Relative toxicity of amitriptyline, imipramine, maprotiline and mianserin in acute experiments in rabbits

Summary

In conscious rabbits, a slow intravenous infusion of amitriptyline, imipramine, maprotiline or mianserin produced death preceded by convulsions. Amitriptyline produced these effects at the lowest dose, imipramine and maprotiline were intermediate and much higher doses of mianserin were required. Cardiac dysrhythmias in the form of missing QRS complexes were evident in 6 out of 6 animals receiving amitriptyline, 6/6 with maprotiline and 2/6 with imipramine but were not seen in animals receiving mianserin. All four drugs lengthened the P-R interval and widened the QRS complex, though these effects were smallest with mianserin. The convulsive episodes greatly modified cardiovascular parameters and therefore complicated an assessment of cardiovascular toxicity. No convulsive episodes developed in barbiturate-anaesthetized rabbits infused with the antidepressants and heart rate and blood pressure were lowered by all four drugs. The P-R interval was lengthened and the QRS complex increased in width; these effects were greatest with amitriptyline and least with mianserin, which was up to 30-times less effective than amitriptyline in causing cardiovascular disturbances. Dysrhythmias were seen with all four drugs, but only at very high doses with mianserin. In these models it is concluded that the relative cardiovascular toxicity of these antidepressants is in the order amitriptyline > imipramine > maprotiline ≫ mianserin.

Key Words::

• Amitriptyline
• imipramine
• maprotiline
• mianserin
• antidepressive agents
• antidepressive agents
• tricyclic