ArticleProceedings of the National Academy of Sciences of the United States of America2025
The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Could NAPQI Contribute to Paracetamol Analgesia? Redox Modulation of Kv7 Ion Channels.Pharmacology research & perspectives · 2026Review
- The psychoactive cannabinoid THC inhibits peripheral nociceptors by targeting NaNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Article
- Acetaminophen's Role in Autism and ADHD: A Mitochondrial Perspective.International journal of molecular sciences · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
Paracetamol has been used for decades to relieve mild-to-moderate pain. Its analgesic effect is mainly attributed to its metabolite, AM404, acting on cannabinoid receptors or TRPV1 channels in central nervous system (CNS) neurons. Here, we show that AM404 is produced by primary sensory neurons. It inhibits sodium current in nociceptor neurons, blocking action potential (AP) generation and reducing nocifensive behavior in naïve and inflamed rats. We demonstrated that this analgesic effect of AM404 is mediated by its direct inhibition of nociceptive voltage-gated sodium channels (Na
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