Chetan J. Girase,
Prashant R. Wagh,
Anand G. Gavale,
Sujata S. Girase,
Narendrasing R. Girase,
Ghanshyam M. Chavan,
- Assistant Professor, Department of Pharmacy, SVS’s Dadasaheb Rawal Pharmacy College, Dondaicha, Maharashtra, India
- Assistant Professor, Department of Pharmacy, SVS’s Dadasaheb Rawal Pharmacy College, Dondaicha, Maharashtra, India
- Assistant Professor, Department of Pharmacy, SVS’s Dadasaheb Rawal Pharmacy College, Dondaicha, Maharashtra, India
- Assistant Professor, Department of Pharmacy, SVS’s Dadasaheb Rawal Pharmacy College, Dondaicha, Maharashtra, India
- HOD, SVS’s Dadasaheb Rawal Pharmacy College, Dondaicha, Maharashtra, India
- Principal, SVS’s Dadasaheb Rawal Pharmacy College, Dondaicha, Maharashtra, India
Abstract
In this review, acetaminophen is described as one of the most widely used analgesic and antipyretic medications worldwide due to its effectiveness and reduced gastrointestinal toxicity compared with traditional NSAIDs. Its precise mode of action is still unclear despite widespread therapeutic use. Acetaminophen has little peripheral anti-inflammatory effect and largely acts within the central nervous system, in contrast to NSAIDs, which mainly block peripheral cyclooxygenase (COX) enzymes and lower inflammation. Its pharmacological profile was not adequately explained by early theories that suggested suppression of COX-1, COX-2, and the contentious COX-3 isoform as the main mechanism. According to recent research, acetaminophen acts via several core routes that overlap. The production of the active metabolite AM404 from p-aminophenol in neural tissues is a significant current theory. In order to decrease nociceptive transmission and pain perception, AM404 increases endocannabinoid signaling, activates TRPV1 receptors, and modifies descending serotonergic inhibitory pathways. Despite acetaminophen’s moderate peripheral anti-inflammatory effects, these pathways account for its strong analgesic and antipyretic effects. Therefore, rather than being a straightforward cyclooxygenase inhibitor, acetaminophen is currently understood to be a centrally acting multimodal analgesic.
Keywords: COX, COX-3, AM404, Endocannabinoid, TRPV1, Serotonergic Pathway.
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Research and Reviews: A Journal of Pharmaceutical Science
| Volume | 17 | |
| 02 | ||
| Received | 12/06/2026 | |
| Accepted | 03/08/2026 | |
| Published | 07/08/2026 | |
| Publication Time | 56 Days |