7-substituted-tryptamine & B-dragonfly

[kidamnesiac]

Here are the last words in that article:

The binding af®nity of this compound towards the
5-HT2A receptor is predicted to be Kiˆ3.2 nM, close to the
experimental binding af®nity of LSD (Kiˆ2.5 nM). Some of
these compounds have been synthesized in the meantime,
allowing for a critical evaluation of our model.

Meaning they made it, and it proved to be shit. QSAR sucks.

Their strongest hit is DOI with a Diethylamidopropyl group stuck to the N. So imagine 3 carbons, the third having the amide group, and two ethyl groups off the amide N, stuck onto the DOI primary N.

Once again, this is freaking cake to make, if it was hot shit it would be all over.

 

[Dondante]

^^True. QSAR is far from perfect, but did they actually make that compound, ko3? I see no evidence that have done so ... although they probably did and didn't publish due to disappointing results. Anybody want to check with Nichols on this?

This compound has been discussed here before:

http://www.bluelight.ru/vb/archive/index.php/t-215318.html

Either way, 7-Br-DMT is still promising! QSAR has it's shortcomings, but the activity of 7-Br-DMT gives weight to the overlay argument. The details just need to be worked out ...

Also, I found this on N,N-dimethylmescaline ...

Drug-induced discrimination: A description of the paradigm and a review of its specific application to the study of hallucinogenic agents. 1983. Richard A. Glennon, John A. Rosecrans, Richard Young.

http://www3.interscience.wiley.com/cgi-bin/abstract/113309751/ABSTRACT?CRETRY=1&SRETRY=0

"N-Methylation of several phenalkylamines
results in at least a two- to threefold decrease in potency in
the discrimination studies; thus, it would be anticipated that the
N-methyl derivatives of mescaline would not be active in man until doses
of at least 900-1500 mg have been administered. Unfortunately, Nmethylmescaline
was only evaluated to 25 mg; N,N-dimethylmescaline
was inactive at 550 mg, although, interestingly, some activity was
observed at 800 mg."

As others have mentioned, it's not surprising that N-alkylated phens have weaker affinity, seeing as DMT has weaker affinity than 5-HT.

And here's a link to the abstract for the other paper:

http://www3.interscience.wiley.com/cgi-bin/abstract/68502121/ABSTRACT

 

[hugo24]

N-Dealkylation could be an issue for activity in vivo here.

Why do you think N-substitution seems to help with tryptamines but kills activity in phens? I guess its needed with simple trypts to stop metabolism, or maybe more likely to make it less polar so it can get into the brain?

But with AMT, addition of a methyl group to the nitrogen reduces activity, according to tihkal, i assume alpha,N,N-TMT is even less potent. What about nor-LSD?

Thats why we philosophers say you'll never understand everything or that the closer you get to the higher truths, the more fuzzy it appears (hello GUTH...).Like when trying to split a quark,at the very moment you applied a successfull amount of force-you'll see you just produced Another quark!Damned!

raises both hands,voice and head The teachings of the elementary,synthesis by elementarism and the cycle is again fullfilled,all is whole,eternal,just IS-and the mystery shall remain intact! awaits amen from the public

If that is not enough for you,try a good dose of Epiphanol

 

[Ham-milton]

Epiphanol? sweet

 

[Reminisant B]

Thats why we philosophers say you'll never understand everything or that the closer you get to the higher truths, the more fuzzy it appears (hello GUTH...).Like when trying to split a quark,at the very moment you applied a successfull amount of force-you'll see you just produced Another quark!Damned!

That's exactly the beauty of it. Try as hard as you can to figure out the grand unified theory of PEA/Tryps and just as your making a correlation a NEW one appears (potentially messing up the logic) but one that could be very fun! [or useful scientifically]

 

[fastandbulbous]

the isomers of a-MT follow a similar pattern to MDMA....ie opposite of the PEAs.....(+)-a-MT is the more potent isomer....however, if you compare the structures of (+)-a-MT with d-LSD, (-)-DOM, etc....they overlays perfectly...hydrogens oriented the same way.....further confirming (in my mind) that there is a great overlay between the structure/activity relationship between PEAs and indolethylamines. Is what I am saying making sense? I lack the chemistry vernacular to properly articulate my thoughts.

Bit more discussion of the absolute stereochemistry of 5HT hallucinogens in this thread


PS - Nice colourful pics MGS, makes up for my having to do away with mine because of gallery restrictions on numbers

 

[Morninggloryseed]

You should really consider issuing your dragonfly write up in a PDF (compete with pics). It is a slow day here, so I'm glad to draw some up if you need them to be. Its a wonderful read.

