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Hub AI
Palmitoylethanolamide AI simulator
(@Palmitoylethanolamide_simulator)
Hub AI
Palmitoylethanolamide AI simulator
(@Palmitoylethanolamide_simulator)
Palmitoylethanolamide
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, and lipid modulator.
A main target of PEA is proposed 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.
In 1975, Czech physicians described the results of a clinical trial[clarification needed] looking at joint pain, where the analgesic action of aspirin versus PEA was tested; both drugs were reported to enhance joint movements and decrease pain. In 1970 the drug manufacturer Spofa in Czechoslovakia introduced Impulsin, a tablet dose of PEA, for the treatment and prophylaxis of influenza and other respiratory infections.[citation needed] In Spain, the company Almirall introduced Palmidrol in tablet and suspension forms in 1976, for the same indications.[citation needed]
In the mid-1990s, the relationship between anandamide and PEA was described;[non-primary source needed] the expression of mast cell receptors sensitive to the two molecules was demonstrated by Levi-Montalcini and coworkers.[according to whom?][non-primary source needed] During this period, more insight into the functions of endogenous fatty acid derivatives emerged, and compounds such as oleamide, palmitoylethanolamide, 2-lineoylglycerol and 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.
Primary reports also have provided evidence that PEA downregulates hyperactive mast cells in a dose-dependent manner, and that it alleviates pain elicited in mouse models.[verification needed] PEA and related compounds such as anandamide also seem to have synergistic effects in models of pain and analgesia.
In a variety of animal models, PEA seems to have some promise;[editorializing][citation needed] researchers have been able to demonstrate relevant clinical efficacy in a variety of disorders, from multiple sclerosis to neuropathic pain.
In the mouse forced swimming test, palmitoylethanolamide was comparable to fluoxetine for depression. An Italian study published in 2011 found that PEA reduced the raised intraocular pressure of glaucoma. In a spinal trauma model, PEA reduced the resulting neurological deficit via the reduction of mast cell infiltration and activation. PEA in this model also reduced the activation of microglia and astrocytes. Its activity as an inhibitor of inflammation counteracts reactive astrogliosis induced by beta-amyloid peptide, in a model relevant for neurodegeneration, probably via the PPAR-α mechanism of action.[verification needed] In models of stroke and other CNS trauma, PEA exerted neuroprotective properties.
Chronic pain and neuropathic pain are indications for which there is high unmet need in the clinic. PEA has been tested in a variety of animal models for chronic and neuropathic pain, because cannabinoids, such as THC, have been proven to be effective in neuropathic pain states. The analgesic and antihyperalgesic effects of PEA in two models of acute and persistent pain seemed to be explained at least partly via the de novo neurosteroid synthesis. In chronic granulomatous pain and inflammation model, PEA could prevent nerve formation and sprouting, mechanical allodynia, and PEA inhibited dorsal root ganglia activation, which is a hallmark for winding up in neuropathic pain. The mechanism of action of PEA as an analgesic and anti-inflammatory molecule is probably based on different aspects.[editorializing][citation needed] PEA inhibits the release of both preformed and newly synthesised mast cell mediators, such as histamine and TNF-alpha. PEA, as well as its analogue adelmidrol (di-amide derivative of azelaic acid), can both down-regulate mast cells. PEA reduces the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and prevents IkB-alpha degradation and p65 NF-kappaB nuclear translocation, the latter related to PEA as an endogenous PPAR-alpha agonist. In 2012 it became clear that PEA can also reduce reperfusion injury and the negative impact of shock on various outcome parameters, such as renal dysfunction, ischemic injury and inflammation, most probably via the PPAR-alpha pathway.[editorializing][citation needed] Studies have shown that PEA activates PPAR-alpha and TRPV1 receptors that control inflammation and the sensation of pain. Among the reperfusion and inflammation markers measured PEA could reduce the increase in creatinine, γGT, AST, nuclear translocation of NF-κBp65; kidney MPO activity and MDA levels, nitrotyrosine, PAR and adhesion molecules expression, the infiltration and activation of mast cells and apoptosis.
