Gotoh Y, Shibanoki S, Ishikawa K
Jpn J Pharmacol. 1986 Feb;40(2):231-7. doi: 10.1254/jjp.40.231.
The direct correlation analyses between the distribution of chlorpromazine (pharmacokinetics) and the biochemical effects of the drug on monoamine metabolisms (pharmacodynamics) are reported. Both samples for quantitative determination of CPZ and of monoamine transmitters and metabolites were obtained by organic extraction procedures from the same sample. The determinations were carried out by high performance liquid chromatography with electrochemical detection. CPZ affected the concentrations of metabolites of noradrenaline, dopamine and 5-hydroxytryptamine, but not those of the monoamine transmitters themselves. However, simultaneous assay demonstrated differences in effects of the drug on the transmitter systems. The concentrations of HVA and DOPAC were increased over a wide range of intracerebral concentrations of the drug, but those of MOPEG, in the range of higher concentrations. On the other hand, CPZ did not reveal any correlations between the intracerebral concentrations of the drug and 5-HIAA. These results suggest that CPZ affected primarily the dopaminergic system rather than the serotonergic one in the early stage of its biochemical actions. The proposed procedure is demonstrated to be simple and useful as a new approach in biochemical pharmacology. The same procedure can be applicable for other centrally acting drugs.
本文报道了氯丙嗪分布（药代动力学）与该药物对单胺代谢的生化效应（药效动力学）之间的直接相关性分析。用于定量测定氯丙嗪以及单胺递质和代谢物的样本均通过有机萃取程序从同一样本中获取。测定采用高效液相色谱 - 电化学检测法进行。氯丙嗪影响去甲肾上腺素、多巴胺和5 - 羟色胺代谢物的浓度，但不影响单胺递质本身的浓度。然而，同时检测表明该药物对递质系统的影响存在差异。在药物脑内浓度的广泛范围内，高香草酸（HVA）和3,4 - 二羟基苯乙酸（DOPAC）的浓度升高，但在较高浓度范围内，3 - 甲氧基 - 4 - 羟基苯乙二醇（MOPEG）的浓度升高。另一方面，氯丙嗪并未显示出药物脑内浓度与5 - 羟吲哚乙酸（5 - HIAA）之间存在任何相关性。这些结果表明，在其生化作用的早期阶段，氯丙嗪主要影响多巴胺能系统而非5 - 羟色胺能系统。所提出的方法被证明是一种简单且有用的生物化学生理学新方法。相同的方法可应用于其他中枢作用药物。
