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The catabolic activity of FAAH on anandamide is counterbalanced by N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), which re-synthesizes anandamide from arachidonic acid and ethanolamine Originally reported as an endogenous cannabinoid reuptake inhibitor, AM404 has various roles in nociceptive and thermoregulatory pathways including potentiating the activity of anandamide through inhibition of FAAH, acting as an agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1), inhibiting enzymatic activity of the two COX isoforms (COX-1 and COX-2), and preventing NF-B activation [27,30]

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