Effect of imipramine on enkephalin-degrading peptidases

In recent years, there has been increasing evidence of the involvement of the endogenous opioid system in mental depression and its treatment. In this work, we have measured the effect of imipramine on enkephalin-degrading peptidases in several rat brain areas. Aminopeptidase activities have been assayed using Tyr-beta-naphthylamide as substrate and puromycin as selective inhibitor. Dansyl-D-Ala-Gly-Phe(pNO2)-Gly has been the substrate for neutral endopeptidase 24.11. Imipramine in vitro inhibits puromycin-sensitive activities in all brain areas studied, without affecting the rest of the enzymes assayed. However, subacute imipramine treatment increases neutral endopeptidase activity in the hypothalamus and chronic treatment increases this activity in the hypothalamus and the striatum. These results suggest to us that enkephalin-degrading peptidases are involved in the acute and chronic action mechanism of imipramine and reinforce the idea that the central enkephalinergic activity is dynamically changed during the treatment of depressive illness.