I am very interested in 4,5-MDO-DMT (4,5-methylenedioxy-N,N-dimethyltryptamine) but can find almost no information regaurding this compound, aside from a small entry in TIHKAL and a wikipedia page nothing exists.

Because the 4 and 5 position are the sweet spots to add substitutions to on the DMT molecule, I'm guessing this molecule would be pharmocologically interesting to investigate.

Ive looked at 4-hydroxy-5-methoxy-N,N-dimethyltryptamine, which is reported to be an active psychedelic in humans, the two oxygen atoms at 4 and 5 would be in the same location as they would be with 4,5-MDO-DMT. Now I know this isn't evidence for human activity,but it shows that the molecule would be producing a similar shape in the alpha-helical protiens of the 5HT2a receptor. I was skeptical about a methylenedioxy substituted tryptamine, but in TIHKAL I also found this:

4,5-methylendioxy-N,N-diisopropyltryptamine (4,5-MDO-DIPT) DOSAGE : > 25 mgs

DURATION : unknown

QUALITATIVE COMMENTS : (25 mg, orally) Nothing much happened for about 3 hours, and then I suddenly shot up. I was at the plateau for a fair time, the recovery was difficult to define chronologically. This was in daylight; I was reminded very much of LSD.

So there is at least one active 4,5-MDO-tryptamine out there, though very little information exists on 4,5-MDO-DIPT as well.

Any information regaurding these novel substituted tryptamines would be much appreciated.

I don't know anything about the 4,5 substitution, but I would be interested in 5,6-methylenedioxy-N,N-DMT -- it bears a superficial similarity with 5,6-methylenedioxy-2-aminodindane (MDAI), which I have been extremely interested in for a long time. The methylenedioxy moiety seems to be usually associated with monoamine release (esp. 5-HT), so we might be able to expect 4,5-MDO-DMT (and the 5,6 analog) to have more entactogenic and stimulatory effects.

MDAI was designed by Nichols et al to be a selective 5-HT releasing agent, and the Erowid reports are sparse, but intriguing.

MDAI structure.
https://en.wikipedia.org/wiki/File:MDAI.svg

5-6-MDO-N,N-DMT structure
https://en.wikipedia.org/wiki/File:5,6-MDO-DMT.png

The aminoindane core of the MDAI compound looks different from the indole group from MDO, but the presence of the amine groups makes me think there should be at least *some* interesting in vivo activity.

In the next couple of weeks I'm going to be learning how to use AutoDock modeling software, I'll get back to this as soon as I can.

Blessings
~ND

Thank-you for your thoughts and interest!

Ive been asking around about these novel substituted tryptamines for some time now and gotten absolutley nowhere, of coarse these things are a simple Curiosity to me at this point, but I may invest some real time and effort into their study if I can find sufficient reasoning to do so.

Keep me posted! And thanks again.

I may be wrong on this, but don't substitutions to the 6 position kill the activity of tryptamines?
I was also interested in 5,6-MDO-DMT but as far as what I can glean from shulgins writings it was inactive at 5 mgs when smoked, no further tests were conducted as far as I know, maybe it would be orally active at larger doses, but as far as I know nobody has taken the time to test this.

Here's some of shulgins of thoughts (taken from TIHKAL in 5,6-MDO-DIPT extentions and commentary section)

EXTENSIONS AND COMMENTARY : So why enter an entry into a listing of active compound when it is simply not known if it is active or not? The truth is, that none of these three 5,6-methylenedioxy N,N-disubstituted tryptamines (this one, or 5,6-MDO-DMT or 5,6-MDO-MIPT) has been explored up to an active level, but they are appealing targets in that they have the progression of nitrogen substituents that has proven so valuable in similar sequences of compounds. This is the pattern dimethyl, methylisopropyl and diisopropyl. With both the unsubstituted, and the 5-methoxy-substituted groups, the activity goes from quite potent but requiring parenteral administration, to highly potent and orally active, and back to quite potent and orally active, as the methyl groups are progressively replaced with isopropyl groups. It would be instructive to see if this arrangement was maintained with this methylenedioxy trilogy.

The three closed ring group of substituents mentioned in the pyr-T recipe have also been described with this 5,6-methylenedioxy ring substitution. These could be named 5,6-MDO-pyr-T (the pyrrolidine analogue, mp 110-112 °C), 5,6- MDO-pip-T (the piperidine analogue, mp 150-152 °C) and 5,6-MDO-mor-T (the morpholine analogue, mp 117-119 °C). To my knowledge, none of these has ever been put into man.

(I have also had interest in 2-AI (2-amino-indane) and 5,6-methylenedioxy-2-aminoindane (5,6-MDAI) ive thought that maybe with some clever methoxy substitutions and bromine atom or methyl group some beautiful homologues of DOB, or DOM could be made, but this is all wild speculation, and I have not taken the time to look at these compounds in any depth yet, but who knows, maybe it could work)

I think the jury is still out on that one. There was some evidence that 5,6-dibromo-N,N-DMT (which occurs naturally in some sponges) had antidepressant activity.

http://pubs.acs.org/doi/abs/10.1021/np070371u

SAR tests using tryptaimine and dimethyltryptmaine found that substitutions of hydroxy and methoxy groups were less effective in the 6 position than the 4 or 5 positions, but some activity in dorsal raphe neurons was shown.

http://www.jneurosci.org/content/1/10/1148.short

Blessings
~ND

Thank you for the links!

I really appreciate it.