Palmitoylethanolamide
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, and lipid modulator.
A main target of PEA is proposed 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.
In 1975, Czech physicians described the results of a clinical trial[clarification needed] looking at joint pain, where the analgesic action of aspirin versus PEA was tested; both drugs were reported to enhance joint movements and decrease pain. In 1970 the drug manufacturer Spofa in Czechoslovakia introduced Impulsin, a tablet dose of PEA, for the treatment and prophylaxis of influenza and other respiratory infections.[citation needed] In Spain, the company Almirall introduced Palmidrol in tablet and suspension forms in 1976, for the same indications.[citation needed]
In the mid-1990s, the relationship between anandamide and PEA was described;[non-primary source needed] the expression of mast cell receptors sensitive to the two molecules was demonstrated by Levi-Montalcini and coworkers.[according to whom?][non-primary source needed] During this period, more insight into the functions of endogenous fatty acid derivatives emerged, and compounds such as oleamide, palmitoylethanolamide, 2-lineoylglycerol and 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.
Primary reports also have provided evidence that PEA downregulates hyperactive mast cells in a dose-dependent manner, and that it alleviates pain elicited in mouse models.[verification needed] PEA and related compounds such as anandamide also seem to have synergistic effects in models of pain and analgesia.
In a variety of animal models, PEA seems to have some promise;[editorializing][citation needed] researchers have been able to demonstrate relevant clinical efficacy in a variety of disorders, from multiple sclerosis to neuropathic pain.
In the mouse forced swimming test, palmitoylethanolamide was comparable to fluoxetine for depression. An Italian study published in 2011 found that PEA reduced the raised intraocular pressure of glaucoma. In a spinal trauma model, PEA reduced the resulting neurological deficit via the reduction of mast cell infiltration and activation. PEA in this model also reduced the activation of microglia and astrocytes. Its activity as an inhibitor of inflammation counteracts reactive astrogliosis induced by beta-amyloid peptide, in a model relevant for neurodegeneration, probably via the PPAR-α mechanism of action.[verification needed] In models of stroke and other CNS trauma, PEA exerted neuroprotective properties.
Chronic pain and neuropathic pain are indications for which there is high unmet need in the clinic. PEA has been tested in a variety of animal models for chronic and neuropathic pain, because cannabinoids, such as THC, have been proven to be effective in neuropathic pain states. The analgesic and antihyperalgesic effects of PEA in two models of acute and persistent pain seemed to be explained at least partly via the de novo neurosteroid synthesis. In chronic granulomatous pain and inflammation model, PEA could prevent nerve formation and sprouting, mechanical allodynia, and PEA inhibited dorsal root ganglia activation, which is a hallmark for winding up in neuropathic pain. The mechanism of action of PEA as an analgesic and anti-inflammatory molecule is probably based on different aspects.[editorializing][citation needed] PEA inhibits the release of both preformed and newly synthesised mast cell mediators, such as histamine and TNF-alpha. PEA, as well as its analogue adelmidrol (di-amide derivative of azelaic acid), can both down-regulate mast cells. PEA reduces the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and prevents IkB-alpha degradation and p65 NF-kappaB nuclear translocation, the latter related to PEA as an endogenous PPAR-alpha agonist. In 2012 it became clear that PEA can also reduce reperfusion injury and the negative impact of shock on various outcome parameters, such as renal dysfunction, ischemic injury and inflammation, most probably via the PPAR-alpha pathway.[editorializing][citation needed] Studies have shown that PEA activates PPAR-alpha and TRPV1 receptors that control inflammation and the sensation of pain. Among the reperfusion and inflammation markers measured PEA could reduce the increase in creatinine, γGT, AST, nuclear translocation of NF-κBp65; kidney MPO activity and MDA levels, nitrotyrosine, PAR and adhesion molecules expression, the infiltration and activation of mast cells and apoptosis.