Enkephalin: Difference between revisions
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The main and most known effect of enkephalins is analgesia, which makes the therapeutic use of enkephalins to treat pain one their main clinical relevant aspect. However, enkephalins have a relatively low stability ''in-vivo'', due to their degradation by endogenous peptidases <ref name="cullen"/>. Two approaches have been proposed to this issue: the first one is the chemical modification of enkephalins while preserving their analgesic efficacy. One example of this is the design of D-Ala-methionine-enkephalin in 1976 by Pert et al. <ref>Pert, C. B., Pert, A., Chang, J. K., & Fong, B. T. (1976). (D-Ala2)-Met-enkephalinamide: a potent, long-lasting synthetic pentapeptide analgesic. Science (New York, N.Y.), 194(4262), 330–332. https://doi.org/10.1126/science.968485</ref>. Kropotova et al. in 2020 have designed different modified enkephalins that are less accessible to endopeptidases <ref>Kropotova, E. S., Ivleva, I. S., Karpenko, M. N., & Mosevitsky, M. I. (2020). Design of enkephalin modifications protected from brain extracellular peptidases providing long-term analgesia. Bioorganic & medicinal chemistry, 28(1), 115184. https://doi.org/10.1016/j.bmc.2019.115184</ref>. | The main and most known effect of enkephalins is analgesia, which makes the therapeutic use of enkephalins to treat pain one their main clinical relevant aspect. However, enkephalins have a relatively low stability ''in-vivo'', due to their degradation by endogenous peptidases <ref name="cullen"/>. Two approaches have been proposed to this issue: the first one is the chemical modification of enkephalins while preserving their analgesic efficacy. One example of this is the design of D-Ala-methionine-enkephalin in 1976 by Pert et al. <ref>Pert, C. B., Pert, A., Chang, J. K., & Fong, B. T. (1976). (D-Ala2)-Met-enkephalinamide: a potent, long-lasting synthetic pentapeptide analgesic. Science (New York, N.Y.), 194(4262), 330–332. https://doi.org/10.1126/science.968485</ref>. Kropotova et al. in 2020 have designed different modified enkephalins that are less accessible to endopeptidases <ref>Kropotova, E. S., Ivleva, I. S., Karpenko, M. N., & Mosevitsky, M. I. (2020). Design of enkephalin modifications protected from brain extracellular peptidases providing long-term analgesia. Bioorganic & medicinal chemistry, 28(1), 115184. https://doi.org/10.1016/j.bmc.2019.115184</ref>. | ||
The second approach to increase enkephalin stability ''in-vivo'' is the blocking of the peptidases themselves, such as enkephalinase and aminopeptidase. One example is DENKIs <ref name="cullen"/>. | The second approach to increase enkephalin stability ''in-vivo'' is the blocking of the peptidases themselves, such as enkephalinase and aminopeptidase. One example is DENKIs <ref name="cullen"/>.Dual Enkephalinase Inhibitors (DENKIs) are a novel therapeutic approach for opioid use disorders. This class of compounds physiologically activates the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins, increasing their half-lives and physiological actions <ref>Alvarez-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. 2021. Accepted Author Manuscript. https://doi.org/10.1111/bph.15656</ref>. | ||
Dual Enkephalinase Inhibitors (DENKIs) are a novel therapeutic approach for opioid use disorders. This class of compounds physiologically activates the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins, increasing their half-lives and physiological actions <ref>Alvarez-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. 2021. Accepted Author Manuscript. https://doi.org/10.1111/bph.15656</ref>. | |||
== References == | == References == | ||
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