RB101-mediated protection of endogenous opioids: potential therapeutic utility?

Abstract

The endogenous opioids met- and leu-enkephalin are inactivated by peptidases preventing the activation of opioid receptors. Inhibition of enkephalin-degrading enzymes increases endogenous enkephalin levels and stimulates robust behavioral effects. RB101, an inhibitor of enkephalin-degrading enzymes, produces antinociceptive, antidepressant, and anxiolytic effects in rodents, without typical opioid-related negative side effects. Although enkephalins are not selective endogenous ligands, RB101 induces these behaviors through receptor-selective activity. The antinociceptive effects of RB101 are produced through either the mu-opioid receptor alone or through activation of both mu- and delta-opioid receptors; the antidepressant-like and anxiolytic effects of RB101 are mediated only through the delta-opioid receptor. Although little is known about the effects of RB101 on other physiologically and behaviorally relevant peptides, these findings suggest that RB101 and other inhibitors of enkephalin-degrading enzymes may have potential as novel therapeutic compounds for the treatment of pain, depression, and anxiety.

• Authors: Emily M Jutkiewicz
• Journal: CNS drug reviews (CNS Drug Rev) Vol. 13 Issue 2 Pg. 192-205 ( 2007) ISSN: 1080-563X [Print] United States
• PMID: 17627672 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Disulfides
• Enzyme Inhibitors
• Prodrugs
• RB 101
• Phenylalanine
• Enkephalin, Methionine
• Enkephalin, Leucine
• Cholecystokinin
• Aminopeptidases
• enkephalin degrading enzyme

Topics

• Aminopeptidases (drug effects)
• Animals
• Cholecystokinin (drug effects, metabolism)
• Disulfides (pharmacology)
• Enkephalin, Leucine (drug effects, metabolism)
• Enkephalin, Methionine (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Mice
• Phenylalanine (analogs & derivatives, pharmacology)
• Prodrugs
• Rats