Comparison of the chronotropic responses to tri- and tetracyclic antidepressants in isolated sinoatrial node preparations from the rabbit.

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.