ArticleJournal of pain research2017
First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid.
Article in Journal of pain research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 47 citations in OpenAlex.
- Mechanistic Insights into the Analgesic Action of Acetaminophen: Its Bioactive Metabolite Induces Peripheral Analgesia in Addition to Central Analgesia.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Review
- The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring acetaminophen prodrugs and hybrids: a review.RSC advances · 2024Review
- Involvement of cannabinoid receptors in depression of the putative nociceptive response in spinal cord preparations isolated from neonatal rats.The journal of physiological sciences : JPS · 2023Article
- Pain Management in Children Admitted to the Emergency Room: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- An Updated Review on the Metabolite (AM404)-Mediated Central Mechanism of Action of Paracetamol (Acetaminophen): Experimental Evidence and Potential Clinical Impact.Journal of pain research · 2023Review
- Towards Non-Targeted Screening of Lipid Biomarkers for Improved Equine Anti-Doping.Molecules (Basel, Switzerland) · 2022Review
- Identification of CB1 Ligands among Drugs, Phytochemicals and Natural-Like Compounds: Virtual Screening and In Vitro Verification.ACS chemical neuroscience · 2022Article
- Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.Frontiers in aging · 2022Review
- On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.Neurotoxicity research · 2021Review
- Paracetamol (Acetaminophen) and the Developing Brain.International journal of molecular sciences · 2021Review
- Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action.Temperature (Austin, Tex.) · 2021Review
- Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing.Journal of pain research · 2021Review
- Cannabis and Autoimmunity: Possible Mechanisms of Action.ImmunoTargets and therapy · 2021Review
- Article
- Pharmacological Management of Adults with Chronic Non-Cancer Pain in General Practice.Pain and therapy · 2020Article
- A Guide to Targeting the Endocannabinoid System in Drug Design.International journal of molecular sciences · 2020Review
- Repurposing Antibacterial AM404 as a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells.Cancers · 2019Article
- New approaches and challenges to targeting the endocannabinoid system.Nature reviews. Drug discovery · 2018Review
- An insight into paracetamol and its metabolites using molecular docking and molecular dynamics simulation.Journal of molecular modeling · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404). AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic neurons, as well as inhibiting synthesis of PGE
Indexed as
Identifiers
What OpenQuestion holds
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.