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
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.