The effects of imipramine, mianserin and trazodone on the chronotropic, inotropic and coronary vascular responses in the isolated perfused rat heart

1. The cardiovascular effects of the tricyclic antidepressant imipramine and two second generation antidepressants mianserin, a tetracyclic, and trazodone, a triazolopyridine derivative, were investigated in the isolated perfused rat heart. 2. Imipramine caused cardiac slowing and a negative inotropic effect at 2.5 microM after 30 min of perfusion. Conversely mianserin and trazodone had no effect on heart rate at 5 microM with inotropic state remaining above control values after 30 min of perfusion. 3. Varying effects on coronary flow, which appear to correlate well with the documented receptor actions of each drug, were demonstrated. Imipramine caused a decrease in coronary flow at 1.25 and 2.5 microM, followed by an increase at 10 microM. Mianserin decreased coronary flow at all concentrations between 1 and 20 microM. Trazodone elicited a marked elevation in coronary flow over the dose range of 2.5 to 250 microM. 4. The results in this model suggest that although the second generation agents appear to cause less cardiodepression all three agents elicit quantitatively different coronary vascular responses.