4ho-dmt activity

[andruejaysin]

Does anyone know why shrooms are active orally? No other dmt compound seems to be.

 

[fastandbulbous]

Well best reason I can think of is that it's resistant to the action of MAO-A, which does a number on DMT or 5-methoxy DMT, making them inactive orally. As to why it's resistant, rather than just accepting that it is rather open to guesswork, but I think it's likely to have something to do with the possible hydrogen bond between the nitrogen of the side chain and the hydrogen of the 4-hydroxy group. That interaction with the nitrogen atom stops it from being in the right place for the active site of MAO-A, so it doesn't get metabolized.

You'd have to confirm everything above (esp the second bit!), but I don't quite know where at the moment.

As for DET, DPT, DiPT etc. the bigger alkyl groups block the active site of MAO-A, preventing their metabolism. This results in the 5-methoxy being active along with the 4-hydroxy and even the ring unsubstituted parent molecules.

Yeah, I'm pretty certain it'll be all about MAO-A

 

[andruejaysin]

The first part seems self-evident. As for the second, your guess is the best (only) I've heard so far. Thanks.

 

[C6H6]

Would be interesting to know if 4-OH-tryptamine is also active, orally or other. Btw, sumatriptan is another dimethyltryptamine that's orally active.

 

[fastandbulbous]

Yeah, but it has an extra carbon atom between the sulphur atom and the indole nucleus, allowing it to 'bend' further round and interact with the nitrogen of the sidechain. Well that or the whole N-methylsulphonamide group is large enough to prevent the MAO-A active site from getting anywhere near the sidechain nitrogen. hydroxy/methoxy groups are tiny compared with an N-methylsulphonamide group

 

[BilZ0r]

Thanks for that we snippet of medicinal chemistry C6H6, interesting.

 

[C6H6]

A quick search of the good old Merck Index brought up 3 more DMT-derived, orally active triptans:

 

[yaesutom]

Interesting, has anyone here ever tried any of those?

I've always been curious about a possible orally active DMT, maybe without psychedelic effects but retain some of DMT's "nootropic" or brain-speeding up effects.

 

[andruejaysin]

I wish I was smart enough to understand C6H6's post, I'm at least honest enough to admit I don't. But you gave me a starting point to research it, which is half the fun.