Am404

[Reminisant B]

So its been mentioned a few times - the compound which is the active metabolite of paracetamol/acetaminophen which possibly works via endogenous cannabinoid re-uptake inhibition.

http://en.wikipedia.org/wiki/AM404

Does anyone know or have any predictions on its suitability as an analgesic all by itself, would it be absorbed from the GI?

Possibly even a safer version of paracetamol or paracetamol v2. (? Any opinions, this is pure speculation just to confirm I don't know anything about this chemical other than the obvious)

 

[Reminisant B]

According to one article

Daily treatment with AM404 prevented, time- and dose-dependently, the development of thermal hyperalgesia and mechanical allodynia in neuropathic rats.

Doesn't mention route of admin though, also fundamental safety of the chemical.

 

[LuxEtVeritas]

it would be quite expensive to produce and likely no better than the apparent prodrug paracetamol itself unless perhaps the liver toxicity was substantially lower as that is the main drawback with paracetamol

notably paracetamol shoudl be available in products that have adjunct agents that thwart its hepatotoxic nature and this could be done cheaply and easily....but not like anyone seems to care

likely it is also poorly bioavailable

 

[vecktor]

it would be quite expensive to produce and likely no better than the apparent prodrug paracetamol itself unless perhaps the liver toxicity was substantially lower as that is the main drawback with paracetamol

notably paracetamol shoudl be available in products that have adjunct agents that thwart its hepatotoxic nature and this could be done cheaply and easily....but not like anyone seems to care

likely it is also poorly bioavailable

the safer paracetamol was sold for a short while in the UK and pulled because customers didn't buy it, someone else is still pursuing the idea.

http://www.newscientist.com/article/mg18925330.200-poison-plus-antidote.html

 

[LuxEtVeritas]

they probably did not buy it as most are still quite ignorant of the potential dangers of paracetamol and it was not promoted to any viable degree

so awareness, or lack thereof, was likely the issue wit it not succeeding in the marketplace

i believe there are about 16,000 deaths due to it in the US alone and that is substantial and worth making it mandatory to have such an agent included in ALL products sold with the active

 

[Reminisant B]

I guess the problem arrises with things like co-codamol or any other opiate & paracetamol combinations => paracetamols toxicity is whats "supposed" to stop abuse.

Still my real interest is what effects a cannabinoid receptor re-uptake inhbitor would have at higher doses. Something that is impossible with paracetamol and in fact most likely AM404 not least cause they are also Cox inhibitors amongst other things (and deadly). I guess all the pharm companies are probably already there trying to make something which can be patent in this area.

 

[Reminisant B]

Cannabinoid compounds are so complex

The anandamide transport inhibitor AM404 reduces ethanol self-administration

The mechanism of action of AM404 does not involve cannabinoid CB1 receptors as the CB1-selective antagonist SR141716A did not block the reduction of ethanol self-administration induced by the anandamide uptake blocker. Moreover, 3-(1,1-dimethylheptyl)-(–)-11-hydroxy-delta 8-tetrahydrocannabinol (HU-210), a classical cannabinoid receptor agonist, did not affect ethanol self-administration. The effects of AM404 are not mediated by either vanilloid VR1 receptors or cannabinoid CB2 receptors because it is not antagonized by either the VR1 receptor antagonist capsazepine or the CB2 antagonist AM630. These results indicate that AM404 may be considered as an innovative approach to reduce alcohol consumption.

That was written in 2005 though.