ArticleBritish journal of pharmacology2020
Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis 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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Effects of Analgesics on Self-Reported Physical Function and Walking Ability in People With Hip or Knee Osteoarthritis: A Systematic Review and Meta-Analysis.Physical therapy · 2024Pooled it
- Pharmacological therapy of neonatal analgosedation: current status, dilemmas, and perspectives.Frontiers in pediatrics · 2026Review
- Computational Insights into the Structural Basis for Reduced Hepatotoxicity of Novel Nonopioid Analgesics.ChemMedChem · 2025Article
- Identification and experimental validation of biomarkers associated with the endocannabinoid system in major depressive disorder.Hereditas · 2025Article
- Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.Scientific reports · 2024Article
- 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
- Efficacy of oral mefenamic acidTherapeutic advances in vaccines and immunotherapy · 2023Article
- 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
- Analgesic Action of Acetaminophen via Kv7 Channels.International journal of molecular sciences · 2022Article
- Maternal use of acetaminophen during pregnancy and neurobehavioral problems in offspring at 3 years: A prospective cohort study.PloS one · 2022Article
- Paracetamol (Acetaminophen) and the Developing Brain.International journal of molecular sciences · 2021Review
- Inhibitory effect of intrathecally administered AM404, an endocannabinoid reuptake inhibitor, on neuropathic pain in a rat chronic constriction injury model.Pharmacological reports : PR · 2021Article
- Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action.Temperature (Austin, Tex.) · 2021Review
- A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis.European journal of medicinal chemistry · 2020Article
- Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.British journal of pharmacology · 2020Article
- A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
background and purposeWe previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide) to activate CB EXPERIMENTAL APPROACH: The effects of paracetamol on brain function in Sprague-Dawley rats were determined by functional MRI. Levels of neurotransmitters in the periaqueductal grey (PAG) were measured using in vivo KEY
resultsParacetamol decreased the connectivity of major brain structures involved in pain processing (insula, somatosensory cortex, amygdala, hypothalamus, and the PAG). This effect was particularly prominent in the PAG, where paracetamol, after conversion to AM404, (a) modulated neuronal activity and functional connectivity, (b) promoted GABA and glutamate release, and (c) activated a TRPV1 channel-mGlu CONCLUSIONS AND IMPLICATIONS: The elucidation of the mechanism of action of paracetamol as an analgesic paves the way for pharmacological innovations to improve the pharmacopoeia of analgesic agents.
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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.