AM404
 | This article is missing information about history of discovery — who gave it this codename?. (December 2022) |
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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.[4] Chemically, it is the amide formed from 4-aminophenol and arachidonic acid.
Pharmacology
It is established that AM404 increases concentrations of the endogenous cannabinoid anandamide within the synaptic cleft, contributing to its analgesic activity.[5] This has been well characterised as involving endocannabinoid transporter inhibition, but the precise transporter responsible is yet to be determined.[5][6][7]
AM404 was originally reported to be an
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.[6]
It is this mechanism which is inhibited by AM404.
AM404 is also a
vanilloid receptors causing vasodilation which is inhibited by the vanilloid receptor antagonist capsazepine.[8]
The anticonvulsant action is mediated through
CB1 receptors.[4]
See also
- VDM-11 (2-methyl analogue)