Mechanisms of paracetamol’s analgesic activity
Sapronova A.D., Poddubny E.A., Eliseeva E.V., Feoktistova Yu.V.
Paracetamol is one of the most frequently prescribed analgesics for the relief of acute and chronic pain, but its mechanism of action remains unclear. It was previously believed that paracetamol, like other nonsteroidal anti-inflammatory drugs, exerts its analgesic activity by inhibiting COX-1 and COX-2 enzymes. However, it was later discovered that the antinociceptive effect is exerted not so much by paracetamol itself, but by its metabolite N-acylphenolamine (AM404), which affects vanilloid and endocannabinoid receptors. There is also evidence that other systems and receptors in the human body are involved in the analgesic activity of paracetamol. The authors decided to analyze and systematize the available data on this topic to better understand the analgesic mechanism of action of paracetamol and apply this knowledge in the treatment of acute and chronic pain in patients.
For citations: Sapronova A.D., Poddubny E.A., Eliseeva E.V., Feoktistova Yu.V. Mechanisms of paracetamol’s analgesic activity. Pharmateca. 2026;33(1):73-80. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.1.73-80
Authors’ contribution: E.A. Poddubny – study concept and design. A.D. Sapronova – data collection and processing, writing. E.V. Eliseeva, Yu.V. Feoktistova – editing.
Funding. This study was funded by the authors.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.
Keywords
paracetamol
analgesia
analgesic mechanism
N-acylphenolamine
About the Authors
A.D. Sapronova, Department of General and Clinical Pharmacology, Pacific State Medical University, Vladivostok, Russia; ORCID: https://orcid.org/0009-0007-9551-9575E.A. Poddubny, Cand. Sci. (Med.), Associate Professor, Department of General and Clinical Pharmacology, Pacific State Medical University, Vladivostok, Russia; poddubnyy.ea@tgmu.ru, ORCID: https://orcid.org/0000-0003-0075-303X, eLibrary SPIN 6109-7743 (corresponding author)
E.V. Eliseeva, Department of General and Clinical Pharmacology, Pacific State Medical University, Vladivostok, Russia; ORCID: https://orcid.org/0000-0001-6126-1253
Yu.V. Feoktistova, Department of General and Clinical Pharmacology, Pacific State Medical University; Regional Children’s Clinical Hospital No. 1, Vladivostok, Russia; ORCID: https://orcid.org/0000-0003-4070-9842
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