Concentration of Tricyclic Antidepressants in Plasma, Heart and Skeletal Muscle after their Intravenous Infusion to Anaesthetized Rabbits

In order to compare the toxic concentrations of four different tricyclic antidepressants in the heart and plasma, 5 mg/kg of amitriptyline, doxepin, nortriptyline or protriptyline were infused intravenously over 5 min. into anaesthetized rabbits. The concentrations of the antidepressants five minutes after the termination of the infusion were measured by gas chromatography in the plasma, heart ventricles, and femoral muscle. On average, the concentrations in the heart were 40 to 200 times higher than those measured in plasma, the concentration of protriptyline being highest. The heart/plasma concentration ratios were higher for protriptyline and amitriptyline than for nortriptyline and doxepin. The toxicity of the antidepressants correlated neither to their heart concentrations nor to their heart/plasma concentration ratios. It seems that the different acute cardiotoxicity of tricyclic antidepressants cannot be explained by their different concentrations in the plasma or in the heart muscle only, but they seem to have different toxic potencies.