ReviewPharmacology research & perspectives2021
Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?
Review in Pharmacology research & perspectives, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Synthesis of 4-Hydroxyphenylamino-Naphthoquinones as Paracetamol-Inspired Analogs: Chemical, In Silico, and Phenotypic Pharmacological Evaluation.Pharmaceutics · 2026Article
- Paracetamol: the potential therapeutic pathways defining its clinical use.Inflammopharmacology · 2025Review
- Paracetamol and Caffeine Combination in Pain Management: A Narrative Review.Pain research & management · 2025Review
- Elderly mice with history of acetaminophen intoxication display worsened cognitive impairment and persistent elevation of astrocyte and microglia burden.Scientific reports · 2024Article
- Contribution of non-steroidal anti-inflammatory drugs to breast cancer treatment:Veterinary world · 2024Review
- Targeting inflammation as cancer therapy.Journal of hematology & oncology · 2024Review
- Drug-Induced Anaphylaxis: National Database Analysis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Chitosan Soft Matter Vesicles Loaded with Acetaminophen as Promising Systems for Modified Drug Release.Molecules (Basel, Switzerland) · 2023Article
- Nonsteroidal anti-inflammatory drug hypersensitivity in a pediatric severe asthmatic population.Pediatric pulmonology · 2023Article
- Analyzing the Antinociceptive Effect of Interleukin-31 in Mice.International journal of molecular sciences · 2023Article
- The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses.Animals : an open access journal from MDPI · 2023Review
- A story of the potential effect of non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease: beneficial or detrimental effects.Inflammopharmacology · 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
- Fructose as a novel nutraceutical for acetaminophen (APAP)-induced hepatotoxicity.Metabolism and target organ damage · 2023Article
- Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment.International journal of molecular sciences · 2022Review
- Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.Frontiers in aging · 2022Review
- Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?Pharmacology research & perspectives · 2021Review
- Fatty acid-mediated signaling as a target for developing type 1 diabetes therapies.Expert opinion on therapeutic targetsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The precise mechanistic action of acetaminophen (ACT; paracetamol) remains debated. ACT's analgesic and antipyretic actions are attributed to cyclooxygenase (COX) inhibition preventing prostaglandin (PG) synthesis. Two COX isoforms (COX1/2) share 60% sequence structure, yet their functions vary. COX variants have been sequenced among various mammalian species including humans. A COX1 splice variant (often termed COX3) is purported by some as the elusive target of ACT's mechanism of action. Yet a physiologically functional COX3 isoform has not been sequenced in humans, refuting these claims. ACT may selectively inhibit COX2, with evidence of a 4.4-fold greater COX2 inhibition than COX1. However, this is markedly lower than other available selective COX2 inhibitors (up to 433-fold) and tempered by proof of potent COX1 inhibition within intact cells when peroxide tone is low. COX isoform inhibition by ACT may depend on subtle in vivo physiological variations specific to ACT. In vivo ACT efficacy is reliant on intact cells and low peroxide tone while the arachidonic acid concentration state can dictate the COX isoform preferred for PG synthesis. ACT is an effective antipyretic (COX2 preference for PG synthesis) and can reduce afebrile core temperature (likely COX1 preference for PG synthesis). Thus, we suggest with specificity to human in vivo physiology that ACT: (i) does not act on a third COX isoform; (ii) is not selective in its COX inhibition; and (iii) inhibition of COX isoforms are determined by subtle and nuanced physiological variations. Robust research designs are required in humans to objectively confirm these hypotheses.
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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.