Potent N-acylethanolamine acid amidase (NAAA) inhibitors are looked for

Potent N-acylethanolamine acid amidase (NAAA) inhibitors are looked for by pharmaceutical industry. N-Acylethanolamine acid amidase (NAAA) is a lysosomal cysteine hydrolase involved in the degradation of saturated and monounsaturated fatty acid ethanolamides (FAEs), a family of endogenous lipid agonists of peroxisome proliferator-activated receptor-α, which include oleoylethanolamide (OEA) and palmitoylethanolamide (PEA).

Such potent inhibitors of NAAA would create higher levels of endogenous compounds such as PEA, and thus have a analgesic and anti-inflammatory action. The lysosomal enzyme referred to as N-acylethanolamine-hydrolyzing acid amidase (NAAA) catalyzes the same reaction with preference to palmitoylethanolamide, an endogenous analgesic and neuroprotective substance, and is therefore expected as a potential target of therapeutic drugs.

However, history has learned that inhibiting enzymes has many unwanted side effects.

Therefore it is much more valuable to supplement with PEA and OEA, natural fatty amides via food or supplements. The same effects can be generated without side effects of unnatural enzyme inhibition.

The search for NAAA inhibitors has been driven mainly if not exclusively by patent protection and money generation…

Ponzano S, Bertozzi F, Mengatto L, Dionisi M, Armirotti A, Romeo E, Berteotti A, Fiorelli C, Tarozzo G, Reggiani A, Duranti A, Tarzia G, Mor M, Cavalli A, Piomelli D, Bandiera T. Synthesis and structure-activity relationship (SAR) of 2-methyl-4-oxo-3-oxetanylcarbamic acid esters, a class of potent N-acylethanolamine acid amidase (NAAA) inhibitors. J Med Chem. 2013 Sep 12;56(17):6917-34. doi: 10.1021/jm400739u. Epub 2013 Aug 30.

Taylor BK. N-acylethanolamine acid amidase (NAAA), a new path to unleash PPAR-mediated analgesia. Pain. 2013 Mar;154(3):326-7. doi: 10.1016/j.pain.2012.12.012. Epub 2012 Dec 28.

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