Paracetamol Metabolite (AM404)

Paracetamol, or to give it the US preferred name acetaminophen, has been in use for (guess work) probably a century or so. It has an awkward reputation, whilst it is commonly used for mild-moderate pain relief, and to some extent as an anti-pyretic, it has the unenviable reputation as being hepatotoxic in doses not that much greater than the therapeutic dose.

The way in which paracetamol causes pain relief has not always been clear, but it seems as though recent work has shed some light on it’s mode of action. And quite surprising and interesting it is too.

Paracetamol appears to be metabolised to N-(4-hydroxyphenyl)arachidonoylethanolamide (AM404), and it is this metabolite which is thought to be responsible for it’s pain relieving properties.

This was thought to be an endogenous cannabinoid reuptake inhibitor, but may actually be a substance which prevents the breakdown of endogenous cannabinoids, by virtue of it’s Fatty Acid Amide Hydrolase inhibition, hence boosting the level of endogenous cannabinoids (similar to MAOIs which prevent the breakdown of endogenous sympathomimietric amines – adrenaline/dopamine etc, by monoamineoxidase – MAO)

The similarity between AM404 and Anandamide, can clearly be seen.

Another  interesting fact is that Anadamide is the amide of Arachidonic Acid, which is a polyunsaturated omega-6 fatty acid.

There is much interest in fish oils, and other vegetarian sources of omega-X fatty acids. There is some belief that they help to protect myelin.

There are various seed sources of omega fatty acids, linseed – Flax seed, being popular. Hemp seed also contains various fatty acids, although according to this wiki page on Omega Fatty acids, it isn’t as useful as Flax.

I’m not that keen on flax seed, it tends to make me gag, but I find Hemp seed much more palatable. Peanut oil also seems to contain both arachidonic acid and Arachidic acid, and is sometimes sold as arachis oil.

I’ve no idea where I’m going with this post, it just seems a QI (quite interesting) topic. And in some ways it gives me hope that perhaps further research into Fatty Acid Amide hydrolase Inhibitors, or endocannabinoid reuptake inhibitors, like AM404 the paracetamol metabolite, may result in more effective neuropathic pain relieving medications.


One thought on “Paracetamol Metabolite (AM404)

  1. Walnuts. I came across a research where in Sweden walnuts had been given to a test group and in two weeks their blood vessels had become much more flexible. This was done as research in to prevention of strokes where blood cloths travel in our system and when they get stuck we risk a stroke. By having more flexible blood vessels this can be prevented to a big degree. I started thinking that perhaps this could also help my myelin. So I have since then (a few years now) been having a handful of walnuts daily. Does it work with HNPP? I do not know, but the benefit in preventing strokes makes it worth it in my opinion.

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