Altar C A, Wasley A M, Neale R F, Stone G A
Brain Res Bull. 1986 Apr;16(4):517-25. doi: 10.1016/0361-9230(86)90181-4.
In thin sections of rat brain, [3H]spiperone binds to D2 sites in the basal ganglia (caudate-putamen, nucleus accumbens, olfactory tubercle) and S2 sites in the claustrum and motor cortex. The in vitro displacement of [3H]spiperone from these regions was quantified autoradiographically with the "atypical" neuroleptics clozapine and thioridazine, which ameliorate psychosis, a "typical" neuroleptic, haloperidol, which also induces extrapyramidal side effects, or with metoclopramide, which induces extrapyramidal side effects but is an ineffective antipsychotic. Whereas metoclopramide was equipotent at D2 sites, haloperidol was less potent and clozapine and thioridazine more potent by 2- to 3-fold at competing for D2 sites in the nucleus accumbens or olfactory tubercle than in the caudate-putamen. As measured autoradiographically or with tissue homogenates, clozapine, thioridazine, and five other atypical neuroleptics were 4- to 800-times more potent at competing for S2 sites in the frontal cortex than for D2 sites in the basal ganglia. A preference of atypical antipsychotics for D2 receptors in the nucleus accumbens and olfactory tubercle and for the S2 receptor may explain the relative lack of extrapyramidal side effects produced by these compounds.
在大鼠脑的薄切片中，[3H]司哌罗宁与基底神经节（尾状核 - 壳核、伏隔核、嗅结节）中的D2位点以及屏状核和运动皮层中的S2位点结合。用可改善精神病症状的“非典型”抗精神病药物氯氮平和硫利达嗪、也会诱发锥体外系副作用的“典型”抗精神病药物氟哌啶醇或会诱发锥体外系副作用但抗精神病无效的甲氧氯普胺，通过放射自显影法定量测定这些区域中[3H]司哌罗宁的体外置换情况。甲氧氯普胺在D2位点的效力相当，氟哌啶醇效力较弱，氯氮平和硫利达嗪在伏隔核或嗅结节中竞争D2位点时的效力比在尾状核 - 壳核中高2至3倍。通过放射自显影法或用组织匀浆测定，氯氮平、硫利达嗪和其他五种非典型抗精神病药物在额叶皮层中竞争S2位点时的效力比在基底神经节中竞争D2位点时高4至800倍。非典型抗精神病药物对伏隔核和嗅结节中的D2受体以及S2受体的偏好，可能解释了这些化合物相对缺乏锥体外系副作用的原因。
