Ishikawa K, Shibanoki S, Kubo T, Watabe S, Matsumoto A, Kogure M
Eur J Pharmacol. 1986 Jan 14;120(1):63-8. doi: 10.1016/0014-2999(86)90640-0.
A comparative study of the ability to block the amine pump was carried out on tricyclic antidepressants including dothiepin and northiaden in vivo. Dothiepin was found to prevent the 6-OHDA-induced depletion of cardiac noradrenaline but not the PCA-induced depletion of intracerebral serotonin. Northiaden, an active metabolite of dothiepin, also possessed the same ability with a greater potency than the parent drug. Neither compound affected the biosynthesis of catecholamines and indoleamine. However, neither dothiepin nor northiaden affected 5-HT uptake, as was also observed with imipramine and amitriptyline. These results suggest that the clinical efficacy of dothiepin may be due to inhibition of the amine pump, especially of the catecholamine uptake mechanism, which is qualitatively the same as for imipramine and amitriptyline.
在体内对包括多塞平及去甲替林在内的三环类抗抑郁药的胺泵阻断能力进行了一项对比研究。研究发现，多塞平可预防6-羟基多巴胺诱导的心脏去甲肾上腺素耗竭，但不能预防对氯苯丙氨酸诱导的脑内5-羟色胺耗竭。多塞平的活性代谢产物去甲替林也具有相同能力，且效力比母体药物更强。两种化合物均不影响儿茶酚胺和吲哚胺的生物合成。然而，多塞平及去甲替林均不影响5-羟色胺摄取，丙咪嗪和阿米替林也有同样的情况。这些结果表明，多塞平的临床疗效可能归因于对胺泵的抑制，尤其是对儿茶酚胺摄取机制的抑制，这在性质上与丙咪嗪和阿米替林相同。
