Álvarez-Pérez, BeltránPoras, HervéMaldonado, Rafael, 1961-2022-01-142022-01-142023Alvarez-Perez B, Poras H, Maldonado R. The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders. Br J Pharmacol. 2023;180(7):879-93. DOI: 10.1111/bph.156560007-1188http://hdl.handle.net/10230/52218Despite the increasing impact of opioid use disorders on society, there is a disturbing lack of effective medications for their clinical management. An interesting innovative strategy to treat these disorders consists in the protection of endogenous opioid peptides to activate opioid receptors, avoiding the classical opioid-like side effects. Dual enkephalinase inhibitors (DENKIs) physiologically activate the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins and increasing their half-lives and physiological actions. The activation of opioid receptors by the increased enkephalin levels, and their well-demonstrated safety, suggests that DENKIs could represent a novel analgesic therapy and a possible effective treatment for acute opioid withdrawal, as well as a promising alternative to opioid substitution therapy minimizing side effects. This new pharmacological class of compounds could bring effective and safe medications avoiding the major limitations of exogenous opioids, representing a novel approach to overcome the problem of opioid use disorders.application/pdfeng© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/bph.15656Aminopeptidase NDual enkephalinase inhibitorNeprilysinOpioidOpioid use disordersδ-opioid receptorμ-opioid receptorinfo:eu-repo/semantics/openAccess