AM404

AM404, also known as N-arachidonoylphenolamine,[1][2] is an active metabolite of paracetamol (acetaminophen), responsible for all or part of its analgesic action[3] and anticonvulsant effects.

It is established that AM404 increases concentrations of the endogenous cannabinoid anandamide within the synaptic cleft, contributing to its analgesic activity.

Earlier work on the mechanism of AM404 suggested that the inhibition of fatty acid amide hydrolase (FAAH) by AM404 was responsible for all of its attributed reuptake properties, since intracellular FAAH hydrolysis of anandamide changes the intra/extracellular anandamide equilibrium.

[7] However, this is not the case, as newer research on FAAH knockout mice has found that brain cells internalize anandamide through a selective transport mechanism which is independent of FAAH activity.

AM404 is thought to induce its analgesic action through its activity on the endocannabinoid, COX, and TRPV systems, all of which are present in pain and thermoregulatory pathways.