Acetaminophen (APAP)

Acetaminophen (also known as paracetamol) is a widely used non-opioid analgesic and antipyretic medication used to treat mild-to-moderate pain and fever (StatPearls, 2023). It is not a biological target itself, but a small molecule drug that interacts with several physiological pathways to exert its therapeutic effects (DrugBank, 2024). Its primary mechanism of action involves the inhibition of cyclooxygenase (COX) enzymes, particularly in the central nervous system, which leads to decreased prostaglandin synthesis (PubMed, 18811451). Additionally, acetaminophen is metabolized into AM404, which modulates the endocannabinoid system and activates TRPV1 receptors, contributing to its analgesic properties (PubChem, 2024). While generally safe at therapeutic doses, it carries a significant risk of severe hepatotoxicity and acute liver failure in cases of overdose due to the production of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) (NIH LiverTox, 2020).

Other names

ParacetamolN-acetyl-p-aminophenolAPAP4-HydroxyacetanilideTylenolPanadol

Acetaminophen inhibits prostaglandin synthesis by reducing the active oxidized form of the cyclooxygenase (COX-1 and COX-2) enzymes, particularly in the brain where peroxide levels are low (StatPearls, 2023). It also undergoes metabolic conversion by fatty acid amide hydrolase (FAAH) to N-arachidonoylphenolamine (AM404), which acts as an indirect endocannabinoid agonist and a TRPV1 receptor agonist (PubMed, 16046116). Additionally, it may stimulate descending serotonergic pathways to inhibit pain transmission in the spinal cord (DrugBank, 2024).