N-(2-hydroxyethyl)hexadecanamide (PEA) against activated mast cells

N-(2-hydroxyethyl)hexadecanamide is a somewhat less used name of palmitoylethanolamide (PEA). Professor Levi-Montalcini discovered the mechanism of PEA related to its inhibitory effects on activated mast cells, a kind of inflammation cells inducing inflammation and pain. She also explained that PEA counteracts NGF, a pro-inflammatory growth factor.

In the paper of her students in 1996 Mazzari et al pointed out that mast cells play a key role in inflammatory reactions triggered by tissue injury or immune activation. The endogenous molecule capable of modulating inappropriate mast cell activity discussed was N-(2-Hydroxyethyl)hexadecanamide (palmitoylethanolamide). PEA at that time was already found in peripheral tissues, and was been proposed to act as a local autacoid capable of negatively regulating mast cell activation and inflammation-hence the acronym posed by Levi-Montalcini: Autacoid Local Inflammation Antagonism (ALIA).

The authors described experiments using pure PEA under the code name LG 2110/1.

In their paper they characterized and functionally correlated the anti-inflammatory actions of PEA with its ability to control mast cell activation, when given orally in a battery of rodent models of inflammation. The results showed PEA has clear effects when administered orally: inflammation diminished, in a dose-dependent and correllated manner, as well did the number of degranulated mast cells and plasma extravasation induced by substance P injection in the mouse ear pinna. ( a specific inflammation  model).

They also described PEA to reduce dose dependently plasma extravasation induced by passive cutaneous anaphylaxis reaction.

In adult rats model PEA decreased, in a dose-dependent manner, carrageenan-induced hindpaw edema and hyperalgesia, also signs of pain and inflammation.

Further, anti-edema effects were observed when utilizing dextran and formalin, known to also cause mast cell activation.

Locally administered PEA was likewise effective in minimizing dextran-induced hind paw edema.

They concluded:

These results indicate that orally administered N-(2-hydroxyethyl)hexadecanamide (PEA) is effective in:

(a) directly down-modulating mast cell activation in vivo;

(b) suppressing pathological consequences initiated by mast cell activation independently of the activating stimuli;

(c) exerting an anti-inflammatory action distinguishable from that of classical steroidal and non-steroidal anti-inflammatory agents.

…PEA represent a novel therapeutic agents useful in the management of inflammatory disease conditions.


Mazzari S, Canella R, Petrelli L, Marcolongo G, Leon A. N-(2-hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. Eur J Pharmacol. 1996 Apr 11;300(3):227-36.

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