Enkephalins peptidase inactivation

Some drugs possessing amide bonds, such as prilocaine, and of course, peptides, can be hydrolyzed by peptidases and inactivated in this manner. Peptidases are also of pharmacological interest because they are responsible for the formation of highly reactive cleavage products (fibrin, p. 146) and potent mediators (angiotensin 11, p. 124 bradykinin, enkephalin, p. 210) from biologically inactive peptides. 

PEPTIDASE-DEPENDENT INACTIVATION OF ENKEPHALINS DESIGN OF DUAL INHIBITORS OF NEP/APN... 

Owing to the complementary roles of NEP and APN in enkephalin inactivation, selective inhibitor of only one of the two peptidases gives weak antinoceptive effects even after ICV administration. This led us to propose the concept of mixed inhibitors, that is, compounds able to simultaneously block NEP and APN activities [reviews in 9,20]. This was possible owing to the fact that these two membrane-bound enzymes belong to the superfamily of zinc metallopeptidases. 

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