If true, this concept would support a potential therapeutic use of enkephalinase
inhibitors (DENKIs), which have been developed to increase the half-lives and extracellular concentrations of enkephalins, in the treatment of chronic pain .
It has been also hypothesized that the ACE protease inhibitor might block the enzyme enkephalinase
that is important in the breakdown of enkephalins, with potential effects on behaviours [15, 16].
Pharmaleads present results of the first Dual ENKephalinase
Inhibitors (DENKIs) to reach the clinic
Neprilysin (NEP)  (neutral endopeptidase, enkephalinase
, E.C.24.11) was discovered from rabbit kidney proximal tubule brush border membranes by Kerr and coworkers (1).
Roques, "Autoradiographic comparison of the distribution of the neutral endopeptidase "enkephalinase
" and of mu and delta opioid receptors in rat brain," Proceedings of the National Academy of Sciences of the United States of America, vol.
Neutral endopeptidase, also known as neprilysin (NEP), CD10, membrane metalloendopeptidase (MME), enkephalinase
, or common acute lymphoblastic leukemia antigen (CALLA), is a zinc-dependent type II integral membrane peptidase EC 188.8.131.52.
Racecadotril, an oral enkephalinase
inhibitor was used in the treatment of acute diarrhea by some researchers based on the principle that it prevents the degradation of endogenous opioids (Enkephalins) responsible for hypersecretion of water and electrolytes into intestinal lumen.
Smith, "Amelioration of naloxone-precipitated opioid withdrawal symptoms by peripheral administration of the enkephalinase
inhibitor acetorphan," Psychopharmacology, vol.
Malfroy et al., "'Enkephalinase
', a newly characterised dipeptidyl carboxypeptidase: properties and possible role in enkephalinergic transmission," International Journal of Neurology, vol.
(Indianapolis, IN) included amino acid precursors such as L-phenylalanine, l-tyrosine, L-tryptophan, 5-hydroxytryptophane, L-glutamine, a serotonin concentrating substance chromium, an enkephalinase
inhibitor D-phenylalanine, a neurotransmitter synthesis promoter vitamin B6, as well as both methionine and leucine.
It is thought that phenylalanine also serves to promote enkephalin activity, by acting as an enkephalinase
25 November 2011 - Pharmaleads, a French company developing small protease inhibiting molecules for diagnostic and therapeutic use, on Thursday announced positive data from two Phase I trials on PL37, its first molecule and lead compound of a new class of painkillers, Dual ENKephalinase