AM-404

AM-404 (N-arachidonoylphenolamine) is an active metabolite of paracetamol (acetaminophen) and a well-characterized research compound that modulates the endocannabinoid system. It acts as an endocannabinoid reuptake inhibitor, preventing the cellular transport and inactivation of anandamide (AEA), thereby indirectly elevating synaptic endocannabinoid levels. Additionally, AM-404 is a potent agonist of the transient receptor potential vanilloid 1 (TRPV1) channel and has been shown to directly inhibit voltage-gated sodium channels (specifically NaV1.7 and NaV1.8) in peripheral nociceptive neurons. It also exhibits weak agonist activity at cannabinoid CB1 and CB2 receptors and weakly inhibits cyclooxygenases (COX-1 and COX-2). Discovered by Alexandros Makriyannis and his team, AM-404 is widely studied as a key mediator of paracetamol's analgesic and antipyretic effects.

Other names

N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamideN-(4-hydroxyphenyl)arachidonamideN-arachidonoylphenolamine