An old drug against pain, diacerein, inhibits breakdown of palmitoylethanolamide. This compoundm also known as diacetylrhein, is a slow-acting medicine of the class anthraquinone used to treat joint diseases such as osteoarthritis (swelling and pain in the joints). A 2005 Cochrane review found diacerein to be more effective than placebo in improving pain and slowing the progress of osteoarthritis in the hip and knee.
Palmitoylethanolamide (PEA) is produced by mammalian cells from the compound N-palmitoyl-phosphatidyl-ethanolamine, and inactivated by enzymatic hydrolysis to palmitic acid and ethanolamine.
Both fatty acid amide hydrolase-1 (FAAH) and the N-acylethanolamine-hydrolyzing acid amidase (NAAA) catalyzes the hydrolysis of PEA and thus limit its analgesic and anti-inflammatory action of PEA.
The authors report the finding of a new potential inhibitor of NAAA, EPT4900 (4,5-diacetyloxy-9,10-dioxo-anthracene-2-carboxylic acid, also known as the old drug diacerein).
Diacerein exhibited a high inhibitory activity on human recombinant NAAA over-expressed in certain cell-systems. It selectively increased the levels of PEA in such cells, and inhibited inflammation as well as hyperalgesia in mice treated with an intraplantar injection of carrageenan.
This latter effect was accompanied by elevation of PEA endogenous levels in the paw skin.
Old drugs such as diacerein might work via the elevation of endogenous PEA.
Fidelix TS, Soares BG, Trevisani VF (2006). Fidelix, Tania S.A., ed. “Diacerein for osteoarthritis”. Cochrane database of systematic reviews (Online) (1): CD005117. doi:10.1002/14651858.CD005117.pub2. PMID 16437519.