Raiteri M, Del Carmine R, Cervoni A M, Levi G
Eur J Pharmacol. 1979 Aug 15;57(4):407-16. doi: 10.1016/0014-2999(79)90503-x.
Imipramine and mianserin are equipotent inhibitors of noradrenaline (NA) uptake in synaptosomes. However, after in vivo administration, NA uptake was inhibited only in synaptosomes from imipramine-treated rats, suggesting that imipramine, or its metabolite desipramine, binds to the NA carrier in a manner outlasting the preparation of synaptosomes, whereas mianserin is washed away. To evaluate binding to the NA carrier, synaptosomes prelabeled with 3H-NA were pretreated with an antidepressant and the release of 3H-NA was then stimulated with unlabeled NA. Any reduction of release was taken as an indication of binding. Pretreatment with desipramine, but not with imipramine or mianserin, reduced 3H-NA release suggesting that desipramine is responsible for NA uptake inhibition in synaptosomes from imipramine-treated rats. Transformation of tertiary into secondary amines seems to be crucial for binding to the NA carrier, as confirmed by the stronger binding of nortriptyline and chlordesipramine compared to amitryptiline and chlorimipramine, respectively. In contrast, tertiary amines bound more strongly than secondary amines to the serotonin carrier. Adult and 8-day old synaptosomes showed similar binding properties towards imipramine and desipraine.
丙咪嗪和米安色林是突触体中去甲肾上腺素（NA）摄取的等效抑制剂。然而，在体内给药后，仅在丙咪嗪处理的大鼠的突触体中NA摄取受到抑制，这表明丙咪嗪或其代谢产物去甲丙咪嗪以一种在突触体制备后仍持续存在的方式与NA载体结合，而米安色林则被洗脱。为了评估与NA载体的结合，用3H-NA预标记的突触体先用一种抗抑郁药预处理，然后用未标记的NA刺激3H-NA的释放。释放的任何减少都被视为结合的指标。用去甲丙咪嗪预处理可减少3H-NA释放，但用丙咪嗪或米安色林预处理则不然，这表明去甲丙咪嗪是丙咪嗪处理的大鼠突触体中NA摄取抑制的原因。叔胺转化为仲胺似乎对于与NA载体的结合至关重要，这分别通过去甲替林和氯氮平与阿米替林和氯米帕明相比更强的结合得到证实。相反，叔胺与5-羟色胺载体的结合比仲胺更强。成年和8日龄的突触体对丙咪嗪和去甲丙咪嗪表现出相似的结合特性。
