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[甲基苯丙胺和一种利血平样药物对大鼠脑内去甲肾上腺素和多巴胺代谢的影响]

[Effects of methamphetamine and a reserpine-like drug on norepinephrine and dopamine metabolism in the rat brain].

作者信息

Nozu T, Furukawa T

出版信息

Nihon Yakurigaku Zasshi. 1976 May;72(4):445-51. doi: 10.1254/fpj.72.445.

Abstract

Simple and sensitive methods for the separation and determination of catecholamines and their metabolites by thinlayer microcrystalline cellulose chromatography have been developed and applied to the analysis of norepinephrine (NE) and dopamine (DA) metabolism in the brain of Wistar rats given 12C-NE or 14C-DA intraventricularly. 14C-DA in the whole brain declined more rapidly than did 14C-NE. The percentage of unchanged 14C-NE in total radioactivity in the brain of rats administered 14C-NI was high, while on the other hand, the percentage of unchanged 14C-DA in cases of 14C-DA was low. In the metabolism of 14C-DA, the deaminated and O-methylated deaminated metabolites showed transient and delayed temporary rises, respectively. Drugs which affect the metabolism of catecholamines were also examined. Methamphetamine reduced NE, deaminated and O-methylated deaminated metabolites, and markedly elevated normetanephrine in the brain of rats given 14C-NE. Regarding the metabolism of DA, methamphetamine increased 3-methoxytyramine and homovanillic acid and reduced deaminated metabolites, but had no effect on DA and NE. On the other hand, a reserpine-like drug (Ro4-1284) reduced NE and increased deaminated and O-methylated deaminated metabolites in the metabolism of NE, and reduced to a great extent DA and NE and increased homovanillic acid in the metabolism of DA. From these results, it is concluded that the effect of methamphetamine was more evident in NE metabolism than DA, while the effect of Ro4-1284 was more evident in DA metabolism than NE.

摘要

已开发出通过薄层微晶纤维素色谱法分离和测定儿茶酚胺及其代谢物的简单且灵敏的方法,并将其应用于对经脑室内注射12C-去甲肾上腺素(NE)或14C-多巴胺(DA)的Wistar大鼠脑内去甲肾上腺素(NE)和多巴胺(DA)代谢的分析。全脑中的14C-DA比14C-NE下降得更快。在给予14C-NE的大鼠脑中,未变化的14C-NE在总放射性中的百分比很高,而另一方面,在给予14C-DA的情况下,未变化的14C-DA的百分比很低。在14C-DA的代谢中,脱氨基代谢物和O-甲基化脱氨基代谢物分别呈现出短暂和延迟的暂时升高。还研究了影响儿茶酚胺代谢的药物。甲基苯丙胺降低了给予14C-NE的大鼠脑中的NE、脱氨基代谢物和O-甲基化脱氨基代谢物,并显著提高了去甲变肾上腺素。关于DA的代谢,甲基苯丙胺增加了3-甲氧基酪胺和高香草酸,并减少了脱氨基代谢物,但对DA和NE没有影响。另一方面,一种类似利血平的药物(Ro4-1284)在NE代谢中降低了NE,并增加了脱氨基代谢物和O-甲基化脱氨基代谢物,在DA代谢中在很大程度上降低了DA和NE,并增加了高香草酸。从这些结果可以得出结论,甲基苯丙胺对NE代谢的影响比对DA更明显,而Ro4-1284对DA代谢的影响比对NE更明显。

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