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|Section1= |Section2= |Section3= |Section4= }} Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists. PEA has been demonstrated to bind to a receptor in the cell-nucleus (a nuclear receptor) and exerts a great variety of biological functions related to chronic pain and inflammation. The main target is thought to be the peroxisome proliferator-activated receptor alpha (PPAR-α). PEA also has affinity to cannabinoid-like G-coupled receptors GPR55 and GPR119. PEA cannot strictly be considered a classic endocannabinoid because it lacks affinity for the cannabinoid receptors CB1 and CB2. However, the presence of PEA (and other structurally related N-acylethanolamines) has been known to enhance anandamide activity by a so-called "entourage effect". Several papers have demonstrated that an imbalance of the endocannabinoid system (ECS) and alterations in the levels of PEA occur in acute and chronic inflammation. For instance during β-amyloid-induced neuroinflammation the deregulation of cannabinoid receptors and its endogenous ligands accompanies the development and progression of disease. PEA has been shown to have anti-inflammatory,〔 anti-nociceptive, neuroprotective, and anticonvulsant properties. ==Early studies== Indications as anti-inflammation and analgesia stem from before 1980, and the birth of the molecule was in 1957. In that year 5 researchers from MSD described N-(2-hydroxyethyl)-palmitamide, as they called the molecule at that time, as a natural anti-inflammatory agent. They stated: ''" We have succeeded in isolating a crystalline anti-inflammatory factor from soybean lecithin and identifying it as (''S'')-(2-hydroxyethyl)-palmitamide. The compound also was isolated from a phospholipid fraction of egg yolk and from hexane-extracted peanut meal."'' In 1975 Czech physicians described the result of a clinical trial in joint pain in ''The Lancet''. The analgesic action of 3 grams of aspirin during the day was compared to PEA 1.8 gram/day. Both drugs were reported to enhance joint movements and decrease pain. In 1970 the pharmaceutical industry Spofa introduced Impulsin, tablets of 500 mg PEA for the treatment and prophylaxis of flu and respiratory infections in Czechoslovakia, and the company Almirall introduced Palmidrol, as tablets and as a suspension in Spain in 1976 for the same indication. In the 1990s, the relation between anandamide and PEA was described, and the expression of receptors sensitive for those two molecules on mast cells was first demonstrated by the group of Nobel prize winner Rita Levi-Montalcini. In this period more insight into the function of the endogenous fatty acid derivatives emerged, and compounds such as oleamide, palmitoylethanolamide, 2-lineoylglycerol, 2-palmitoylglycerol were explored for their capacity to modulate pain sensitivity and inflammation via what at that time was thought to be, the endocannabinoid signalling pathway. One group demonstrated that PEA could alleviate, in a dose-dependent manner, pain behaviors elicited in mice-pain models and could downregulate hyperactive mast cells.〔 PEA and related compounds such as anandamide also seem to have synergistic effects in models of pain and analgesia. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Palmitoylethanolamide」の詳細全文を読む スポンサード リンク
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