CYB004 Deuterated Dimethyltryptamine (DMT)

[yoyoman]

I was looking up psychedelic stocks and came across some weird stuff...

I wonder what the structure is? Which hydrogens did they modify? And does that then make it non scheduled but still have identical or close effects?

CYB004 - Cybin

CYB004 CYB004 Deuterated Dimethyltryptamine (DMT) Cybin is developing CYB004 for the treatment of Generalized Anxiety Disorder (GAD) with or without major depressive disorder (MDD). CYB004, a deuterated dimethyltryptamine (DMT), has been shown to exert its psychedelic effects by activating the...

cybin.com

 

[Skorpio]

Deuteration is a nifty trick to delay metabolism while minimally altering pharmacology, as deuteriums act like hydrogens electrostatically, but are harder to remove from a molecule.

This is a good way to make drugs which last longer with very little med-chem optimization (and for the cynics, to easily get new patentable material).

Based on a Google I came up with this:

https://pbs.twimg.com/media/FG11ObAVQAEBknj.jpg

It looks like the carbon alpha to the amine will be fully deuterated and the carbon beta to the amine may be deuterated. They listed some possibility of frustrating the indole carbons, but the main metabolic route of DMT is deamination via MAO-A to indoleacetic acid, and the carbons closest to the amine are likely to have the greatest effect on this reaction.

 

[Skorpio]

Double post to add clarity, it seems only the hydrogens on the alpha carbon (to the amine) are involved in the MAO catalytic cycle. Deuterating this carbon should be sufficient, as the first step in deamination is the removal of an alpha hydrogen.

Maybe they are trying to impair compensatory CYP450 metabolism, or maybe they are trying to broaden the chemical space that is patented. I know what my guess is.

Below is the catalytic mechanism of monoamine oxidase.

 

[yoyoman]

I did some more googling and found the patent, and some other stuff. Looks like they're also making a trimethyl.. like Aeruginascin.

Also found this:

Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines - PubMed

Aeruginascin (4-phosphoryloxy-<i>N</i>,<i>N</i>,<i>N</i>-trimethyltryptammonium) is an analogue of psilocybin (4-phosphoryloxy-<i>N</i>,<i>N</i>-dimethyltryptamine) that has been identified in several species of psilocybin-containing mushrooms. Our team previously reported the synthesis...

pubmed.ncbi.nlm.nih.gov

Looks like some are active, but 4-hydroxy is active and not 4-acetoxy. Weaker too. I've always wondered about it, because i have had a few weird but extra beautiful shroom trips that i was unable to repeat or figure out why they felt so different (better but with unique effects).

https://pubs.acs.org/doi/10.1021/acsomega.0c02208
Looks like 4-HO-TMT is active just weaker at 5ht2a.

These new psychedelic companies are doing some weird stuff, some of it cool, some of it just seems profit oriented.

 

[yoyoman]

I wonder how complex or expensive deuterating is, because it would multiply the known compounds available for experimenting. I wonder how it changes the effect of the DMT.

 

[SpiralusSancti]

As Skorpio said in theory it minimally alters pharmacology, but minimally in case of psychedelics might be just enough to noticeably change effects so who knows.

Multiply the known compounds this way and you might end up with longer acting, stronger, weaker or unexpectedly different psychedelic or non-active substance, there’s still far too little research.

 

[vecktor]

I wonder how complex or expensive deuterating is, because it would multiply the known compounds available for experimenting. I wonder how it changes the effect of the DMT.

depending where you are substituting deuterium it ranges from super easy to incredibly complex or even pointless (replacing indole N-H for example)

with the tryptamines it is dead easy to replace the alpha hydrogens with deuterium simply by replacing LAH with Lithium Aluminum Deuturide in the reduction step
replacing all of the side chain hydrogens is also super easy, synthesis using speeter-anthony via glyoxylamide and again use Lithium Aluminum Deuteride

Deuteration effect on half life and metabolism is generally not very spectacular or worth it pharmacologically. It does theoretically avoid patent infringement (deuteration is something that would be reasonably known to someone practiced in the art so the claim for originality or novelty is very weak) , many companies have gone down this route and almost all of them have failed.

These companies in the psychedelic field care only about the benjamins.

 

[fm3]

depending where you are substituting deuterium it ranges from super easy to incredibly complex or even pointless (replacing indole N-H for example)