AM404 was originally reported to be an endogenous cannabinoid reuptake inhibitor, preventing the transport of anandamide and other related compounds back from the synaptic cleft, much in the same way that common SSRI antidepressants prevent the reuptake of serotonin. Recent work on the mechanism of AM404 has suggested that the inhibition of fatty acid amide hydrolase (FAAH) by AM404 is likely responsible for all of its attributed "reuptake" properties, since intracellular FAAH hydrolysis of anandamide changes the intra/extracellular anandamide equilibrium.
AM404 is also TRPV1 agonist, and also prevents cyclooxygenase COX-1 and COX-2 and prostaglandin synthesis. AM404 is thought to induce its analgesic action through its activity on the cannabinoid, COX and TRPV systems, all of which are present in pain and thermoregulatory pathways.
↑Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A (2006). [Expression error: Missing operand for > "The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors"]. Eur. J. Pharmacol.531 (1-3): 280–1. doi:10.1016/j.ejphar.2005.12.015. PMID16438952.
↑Glaser, S. T.; Abumrad, N. A.; Fatade, F.; Kaczocha, M.; Studholme, K. M.; Deutsch, D. G. (2003). [Expression error: Missing operand for > "Evidence against the presence of an anandamide transporter"]. Proceedings of the National Academy of Sciences100: 4269. doi:10.1073/pnas.0730816100. edit
↑Högestätt, E. D., B. A. G. Jönsson, A. Ermund, D. A. Andersson, H. Björk, J. P. Alexander, B. F. Cravatt, A. I. Basbaum, P. M. Zygmunt (September 9, 2005). [Expression error: Missing operand for > "Conversion of Acetaminophen to the Bioactive N-Acylphenolamine AM404 via Fatty Acid Amide Hydrolase-dependent Arachidonic Acid Conjugation in the Nervous System"]. Journal of Biological Chemistry280 (36): 31405–31412. doi:10.1074/jbc.M501489200. PMID15987694.
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