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AM404 - bioavaliability and potential modification?

anxiolytic anxiety pain social interaction

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#1 Mind_Paralysis

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Posted 03 September 2016 - 10:11 PM


About a year ago I made a thread regarding some of the newer data on ACETAMINOPHEN/paracetamol - and how it appears to work by inhibiting activity in the Anterior Cingulate Cortex: the part of your brain which sorts between physical and emotional pain, and then sends them on to the correct parts of the brain.

Inhibiting this part of the brain has also been suggested as a form of treatment for Borderline Personality Disorder - I see the logic, but I also challenge it - the hyperemotionality doesn't stem from ACC-dysfunction, it stems from PFC and Amygdal dysfunction.

Moving on - these effects of Paracetamol are mirrored in THC, which seems to inhibit activity in the ACC as well - hence the pain-relieving effects of Cannabis.

In Paracetamol though, this effect is somewhat slower, smoother and subtler, both when it hits, and when it stops. The reason for this is because Paracetamol is actually a PRO-drug for another, EXOgenous compound: AM404 - an SCRI - Selective Cannabinoid Reuptake Inhibitor!!

 

 

References

------------------

The role of the Anterior Cingulate Cortex

http://www.sutherlan...n_ACC_Apr09.pdf

 

THC as a pain-reliever working on the ACC

http://www.smithsoni...9786068/?no-ist

 

 

The wondrous properties of Acetaminophen, as an anxiolytic, antidepressant, and nootropic

 

"Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress"
http://www.jneuroinf.../content/6/1/10


"Acetaminophen Reduces Social Pain - Behavioral and Neural Evidence"
http://pss.sagepub.c...ontent/21/7/931

"The Common Pain of Surrealism and Death Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats"
http://pss.sagepub.c...956797612464786

"Paracetamol potentiates the antidepressant-like and anticompulsive-like effects of fluoxetine."
http://www.ncbi.nlm....pubmed/25340977

 

 

Now, all of these awesome effects... are probably bound to AM404 - one of two active metabolites.

The question now is... can AM404 be synthesized? And how would the bioavailability be? Is it orally active? Can it cross the Blood-Brain-Barrier?

 

These are all important questions... and I cannot find a single answer to any of them, in any source of knowledge that I try to decipher. No matter what, as far as I can see, it should be SUPREMELY EASY to synthesize - just make Acetaminophen and then expose it to the known organic enzymes which create AM404! In fact, someone was kind enough to provide us with a patent to infringe upon...

 

http://pdfaiw.uspto....=DN/20150183737

 

 

With a bit of luck... we might just have one helluva' drug on our hands here, people!

 

 

https://en.wikipedia...404#section=Top
 

 

1070px-AM404_skel.svg.png


Edited by Stinkorninjor, 03 September 2016 - 10:40 PM.

  • Informative x 1

#2 jack black

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Posted 05 September 2016 - 10:40 PM

OK, subscribing to the topic, LOL.

 

BTW:

Price and Availability

Qty

10 mg / $89 Available 50 mg / $369 Available

 

Biological Activity

Competitive and selective inhibitor of carrier-mediated anandamide transport (IC50 = 1 μM). Does not activate CB1 receptors or inhibit anandamide hydrolysis but has been shown to activate native and cloned vanilloid receptors (pEC50 = 7.4). Active in vivo. Also available in water soluble emulsion (Cat. No. 1685).

 

From:

https://www.tocris.c...php?ItemId=2199

 

Edit:

some places have it even cheaper: https://www.caymanch...m/product/90060

 

or rock bottom cheap: http://chemmedshop.c...404-powder-100g

 

However, not sure if it's safe to buy from the last one considering this:

All orders are shipped discretely under the company name "MMS" in a plain white bubble mailer. All charges with show up on your credit card bill as: "Medical Marijuana Store"  All orders are shipped through UPS, DHL, Royal Mail  and  a tracking number will be provided to you.

 

They also have all kinds of controlled substances in stock. Is this a some kind of sting operation?


Edited by jack black, 05 September 2016 - 11:38 PM.


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#3 Mind_Paralysis

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Posted 05 September 2016 - 11:02 PM

Yo! Jack! = ) Cheers for linkage there! There is some problems with these sites though - they require you to be a legit research-company or University or other research-organ, or they won't sell to you.

 

(that can be arranged though... no sweat there - one just has to be prepared to go the extra mile. It might even be possible to organize a group buy and then have someone like Ceretropic do the actual distribution to the buyers! Anything's possible, especially with a chemical which is so well-known and well-spread as Acetaminophen.)

 

Cayman Chemicals has a nice price, but they seem to insist on only offering it in an Ethanol solution... -_-

 

As we both know, that just isn't up to snuff for a trial - ethanol would mess everything up! It's kind of crazy how common that is - dissolving a psychoactive chemical in ANOTHER VERY, *VERY* psychoactive chemical...! Alcohol hits more receptors than I have fingers and toes, it's literally useless as an active solvent when trying out the effects of chemicals.







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