ArticleProstaglandins & other lipid mediators2008
Acetaminophen: antipyretic or hypothermic in mice? In either case, PGHS-1b (COX-3) is irrelevant.
Article in Prostaglandins & other lipid mediators, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 62 citations in OpenAlex.
- Acetaminophen (Paracetamol) Induces Hypothermia During Acute Cold Stress.Clinical drug investigation · 2017Trial
- Paracetamol: the potential therapeutic pathways defining its clinical use.Inflammopharmacology · 2025Review
- Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Phytochemical mediated modulation of COX-3 and NFκB for the management and treatment of arthritis.Scientific reports · 2023Article
- Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.Journal of veterinary internal medicine · 2023Article
- Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?Pharmacology research & perspectives · 2021Review
- The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans.Scientific reports · 2021Article
- Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action.Temperature (Austin, Tex.) · 2021Review
- Comparison of effects of high and low dose paracetamol treatment and toxicity on brain and liver in rats.Northern clinics of Istanbul · 2020Article
- The investigation of possible roles of central 5-HTInflammopharmacology · 2019Article
- Mammalian cold TRP channels: impact on thermoregulation and energy homeostasis.Pflugers Archiv : European journal of physiology · 2018Review
- Hypothermic activity of acetaminophen; involvement of GABAA receptor, theoretical and experimental studies.Iranian journal of basic medical sciences · 2016Article
- Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans.Frontiers in pharmacology · 2016Article
- TRPA1 mediates the hypothermic action of acetaminophen.Scientific reports · 2015Article
- Survey and critical appraisal of pharmacological agents with potential thermo-modulatory properties in the context of artificially induced hypometabolism.Journal of clinical and translational research · 2015Review
- The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings.Inflammopharmacology · 2013Review
- Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action.Pharmaceutical biology · 2011Article
- Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Review
- Pharmacology.Handbook of clinical neurology · 2010Article
- Uncertain risks of drug related harms, the precautionary principle and limitations of meta-analysis.British journal of clinical pharmacology · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Acetaminophen (AC) reduces the core temperatures (T(c)) of febrile and non-febrile mice alike. Evidence has been adduced that the selectively AC-sensitive PGHS isoform, PGHS-1b (COX-3), mediates these effects. PGHS-1b, however, has no catalytic potency in mice. To resolve this contradiction, AC was injected intravenously (i.v.) into conscious PGHS-1 gene-sufficient (wild-type (WT)) and -deficient (PGHS-1(-/-)) mice 60 min before or after pyrogen-free saline (PFS) or E. coli LPS (10 microg/kg) i.v. T(c) was monitored continuously; brain and plasma PGE(2) levels were determined hourly. AC at <160 mg/kg did not affect T(c) when given before PFS or LPS; at 160 mg/kg, it caused a approximately 2.5 degrees C T(c) fall in 60 min. LPS given after AC (all doses) induced a approximately 1 degrees C fever, not different from that in AC-untreated mice. But this rise was insufficient to overcome the hypothermia of the 160 mg/kg-treated mice; their T(c) culminated 1 degrees C below baseline. LPS given before AC similarly elevated T(c) approximately 1 degrees C. This rise was reduced to baseline in 30 min by 80 mg AC/kg; T(c) rebounded to its febrile level over the next 30 min. At 160 mg/kg, AC reduced T(c) to 4 degrees C below baseline in 60 min, where it remained until the end of the experiment. WT and PGHS-1(-/-) mice responded similarly to all the treatments. The basal brain and plasma PGE(2) levels of PFS mice and the elevated plasma levels of LPS mice were unchanged by AC at 160 mg/kg; but the latter's brain levels were reduced at 1h, then recovered. Thus, AC could exert an anti-PGHS-2 effect when this enzyme is upregulated in the brain of febrile mice. The hypothermia it induces in non-febrile mice, therefore, is due to another mechanism. PGHS-1b is not involved in either case.
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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.