Description
Palmitoylethanolamide (PEA) is a fatty acid amide produced in the body that binds to and activates the peroxisome proliferator-activated receptor alpha (PPAR-α). It was initially described as an agonist to the type 2 cannabinoid receptor (CB2), though it is now recognized that PEA does not bind to cannabinoid receptors. PEA is known to have anti-inflammatory, analgesic, and neuroprotective properties. PEA supplements have been used by people with chronic pain as well as those with neuropathic pain.
Chemical Properties
Palmitoylethanolamide is a natural occurring lipid belonging to the class of autacoids. It is a fine white to yellow powder. PEA consists of palmitic acid and ethanolamine. It is the hydrolyzed form of N-(2-hydroxyethyl)-palmitamide, a crystalline structure isolated in soy lecithin. It is this hydrolyzed substance that accounts for the anti-inflammatory properties that were first noted by scientists in 1957. PEA's effects on the immune system have been studied since 1939.
Uses
Palmitoylethanolamide is a natural substance produced by the body and it is very effective and safe to use as a supplement for pain and reduce inflammation.
PEA can be synthesized within the human body from the abundant fatty acid palmitic acid, but it is not dependent or influenced by dietary consumption of fatty acids. Palmitic acid in the diet is derived from dairy products such as cheese and butter, palm tree oil, and animal meat products. However, increasing palmitic acid in the hope of increasing endogenous PEA synthesis will not be effective.
The anti-inflammatory properties of PEA are due to its ability to inhibit inflammation-causing proteins called cytokines. Cytokines are released during periods of inflammation. PEA can suppress the secretion of tumor necrosis factor alpha (TNF alpha), a cytokine, while also inhibiting the release of interleukins. Interleukins are a specific class of cytokines which belong in the immunological system and are activated during the process of inflammation.
Chronic Pain and the Use of Palmitoylethanolamide: An Update
Definition
ChEBI: Palmitoylethanolamide is an N-(long-chain-acyl)ethanolamine that is the ethanolamide of palmitic (hexadecanoic) acid. It has a role as an anti-inflammatory drug, an antihypertensive agent, a neuroprotective agent and an anticonvulsant. It is a N-(long-chain-acyl)ethanolamine, an endocannabinoid and a N-(saturated fatty acyl)ethanolamine. It is functionally related to a hexadecanoic acid.
Biological Functions
Palmitoylethanolamide (PEA) is a fatty acid amide molecule involved in a variety of cellular functions in chronic pain and inflammation. It has been shown to have neuroprotective, anti-inflammatory, anti-nociceptive (antipain) and anti-convulsant properties. Often in people with chronic disorders, the body does not produce enough PEA, which causes problems.
Taking PEA to supplement the body’s shortage is may be beneficial if you have chronic and neuropathic pain and inflammation, as has been demonstrated in clinical trials. These include peripheral neuropathies such as diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis, chronic regional pain syndrome, chronic pelvic pain, postherpetic neuralgia, and vaginal pains.
Flammability and Explosibility
Not classified
Biological Activity
Palmitoylethanolamide (PEA) is a natural fatty acid amide of ethanolamine and palmitic acid. It is found in soybeans, egg yolk, and many other food sources. PEA is an endogenous cannabinoid receptor agonist. It is a peroxisome proliferator-activated receptor α (PPAR-α) ligand. PEA possesses anti-inflammatory, anti-allergic, neuroprotective, and analgesic activities. It belongs to the class of lipid mediators and the N-acylethanolamine family. PEA blocks the release of pro-inflammatory mediators from activated mast cells and prevents the recruitment of activated mast cells at the site of nerve injury.
Side effects
There are no known problematic side-effects. PEA can be taken together with any other substance. It enhances the pain-relieving effect of classic analgesics and anti-inflammatories. Palmitoylethanolamide can be used in combination with other substances without any side effects.
ARE THERE ANY SIDE EFFECTS
Synthesis
1) Under nitrogen protection, triethylamine (2 mL) was slowly added dropwise to a reaction vessel containing mercaptomethyl resin (2 g, MATRIX-INN), N-hydroxymaleimide (1.1 g, 9.7 mmol) and DMF (40 mL). After stirring at room temperature for 24 hours, the temperature was raised to 55°C and stirring was continued for 4 hours. The reaction mixture was cooled to room temperature and filtered, and the resulting NHS resin was washed twice each with DMF, distilled water and isopropanol sequentially, and dried under vacuum.
2) Palmitic acid (1.465 g, 5.72 mmol), NHS resin (1.50 g) prepared above, DIC (diisopropylcarbodiimide, 0.72 g, 5.72 mmol) and triethylamine (2 mL) were suspended in dichloromethane (15 mL). After stirring for 4 h at room temperature, the filtrate was filtered and retained for subsequent reactions (the amount of palmitic acid, DIC and solvent in the filtrate was detected by HPLC). The resin was washed twice each with DMF, water, isopropanol and dichloromethane sequentially, and dried under vacuum to obtain 1.70 g of dried resin with a loading of 1.0 mmol/g of immobilized palmitic acid active ester.
3) Ethanolamine (93.2 mg, 1.58 mmol) was added to a flask containing the activated ester (1.75 g) and 50 mL of ethanol, and suspended and stirred for 0.5 hr. The solid resin was removed by centrifugation and the resin was washed twice with ethanol (the resin was vacuum dried after washing). The liquid phases were combined and concentrated under reduced pressure to give 453 mg of palmitic acid monoethanolamide in 96.6% yield and >99.5% purity (HPLC detection).
References
[1] Beilstein Journal of Organic Chemistry, 2009, vol. 5,
[2] Patent: CN107188816, 2017, A. Location in patent: Paragraph 0048-0052
[3] Chemistry and Physics of Lipids, 2012, vol. 165, # 7, p. 705 - 711
[4] Patent: WO2015/179190, 2015, A1. Location in patent: Paragraph 0137
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 3231 - 3234
