From the Guidelines
Paracetamol's mechanism of action is primarily through the inhibition of prostaglandin production within the central nervous system and peripheral tissues, as demonstrated by recent studies 1. The exact mechanism of paracetamol's analgesic action remains largely unknown, but it is believed to involve the inhibition of cyclooxygenase (COX) enzymes, particularly in the central nervous system.
- Key aspects of paracetamol's mechanism include:
- Inhibition of prostaglandin production, which contributes to its analgesic and antipyretic effects
- Minimal effect on peripheral COX enzymes, resulting in limited anti-inflammatory action
- Influence on the endocannabinoid system and serotonergic pathways, which may also contribute to its pain-relieving effects
- The drug's ability to cross the blood-brain barrier effectively allows it to reach its central site of action, where it can inhibit prostaglandin production and exert its analgesic effects, as noted in the context of its use for various painful conditions 1.
- It is essential to consider the potential risks associated with paracetamol use, including hepatotoxicity, particularly when taken in excessive amounts, as highlighted by studies examining its safety profile 1.
From the Research
Mechanism of Action of Paracetamol
The mechanism of action of paracetamol (acetaminophen) is complex and not fully understood. Several theories have been proposed, including:
- Inhibition of cyclooxygenase (COX) enzymes in the central nervous system (CNS) 2, 3
- Activation of the descending inhibitory serotonergic pathway 2
- Potentiation of the endocannabinoid system through the formation of N-arachidonoylphenolamine (AM404) 4
- Inhibition of prostaglandin synthesis in the brain 5
- Activation of transient receptor potential vanilloid-1 (TRPV1) receptors 4
Key Findings
- Paracetamol has been shown to inhibit COX-1 and COX-2 enzymes, although the exact mechanism of this inhibition is not fully understood 2, 3
- The formation of AM404, a metabolite of paracetamol, has been proposed to activate the endocannabinoid system and contribute to the analgesic effects of paracetamol 4
- Paracetamol has been shown to reduce the levels of prostaglandin E2 in the brain, which may contribute to its antipyretic effects 5
- The antipyretic effect of paracetamol has been shown to occur independently of TRPA1-mediated hypothermia 5
Theories and Proposals
- One theory proposes that paracetamol works as a pro-drug, with the active metabolite being a cannabinoid 4
- Another proposal suggests that paracetamol may have a "redox" mechanism of action, although this is not fully understood 3
- The exact mechanism of paracetamol's analgesic and antipyretic effects is still a topic of debate and research 2, 6, 3, 5