Kotake H, Hirai S, Matsuoka S, Kinugawa T, Hasegawa J, Mashiba H
First Department of Internal Medicine, Tottori University, Yonago, Japan.
Arch Int Pharmacodyn Ther. 1987 Sep;289(1):72-81.
The effects of maprotiline and mianserin, tetracyclic antidepressant agents, on membrane potentials and currents of rabbit sinoatrial node cells were studied and compared to those of a tricyclic antidepressant compound, imipramine. Imipramine (10 microM), maprotiline (30 microM) and mianserin (100 microM) significantly decreased the spontaneous rate, the maximum rate of rise and the action potential amplitude. The slope of the diastolic depolarization was also decelerated by these drugs. On the current systems, imipramine (10 microM), maprotiline (10-30 microM) and mianserin (40-100 microM) decreased the slow inward current, the time-dependent potassium outward current and the hyperpolarization-activated inward current. Although all these antidepressant agents have qualitatively similar depressant effects, the inhibitory potency on the electrical activity of sinoatrial node was: imipramine greater than maprotiline greater than mianserin. These electrophysiological observations suggest that tetracyclic antidepressant agents might have less pronounced cardiotoxicity than did tricyclic antidepressants in slow response fibers.
研究了四环类抗抑郁药马普替林和米安色林对兔窦房结细胞膜电位和电流的影响，并与三环类抗抑郁化合物丙咪嗪进行了比较。丙咪嗪（10微摩尔）、马普替林（30微摩尔）和米安色林（100微摩尔）显著降低了自发频率、最大上升速率和动作电位幅度。这些药物还使舒张期去极化斜率减慢。在电流系统方面，丙咪嗪（10微摩尔）、马普替林（10 - 30微摩尔）和米安色林（40 - 100微摩尔）降低了慢内向电流、时间依赖性钾外向电流和超极化激活内向电流。尽管所有这些抗抑郁药在性质上具有相似的抑制作用，但对窦房结电活动的抑制效力为：丙咪嗪大于马普替林大于米安色林。这些电生理观察结果表明，在慢反应纤维中，四环类抗抑郁药的心脏毒性可能比三环类抗抑郁药轻。
