Human Opiorphin an Endogenous Inhibitor of Enkephalin-Inactivating Ectopeptidases that Displays Antinociception: A Review

Background: The most important investigations since the first publication on opiorphin, in 2006, are summarized in this review. Opiorphin is a human endogenous pentapeptide (Gln-Arg-Phe-Ser-Arg) which inhibits both the Neutral EndoPeptidase (NEP) and aminopeptidase N (AP-N), protecting enkephalins from degradation by these ectopeptidases, thus activating endogenous enkephalin-related opioid pathways. Objective: In this review we highlight the in vitro and in vivo effects of opiorphin. Results: We examine in detail the structure-activity relationship studies addressed in order to identify the amino acids of opiorphin sequence required to functional interactions with its targets and to design its metabolically stable analogs. The modulation of emotionalrelated behaviors and effects on smooth muscle motility including their resulting therapeutic implication are also analysed. In addition, the in vitro potency of opiorphin and its metabolically stable analogs on opioid receptor binding by enkephalin-related peptides are also summarized. Finally, quantitative or semiquantitative analytical methods of opiorphin on various biological samples are cited. Conclusion: The advantages and difficulties of therapeutic applications of opiorphin peptide and its synthetic derivatives are discussed.