Ill keep posting any information regaurding novel substituted tryptamines here.

Speaking of novel substitutions to tryptamine compounds, a german mycologist and chemist named Jochen Gartz devoloped a process in which you inoculate the growing substrate of stropharia cubensis mycellium with a novel tryptamine, like, say, N-methyl-N-ethyl-tryptamine (MET) and the stropharia cubensis mycellium will "pick-up" the novel tryptamine from the growing substrate and add a hydroxyl group to its 4 position, so the MET would be "transformed" enzamatically by the mycellium into 4-hydroxy-N-methyl-n-ethyl-tryptamine (4-HO-MET), which would then be present in the fruiting bodies from which it could be extracted. Now, some compounds like 4-hydroxy-5-methoxy-N,N-Dimethyltryptamine are a hassle to produce in the lab, the process is complicated and contains something like 12 steps, but if Gartz was correct this compound could be produced just as easily as fruiting some stropharia cubensis cataphores. Now, think of all the novel compounds that this mycellium could 4 hydroxylate! So many new and novel compounds could be produced!....this is the theory anyway, and while gartz holds the patent on this process, ive never seen any evidence that this process actually works, and ive never heard of any successfully reproducing Gartz experiments, I still feel its a novel idea and its fun to dream about all the new and novel compounds that could be produced.

Please continue to post any good information on novel substituted tryptamines.

That idea was bouncing around the 'Biosynthesis of Novel Tryptamines' thread, over in Advanced Chemistry.

https://www.dmt-nexus.me...aspx?g=posts&t=21776

There was some question over how selective the fungal tryptamine phosphorylase was. It never really went anywhere, since it would be really hard to test to see if you actually got interesting compounds or not.

The other idea we had was to inoculate the substrate with a tryptamine phosphorylase inhibitor (TPI), which *might* make the mushroom biosynthasize psilocin or N,N-DMT instead of psilocybin, but, again, we ran into theoretic problems, since mammalian TPases are usually different from fungal TPases and no one knew any good fungal TPIs.

Blessings
~ND

Go science!

Thank you again!

All the information you have directed me to has been most helpful with my studies, though I wish I could find an example of someone reproducing gartz experiments with successful results.

You brought up 2-aminoindane before, I was thinking if it were possible to add a methoxy group position 4 and a methoxy group to position 7, and then a methyl group or bromine atom to position 5, I feel some homologues of DOM or DOB could be made, but again I have not looked into 2-AI in any depth.

Thank you again!

When you were speaking of the brominated dimethyltryptamines derived from sea sponges it reminded of shulgin mentioning this in the "DMT is everywhere" chapter of TIHKAL, I believe he said they were researching these sponges due to some anti-microbial properties and ended up discovering these brominated dimethyltryptamines and I guess they found a process (by mistake) for converting the brominated DMTs into DMT itself, which is interesting science, its been a while since I read over that section in TIHKAL so sorry if my descriptions of what shulgin said are lacking in detail.

Thank you again, I appreciate all the information you have directed me towards, please keep posting any more information you feel relates to this topic.

While reading TIHKAL this morning I found this paragraph in the DMT extentions and commentary section, much of what shulgin discusses here relates to the topics that have been discussed on this thread, he mentions some compounds that he feels should be active, does anyone know if anybody has taken the time to see if shulgin was correct? Anyway its a small paragraph but there's some good information included in it:

Several simple substitution derivatives of DMT are known. Those that are known to be psychedelic have their own recipes, of course, but the others will be summarized here. The 1-methyl homologue of DMT (1,N,N-trimethyltryptamine) can be prepared from DMT in KOH and DMSO, with CH3I. It forms a picrate salt which melts at 175-179 °C, and bioxalate, mp 174-176 °C. It is more toxic than DMT in rats, but has an identical serotonin binding capacity. The compound with a methoxy group substituent at the 1-position is called Lespedamine, 1-MeO-DMT. With an NO bond, this should be classified as a substituted hydroxylamine. I would love to know if anyone anywhere has ever tried smoking it. I suspect it might very well be active, but it is, to my knowledge, untried. I wonder why it deserves a trivial name, vis., Lespedamine? Two additional ring-substituted derivatives of DMT come from the marine world. 5-Bromo-DMT and 5,6-dibromo-DMT are found in the sponges Smenospongia auria and S. echina resp. I have no idea if they are active by smoking (the 5-Br-DMT just might be) but they are quantitatively reduced to DMT by stirring under hydrogen in methanol, in the presence of palladium on charcoal. A very closely related sponge, Polyfibrospongia maynardii,contains the very closely related 5,6-dibromotryptamine and the corresponding monomethyl NMT. I had the fantasy of trying to scotch the rumor I'm about to start, that all the hippies of the San Francisco Bay Area were heading to the Caribbean with packets of Zig-Zag papers, to hit the sponge trade with a psychedelic fervor. This is not true. I refuse to take credit for this myth. (-A.Shulgin ;TIHKAL)

I believe lespedamine gets a specific name because it was first isolated from the Lespedeza bicolor plant, where it was of interest to plant pharmacologists. I'm not sure when this was, but I imagine the people naming it were interested in it for it's own properties and not just as a novel analogue of DMT.

Found anything on MDO-substiuted tryptamines? This came up in conversation the other day with a friend and reminded me of the question. My friend suggested that there might be some steric hindrance, although we weren't' sure (what's the largest active substitution one can stick on the indole ring?)

Blessings
~ND