Paracetamol works primarily through central analgesic mechanisms involving inhibition of prostaglandin synthesis and activation of descending serotonergic pathways. It acts as a reducing cosubstrate on the peroxidase site of the prostaglandin H2 synthetase enzyme, lessening the availability of radicals needed for prostaglandin production. Unlike traditional NSAIDs, its anti-inflammatory effects are weak due to the presence of peroxide tone during inflammation which reduces its action peripherally. Additionally, paracetamol is metabolized in the brain to an active compound (AM404) that influences cannabinoid receptors and activates TRPV1 receptors, contributing to its analgesic effects.
Mechanism Details
- Paracetamol inhibits cyclooxygenase (COX) enzymes, mainly COX-2 under low peroxide conditions, reducing prostaglandin synthesis, which are mediators of pain and fever.
- It enhances central pain inhibition by activating descending serotonergic pain pathways.
- Metabolite AM404 formed in the brain activates cannabinoid receptors and TRPV1, modulating pain signals.
- The drug lacks significant anti-inflammatory action because high peroxide levels during inflammation counteract its inhibition effect on COX enzymes.
This combination of mechanisms explains paracetamol's effectiveness as an analgesic and antipyretic with minimal anti-inflammatory impact.
