Eto K, Fukuda T, Araki Y, Inoue B, Ogata M
Acta Med Okayama. 1985 Aug;39(4):289-95. doi: 10.18926/AMO/31500.
The effects of tricyclic drugs (clomipramine, imipramine, chlorpromazine and promethazine) on isolated liver mitochondria of rats were examined. All the drugs tested accelerated state 4 respiration. Their stimulative potency at concentrations below 100 microM was in the order of chlorpromazine greater than clomipramine greater than imipramine, promethazine. On state 3 respiration, the chlorine containing drugs had an inhibitive effect at high concentrations, while the other drugs seemed to have a slightly stimulative effect. These drugs stimulated latent ATPase activity of mitochondria. Clomipramine and chlorpromazine inhibited 2, 4-dinitrophenol-stimulated ATPase activity in a dose-dependent fashion. Imipramine also inhibited 2, 4-dinitrophenol-stimulated ATPase activity at high concentrations. Promethazine, however, had almost no effect. All the drugs induced potassium release from mitochondrial vesicles, and their potency was in the order of clomipramine greater than chlorpromazine greater than imipramine greater than promethazine. These results suggest that clomipramine, imipramine, chlorpromazine and promethazine cause impediments in both mitochondrial respiration and ion compartmentation, and that the chlorine containing drugs are more toxic than others on the functions of the mitochondrial membrane.
研究了三环类药物（氯丙咪嗪、丙咪嗪、氯丙嗪和异丙嗪）对大鼠离体肝线粒体的影响。所有测试药物均加速了状态4呼吸。在浓度低于100微摩尔时，它们的刺激效力顺序为氯丙嗪＞氯丙咪嗪＞丙咪嗪、异丙嗪。关于状态3呼吸，含氯药物在高浓度时有抑制作用，而其他药物似乎有轻微的刺激作用。这些药物刺激了线粒体的潜在ATP酶活性。氯丙咪嗪和氯丙嗪以剂量依赖的方式抑制2,4-二硝基苯酚刺激的ATP酶活性。丙咪嗪在高浓度时也抑制2,4-二硝基苯酚刺激的ATP酶活性。然而，异丙嗪几乎没有影响。所有药物均诱导线粒体囊泡释放钾，其效力顺序为氯丙咪嗪＞氯丙嗪＞丙咪嗪＞异丙嗪。这些结果表明，氯丙咪嗪、丙咪嗪、氯丙嗪和异丙嗪在线粒体呼吸和离子分隔方面均造成阻碍，且含氯药物对线粒体膜功能的毒性比其他药物更大。
