Although its presence in mammalian tissues has been known since the 1960s, N-palmitoyl-ethanolamine (PEA) has emerged only recently among other bioactive N-acylethanolamines as an important local pro-homeostatic mediator which, due to its chemical stability, can be also administered exogenously as the active principle of current anti-inflammatory and analgesic preparations (e.g. Normast, Pelvilen). Much progress has been made towards the understanding of the mechanisms regulating both the tissue levels of PEA under physiological and pathological conditions, and its pharmacological actions. Here we review these new developments in PEA biochemistry and pharmacology, and discuss novel potential indications for the therapeutic use of this compound and of synthetic tools that selectively retard its catabolism, such as the inhibitors of the recently cloned N-acylethanolamine-hydrolyzing acid amidase.

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