Inhibition of uptake of catecholamines by benzylamine derivatives.
Inhibition of uptake of catecholamines by benzylamine derivatives.
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苄胺衍生物抑制儿茶酚胺的摄取。
DOI：
10.1021/jm00190a004
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发表时间：
1979
影响因子：
7.3
通讯作者：
A. Cho
中科院分区：
文献类型：
--
作者：
R. Kammerer;B. Amiri;A. Cho
合成了8个苄胺类化合物，包括N-(2-氯乙基)-N-乙基-2-甲基苄胺(5)，并评价了它们对去甲肾上腺素和多巴胺在大鼠脑匀浆中蓄积的抑制作用。所有化合物对皮层中去甲肾上腺素的抑制作用比对纹状体中多巴胺的抑制作用低得多。高效性(低I50)和高特异性(与多巴胺转运相比，更倾向于抑制去甲肾上腺素的转运)与(2-氯乙基)部分、叔氨基中心和苯氨基中芳香族功能的邻位取代有关。5也可抑制兔主动脉对去甲肾上腺素的摄取，表明其对摄取过程有一定的抑制作用。在共孵育研究中，与适当的对照相比，可卡因可防止5的影响，表明5作用于可卡因的作用部位或靠近可卡因的作用部位，被认为是摄取载体部位。
Eight benzylamine analogues of bretylium were synthesized, including N-(2-chloroethyl)-N-ethyl-2-methylbenzylamine (5), and evaluated as inhibitors of accumulation of norepinephrine and dopamine in rat brain homogenates. All compounds gave an I50 value (concentration of inhibitor that causes 50% reduction in control accumulation) considerably lower against norepinephrine in cortex that against dopamine in striatum. High potency (low I50) and high specificity (preference for inhibition of norepinephrine transport compared to dopamine transport) are associated with a (2-chloroethyl) moiety, tertiary amino center, and ortho substitution of the aromatic function in the benzylamino group. 5 also inhibited the uptake of norepinephrine in rabbit aorta, indicating its effect against the uptake process in general. Cocaine protects against the effects of 5 in coincubation studies when compared to the appropriate controls, indicating that 5 acts at or close to the site of action of cocaine which is thought to be the uptake carrier site.