1 Department of Pharmacology and Therapeutics, Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University Awka, Nnewi Campus, Anambra State, Nigeria.
2 College of Nursing Science Obohia Ndoki, Abia State, Nigeria.
3 School of Nursing Umuahia, Abia State, Nigeria.
Review Article
World Journal of Advanced Research and Reviews, 2022, 16(01), 580-589
Article DOI: 10.30574/wjarr.2022.16.1.1046
Received on 11 September 2022, revised on 13 October 2022, accepted on 16 October 2022
Paracetamol is used worldwide for its analgesic and antipyretic actions. Its spectrum of activity similar to that of NSAIDs and resembles particularly the COX-2 selective inhibitors,but with a lesser anti-inflammatory effect, its metabolism is complex, and its analgesic mechanisms have not been completely understood. It was previously explained to produce analgesia by inhibiting the enzyme cyclooxygenase (COX) which is incorrect, however recent findings revealed that acetaminophen is metabolized to p-aminophenol, which crosses the blood-brain barrier and get metabolized by fatty acid amide hydrolase (FAAH) to yield N-acylphenolamine (AM404). AM404 acts on a number of receptors viz; the transient receptor potential vanilloid-1 (TRPV1) and cannabinoid 1 (CB1) receptors in the midbrain and medulla which are mediators of pain modulation. Moreover it has also been reported to act via Cav3.2 calcium channel. Evidence also show that acetaminophen analgesic action of acetaminophen could be due to its interaction with endogenous neurotransmitter systems, opioid, serotonergic systems and nitric oxide system. additionally, it is also been unraveled that paracetamol may exert novel mechanisms of action, likely relevant for their analgesic action, by modulating protein kinase C epsilon (PKCε) and substance P (SP) in the peripheral sensory neurons. This review is geared towards explaining and updating with experimental proof the analgesic novel mechanism of action of Acetaminophen since it has no ant-inflammory effect
N-acylphenolamine (AM404); PKCε; Acetaminophen; Analgesia; Cyclooxygenase
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Eric Omo Irinmwinuwa, Prince Chiazor Unekwe, Emmanuel Ugochukwu Egba, Emmanuel Chigemezu Metu and Njoku Charles Cherech. Acetaminophen: Ancient drug with a novel analgesic mechanism of action. World Journal of Advanced Research and Reviews, 2022, 16(1), 580-589. Article DOI: https://doi.org/10.30574/wjarr.2022.16.1.1046