The introduction in one of the hall mark papers of the history of palmitoylethanolamide: a study published in 1959, conducted with pure PEA were the investigators clearly demonstrated the biological activity of PEA as an anti-inflammatory drug. It would need many more years before professor Levi-Montalcini discovered the reason for the anti-inflammatory action of PEA (in 1993). SEVERAL investigators have indicated that extracts of egg yolk, peanut oil, and soybean lecithin have anti-inflammatory activity.
Purification of these anti-inflammatory extracts was achieved, and in each case the active agent was identified as N (2-hydroxyethyl) palmitamide (palmitoylethanolamide).
This compound was assayed in the guinea pig by measuring reduction of swelling induced in joints by an antigen-antibody reaction. Swelling was reduced about 60 per cent at low concentrations (3 gamma per kilogram), and tuberculin reaction in the guinea pig was inhibited.
On the other hand, no activity was found by several other types of assays employed to measure anti-inflammatory activity.
The findings in the guinea pig prompted us to investigate the effect of ethanolamine palmitamide and related compounds on systemic anaphylaxis and on serotonin and histamine toxicity in the mouse.
The result of their findings was:
The effect of N (2-hydroxyethyl) palmitamide, ethanolamine hydrochloride,
and a variety of fatty acids on passive anaphylaxis, serotonin, and histamine
toxicity in the mouse was studied. The above compounds were found to be
active in suppressing anaphylaxis and serotonin toxicity at low concentrations
(about 5 mg. per kilogram), but they were shown to have no effect on histamine
toxicity. Data presented indicate that fatty acids can act as potent pharmaco-
In 1960 Coburn would summerize the states of PEA:
Experimental findings clearly indicate that there is at least one antianaphylactic substance in egg-yolk alcoholsoluble material, which appears to be absent from the protein or acetone-soluble material (Coburn et al. 1954). This finding has been confirmed and extended in several laboratories by measuring joint and skin lesions in either the Arthus or tuberculin reaction.
French and Allen (1955) showed that the reverse Arthus reaction could be used successfully to demonstrate the anti-inflammatory effects of egg-yolk phospholipid fractions. Chang and French (1956) found that the active material was in the A.S.M., absent from the protein and acetone-soluble fractions, and that the anti-inflammatory effect did not appear to be mediated by the adrenals. Following the important work of Long and Martin (1956), Kuehl et al. (1957) identified in egg yolk N-(2-hydroxyethyl)-palmitamide as a natural occurring anti-inflammatory agent. Later, Ganley and his associates (1958) in a wide variety of tests studied the anti-inflammatory activity of compounds obtained from egg yolk, peanut oil, and soybean oil. Their crystalline fractions from three sources were all identified as N-(2-hydroxyethyl)-palmitamide. They were active (antianaphylactic) at 0-3 /g. per kg. body-weight.
( The concept of egg yolk as a dietary inhibitor to rheumatic susceptibility. COBURN AF. Lancet. 1960 Apr 16;1(7129):867-70.)
Oswald H. Ganley, Ph.D., and Harry J. Robinson, Ph.D., M.D., Rahway, N. J. ANTI-ANAPYLACTIC AND ANT’I-SEROTONIN ACTIVITY OF A COMPOUND OBTAINED FROM EGG YOLK, PEANUT OIL, AND SOYBEAN LECITHIN (From the Merck Institute for Therapeutic Research) 1959.
The effect of N-(2-hydroxyethyl)-palmitamide on delayed hypersensitivity in guinea-pig. by Perlík F, Krejcí J, Elis J, Pekárek J, Svejcar J.in: Experientia. 1973 May 1;29(1):67-8. No abstract available.
- Anti-inflammatory properties of N(2-hydroxyethyl) palmitamide. by Perlík F, Rasková H, Elis J. Acta Physiol Acad Sci Hung. 1971;39(4):395-400.