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(-)-司来吉兰结合、作用及代谢的色谱研究

Chromatographic studies on the binding, action and metabolism of (-)-deprenyl.

作者信息

Kalász H, Kerecsen L, Knoll J, Pucsok J

机构信息

Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.

出版信息

J Chromatogr. 1990 Jan 19;499:589-99. doi: 10.1016/s0021-9673(00)97003-1.

Abstract

Serum binding, the effect on striatal dopamine release and the metabolism of (-)-deprenyl [N-methyl-N-propargyl(2-phenyl-1-methyl)ethylammonium chloride], TZ-650 [N-methyl-N-propargyl(2-phenyl)ethylammonium chloride] and J-508 [N-methyl-N-propargyl(indanyl)ammonium chloride] were investigated using various chromatographic methods. A strong interaction between (-)-deprenyl and macroglobulins was found. Deprenyl enhanced the dopamine release from striatal slices of the rat brain and also inhibited the dopamine-DOPAC conversion. Deprenyl analogues showed either smaller or no effect. Hydroxylation of (-)-deprenyl takes place in the para position, in addition to the usual oxidative N-dealkylations, which are known from various metabolic studies on N-substituted phenylalkylamines.

摘要

利用各种色谱方法研究了血清结合情况、对纹状体多巴胺释放的影响以及(-)-司来吉兰[N-甲基-N-炔丙基(2-苯基-1-甲基)乙氯化铵]、TZ-650[N-甲基-N-炔丙基(2-苯基)乙氯化铵]和J-508[N-甲基-N-炔丙基(茚满基)氯化铵]的代谢情况。发现(-)-司来吉兰与巨球蛋白之间存在强烈相互作用。司来吉兰增强了大鼠脑纹状体切片中多巴胺的释放,还抑制了多巴胺向3,4-二羟基苯乙酸(DOPAC)的转化。司来吉兰类似物的作用要么较小,要么没有作用。除了各种对N-取代苯烷基胺的代谢研究中已知的常见氧化N-脱烷基反应外,(-)-司来吉兰还会在对位发生羟基化反应。

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