عرض بسيط للتسجيلة

المؤلفEsh, Christopher J.
المؤلفChrismas, Bryna C.R.
المؤلفMauger, Alexis R.
المؤلفTaylor, Lee
تاريخ الإتاحة2024-05-30T07:11:47Z
تاريخ النشر2021-07-18
اسم المنشورPharmacology Research and Perspectives
المعرّفhttp://dx.doi.org/10.1002/prp2.835
الاقتباسEsh, C. J., Chrismas, B. C., Mauger, A. R., & Taylor, L. (2021). Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?. Pharmacology Research & Perspectives, 9(4), e00835.
معرّف المصادر الموحدhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85111827822&origin=inward
معرّف المصادر الموحدhttp://hdl.handle.net/10576/55656
الملخصThe 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.
اللغةen
الناشرWiley-Blackwell
الموضوعacetaminophen
arachidonic acid
cyclooxygenase
mechanism of action
العنوانPharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?
النوعArticle
رقم العدد4
رقم المجلد9
ESSN2052-1707
dc.accessType Open Access


الملفات في هذه التسجيلة

Thumbnail

هذه التسجيلة تظهر في المجموعات التالية

عرض بسيط للتسجيلة