Pizzolato G, Soncrant T T, Rapoport S I
J Neurochem. 1984 Sep;43(3):724-32. doi: 10.1111/j.1471-4159.1984.tb12792.x.
The time course and distribution of alterations in cerebral metabolic activity after haloperidol administration were evaluated in relation to the pharmacokinetics of haloperidol and the topography of the dopaminergic system in the brain. Local cerebral glucose utilization was measured, using the 2-deoxyglucose technique, in awake rats after i.p. administration of the dopamine antagonist haloperidol (0.5 or 1 mg/kg). Haloperidol significantly reduced glucose utilization in 60% of 59 brain regions examined, but produced a large increase in the lateral habenula. The regional distribution of changes in glucose utilization was not closely related to the known anatomy of the brain dopaminergic system. The time course of the effect of haloperidol on cerebral metabolism was different for the two doses studied (0.5 and 1 mg/kg), and was not simply related to estimated brain concentrations of haloperidol. However, a linear relation between the metabolic effect and the time-integrated brain concentration was demonstrated. These results show that haloperidol has an effect on CNS metabolic activity that is more widespread than would be predicted from the topography of the dopaminergic system; this may be due to indirect propagation of the primary effects of haloperidol. The metabolic response to haloperidol depends on brain concentration and duration of exposure to the drug.
研究了氟哌啶醇给药后脑代谢活动变化的时间进程和分布，及其与氟哌啶醇的药代动力学和脑中多巴胺能系统拓扑结构的关系。采用2-脱氧葡萄糖技术，在腹腔注射多巴胺拮抗剂氟哌啶醇（0.5或1mg/kg）后的清醒大鼠中测量局部脑葡萄糖利用率。氟哌啶醇使所检测的59个脑区中的60%葡萄糖利用率显著降低，但使外侧缰核的葡萄糖利用率大幅增加。葡萄糖利用率变化的区域分布与已知的脑多巴胺能系统解剖结构关系不紧密。所研究的两种剂量（0.5和1mg/kg）的氟哌啶醇对脑代谢的作用时间进程不同，且与估计的脑内氟哌啶醇浓度无简单关联。然而，证明了代谢效应与时间积分脑浓度之间存在线性关系。这些结果表明，氟哌啶醇对中枢神经系统代谢活动的影响比根据多巴胺能系统拓扑结构所预测的更为广泛；这可能是由于氟哌啶醇主要作用的间接传播。对氟哌啶醇的代谢反应取决于脑浓度和药物暴露持续时间。
