4-thio-DMT aka "Thiopsilocin"

[Hammilton]

I was speaking more of its ability to get inside the protein and provide the correct conformation.

Right, and considering the potency of DMT (with an MAOI), hydrogen bonding probably isn't all that important, that what is more important is the protection from MAO it affords, that 5-MeO-DMT is likely as potent as it is not because of the hydrogen bonding the methoxy group allows, but because it better prevents MAO from destroying it.

AFAICT, hydrogen bonding isn't likely involved in the increased potency. Then again, there's only one way to know.

Does anyone know of differences in potency between RIMAs and irreversible MAO inhibitors?

 

[hugo24]

Does it prevent MAO destroying it BECAUSE of that hydrogen bonding?

 

[Hammilton]

No, they're entirely unrelated.

Just about any substitutent will prevent it from being destroyed. an a-methyl for amphetamine, three methoxy's for mescaline (though judging from potency only, they're apparently not very effective).

Look at the triptans, they're protected from MAO.

 

[fastandbulbous]

Right, and considering the potency of DMT (with an MAOI), hydrogen bonding probably isn't all that important, that what is more important is the protection from MAO it affords, that 5-MeO-DMT is likely as potent as it is not because of the hydrogen bonding the methoxy group allows, but because it better prevents MAO from destroying it.

AFAICT, hydrogen bonding isn't likely involved in the increased potency. Then again, there's only one way to know.

Does anyone know of differences in potency between RIMAs and irreversible MAO inhibitors?

5-methoxy DMT isn't protected from MAO and the methoxy group probably is the important factor in the increase in potency over DMT as it'll form a hydrogen bond with the serine residue of one of the transmembrane subunits (the same region where the oxygen of the carboxamide group of LSD forms a hydrogen bond with).

The 4-thiol substituted DMT had chance to be fairly impervious to MAO anyway as the replacement of the 4-oxygen with a sulphur in PEAs produces some fairly potenent competetive MAOIs - compare 2,4,5-TMPEA, which is inactive orally at silly doses, with 2C-T, which is active at 100mg - the only difference between the two is the replacement of oxygen with a sulphur atom. Any changes at the 4 pos of PEAs seem to produce compounds that prevent MAO changing conformation to the active enzyme, such as the 4 halogen or 4-alkyl substituted derivatives. The 4-thiol DMT will also probably be more lipid soluble although I've no idea how that would impact on the potency of ring substituted tryptamines (as they're a weird bunch, what with internal hydrogen bonding and all manner of molecular weirdness going on).

One thing for certain, it'll stink to high heaven - like to the extent of making AMT seem positively fragrant in comparison

 

[Beenhead]

5-methoxy DMT isn't protected from MAO and the methoxy group probably is the important factor in the increase in potency over DMT as it'll form a hydrogen bond with the serine residue of one of the transmembrane subunits (the same region where the oxygen of the carboxamide group of LSD forms a hydrogen bond with).

exactly


I tend to call enzymes,proteins, and receptors proteins....

And I was speaking more of its ability to bind in the receptor, with the thiol, there is nothing to latch onto on that side of the molecule... right?

 

[UnfortunateSquid]

Is there not an acidity/toxicity issue here?

I'd not ingest anything containing an Aromatic-S(II)-H moiety.

 

[PsychedelicPeptide]

Yeah I bet you would have terrible gas. Or perhaps bad breath. Even worse would be if it makes you sweat and the molecule finds ways to seep out of your skin. Yuck... one thing's for certain, GI issues and psychedelics don't mix well. No one wants to hallucinate on the toilet. =(

 

[hugo24]

Its probably a metal chelator,yes.So you can flush your mercury out which you got from your last fish meal ...

The other thing preventing it from being active in vivo is its oxidation to form the disulfide,it happens quite easily to thiophenols (and cystein as well).Or it gives a chinoid "thion".