Endocannabinoid system modulator (via AM404 metabolite formation)

AM404 (N-arachidonoylphenolamine) is an active central nervous system metabolite of paracetamol (acetaminophen), formed within the brain primarily through FAAH-mediated conjugation. It modulates the endocannabinoid system by weakly activating cannabinoid receptors CB1 and CB2, potently activating the TRPV1 channel, inhibiting cellular uptake of endocannabinoids such as anandamide, and weakly inhibiting cyclooxygenases and sodium channels. These combined actions contribute to analgesic, antipyretic, anti-inflammatory, and neuroprotective effects. Because AM404 itself is not a single molecular target but a pleiotropic modulator acting on several targets, "Endocannabinoid system modulation via AM404 metabolite formation" is not a canonical drug target but rather a mechanism-of-action descriptor for the pharmacology of paracetamol and related ligands[1][2][4][7][9].

Other names

AM404 modulation of endocannabinoid systemParacetamol metabolite AM404 activityN-arachidonoylphenolamine actionEndocannabinoid reuptake inhibitor (context-dependent)

Weak agonism of cannabinoid CB1 and CB2 receptors; Potent activation of TRPV1 (transient receptor potential vanilloid type 1); Inhibition of endocannabinoid transporter, increasing anandamide (AEA) levels; Weak inhibition of cyclooxygenase (COX) enzymes; Inhibition of voltage-gated sodium channels NaV1.8 and NaV1.7