Imipramine inhibits soluble enkephalin-degrading aminopeptidase activity in vitro

Considerable evidence has appeared recently connecting the mechanism of action of some antidepressant drugs with the inhibition of the enzymes responsible for enkephalin degradation. Imipramine in vitro inhibits the enkephalin-degrading aminopeptidase MII and interacts with the enzyme in a mixed competitive-noncompetitive manner. The present work shows that imipramine in vitro also inhibits reversibly soluble enkephalin-degrading aminopeptidase activity in rat brain. Kinetic analysis showed that this enzyme has two different binding sites for the drug, and that imipramine interacts with the enzyme in a mixed noncompetitive-acompetitive way.