ArticleProceedings of the National Academy of Sciences of the United States of America2009
Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 2 of them syntheses that pooled it.
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
109 citing papers in PubMed, 2 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence.Frontiers in psychiatry · 2022Pooled it
- Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence.Nutrients · 2021Pooled it
- A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain.Inflammopharmacology · 2022Trial
- Associating Emergency Medical Services personnel's workload, trauma exposure, and health with the cortisol, endocannabinoid, and N-acylethanolamine concentrations in their hair.Scientific reports · 2020Trial
- Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study.Pain research & management · 2020Trial
- Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial.BMC anesthesiology · 2018Trial
- Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Trial
- Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Targeting microglial NAAA-regulated PEA signaling counters inflammatory damage and symptom progression of post-stroke anxiety.Cell communication and signaling : CCS · 2025Article
- Chronic palmitoylethanolamide administrationFrontiers in cellular neuroscience · 2025Article
- The platelet and plasma proteome and targeted lipidome in postpartum dairy cows with elevated systemic inflammation.Scientific reports · 2024Article
- Metabolomic profiles predict clinical severity in patients with obstructive sleep apnea-hypopnea syndrome.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2024Article
- Fluorescence-Based Enzyme Activity Assay: Ascertaining the Activity and Inhibition of Endocannabinoid Hydrolytic Enzymes.International journal of molecular sciences · 2024Review
- NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.Nature communications · 2024Article
- Administration of Linoleoylethanolamide Reduced Weight Gain, Dyslipidemia, and Inflammation Associated with High-Fat-Diet-Induced Obesity.Nutrients · 2023Article
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- BRAF(V600E) mutation together with loss of Trp53 or pTEN drives the origination of hairy cell leukemia from B-lymphocytes.Molecular cancer · 2023Article
- Effects of Long-Term Oral Administration ofBrain sciences · 2023Article
- Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out.Diseases (Basel, Switzerland) · 2023Review
- Reinventing Radiobiology in the Light of FLASH Radiotherapy.Annual review of cancer biology · 2023Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Identifying points of control in inflammation is essential to discovering safe and effective antiinflammatory medicines. Palmitoylethanolamide (PEA) is a naturally occurring lipid amide that, when administered as a drug, inhibits inflammatory responses by engaging peroxisome proliferator-activated receptor-alpha (PPAR-alpha). PEA is preferentially hydrolyzed by the cysteine amidase N-acylethanolamine-hydrolyzing acid amidase (NAAA), which is highly expressed in macrophages. Here we report the discovery of a potent and selective NAAA inhibitor, N-[(3S)-2-oxo-3-oxetanyl]-3-phenylpropanamide [(S)-OOPP], and show that this inhibitor increases PEA levels in activated leukocytes and blunts responses induced by inflammatory stimuli both in vitro and in vivo. These effects are stereoselective, mimicked by exogenous PEA, and abolished by PPAR-alpha deletion. (S)-OOPP also attenuates inflammation and tissue damage and improves recovery of motor function in mice subjected to spinal cord trauma. The results suggest that PEA activation of PPAR-alpha in leukocytes serves as an early stop signal that contrasts the progress of inflammation. The PEA-hydrolyzing amidase NAAA may provide a previously undescribed target for antiinflammatory medicines.
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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.