occipital lobes. Of particular interest, all three neuroleptics down-regulated D-1 receptors in prefrontal and temporal association regions-the two areas most often associated with schizophrenia. This latter finding raises the possibility that down-regulation of D-1 receptors in prefrontal and temporal cortex may be an important component of the therapeutic response to neuroleptic drugs. Further, the common effects of three neuroleptics with different pharmacological profiles in the cerebral cortex is consistent with the idea that this structure is a major therapeutic target in the treatment of schizophrenia.