ArticlePloS one2015
Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Discovery of a long-acting nanocrystal formulation of INND-2201, a new co-drug of pregabalin and palmitoylethanolamide with synergistic analgesic effects.Pharmaceutical science advances · 2025Article
- Palmitoylethanolamide as a Supplement: The Importance of Dose-Dependent Effects for Improving Nervous Tissue Health in an In Vitro Model.International journal of molecular sciences · 2024Article
- Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function.Biomolecules · 2022Review
- Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- The Basal Pharmacology of Palmitoylethanolamide.International journal of molecular sciences · 2020Review
- Toward multifunctional anticancer therapeutics: post-synthetic carbonate functionalisation of asymmetric Au(i) bis-N-heterocyclic carbenes.Chemical communications (Cambridge, England) · 2020Article
- Building and Testing PPARγ Therapeutic ELB00824 with an Improved Therapeutic Window for Neuropathic Pain.Molecules (Basel, Switzerland) · 2020Review
- Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer's Disease.Journal of clinical medicine · 2020Article
- Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease.Frontiers in pharmacology · 2019Review
- Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect.Frontiers in pharmacology · 2018Article
- The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations.British journal of pharmacology · 2017Review
- The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line.Pharmacology research & perspectives · 2017Article
- Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy.British journal of clinical pharmacology · 2016Review
- Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration.Frontiers in aging neuroscience · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palmitoylethanolamide (PEA) has antinflammatory and antinociceptive properties widely exploited in veterinary and human medicine, despite its poor pharmacokinetics. Looking for prodrugs that could progressively release PEA to maintain effective plasma concentrations, we prepared carbonates, esters and carbamates at the hydroxyl group of PEA. Chemical stability (pH 7.4) and stability in rat plasma and liver homogenate were evaluated by in vitro assays. Carbonates and carbamates resulted too labile and too resistant in plasma, respectively. Ester derivatives, prepared by conjugating PEA with various amino acids, allowed to modulate the kinetics of PEA release in plasma and stability in liver homogenate. L-Val-PEA, with suitable PEA release in plasma, and D-Val-PEA, with high resistance to hepatic degradation, were orally administered to rats and plasma levels of prodrugs and PEA were measured at different time points. Both prodrugs showed significant release of PEA, but provided lower plasma concentrations than those obtained with equimolar doses of PEA. Amino-acid esters of PEA are a promising class to develop prodrugs, even if they need further chemical optimization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.