 

[haribo1]

God I'm so hip it's painful sometimes

Yes, when we met & couldn't see your face over your pelvis 8)

 

[izo]

You should really consider issuing your dragonfly write up in a PDF (compete with pics). It is a slow day here, so I'm glad to draw some up if you need them to be. Its a wonderful read.

+1
its a really good introduction for those who lack in understanding scientific papers like nichols hallucinogens summary.

 

[(zonk)]

I know it seems like it's been established that 7sub-tryps are a "dead end". But I didn't see anything mentioned about 4-HO-7-sub-tryps like 4-ho-7mt, 4-ho-1,7-dmt and maybe the 5-methoxy counterparts to those 2. Perhaps subs at he N-position ruin hallucinogenic activity in the way that they do with alpha-methyl sub-tryps. A 4-ho would enhance hallucinogenic effects of any tryptamine no?

 

[planckunit]

I know it seems like it's been established that 7sub-tryps are a "dead end". But I didn't see anything mentioned about 4-HO-7-sub-tryps like 4-ho-7mt, 4-ho-1,7-dmt and maybe the 5-methoxy counterparts to those 2. Perhaps subs at he N-position ruin hallucinogenic activity in the way that they do with alpha-methyl sub-tryps. A 4-ho would enhance hallucinogenic effects of any tryptamine no?

What? What makes you think they are a dead end? If you know of any reports, please post them. Glennon's articles make me think that stuff like 5-MeO,7Br-DMT or 7-Br-DMT should be more potent than DMT.

 

[(zonk)]

personally. I dont. I would think these 7sub-Ts have the most potential of the tryptamine series, maybe even better than acid! But that is just based on a quick blurb I've read. But the general consensus of this thread says that they think these are not going to be much of anything other than an antidepressant? Their are no trip reports of anykind unfortunatly. I may try experimenting with this but 7MT is SOOOO expensive. They dont seem like very easy compounds to make unfortunatly.

 

[immad]

Look what I found ... just as I suspected!

Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens. Lyon RA, Titeler M, Seggel MR, Glennon RA. Eur J Pharmacol. 1988 Jan 19;145(3):291-7.

Twenty-one indolealkylamines, some of which are known to be psychoactive in man, were examined for their binding interactions with rat brain cortical 5-HT2 receptors labeled with the antagonist radioligand [3H]ketanserin in order to develop structure-activity relationships for binding at these sites. Features investigated included aromatic, alpha-methyl and terminal amine substituents. 4-Methoxy and 5-methoxy substitution impart a higher affinity than 6- or 7-methoxy substitution; a 7-hydroxyl group essentially abolishes affinity whereas a 7-methyl or 7-bromo group enhances affinity. alpha-Methylation has little effect on affinity and, in the one case examined, the S(+) isomer of alpha-methyltryptamine was essentially equipotent with its racemate and twice as potent as its R(-) enantiomer. Terminal amine methylation results in a small but progressive decrease in affinity in the order: primary amine greater than dimethylamine greater than diethylamine. Similarities were noted between these structural requirements for binding and those of the phenalkylamines. Selected compounds (5-methoxytryptamine, N,N-dimethyltryptamine, 5-methoxy-N,N-diethyltryptamine and 5-methoxy-N,N-dimethyltryptamine) were further examined by two-site analysis of displacement studies for [3H]ketanserin specific binding. Hill coefficients were significantly less than unity and computer-assisted analysis indicated that a two-site model better fit the data than a one-site model. In displacement studies using the putative agonist radioligand [3H]DOB to label 5-HT2 receptors affinities were 10-100-fold higher than those using [3H]ketanserin. These results are also consistent with earlier findings using psychoactive phenalkylamines in competition studies for radiolabelled 5-HT2 receptors.

PMID: 3350047 [PubMed - indexed for MEDLINE]

DMT,7-Br
5-HT2A Ki (nM): 170.0

DMT, 7-MeO
5-HT2A Ki (nM): 5,400.0

DMT, 7-OH
5-HT2A Ki (nM): >10,000.0

DMT, 5-MeO,7-Me
5-HT2A Ki (nM): 360.00
Hot ligand: 3H-KETANSERIN

Do you know by chance anything about the 5-HT1a affinity of these compounds?

5-MeO-DMT is very psychedelic, but not that much of a 5-HT2a agonist. Instead, it's very much a powerful 5-HT1a agonist (see Psychedelics and the Human Receptorome).

It'ld be very interesting to find a new psychedelic that's mainly a 1a agonist.

http://download.yousendit.com/B0F70C9E73474325

Sorry, couldnt see how to attach it, am i being a dumbass?

edit: just had a quick look and noticed it says in table 2, if i understand it right, that racemic AMT is a more potent agonist than either enantiomer? Which is the more active enantiomer anyway, i thought it was in tihkal but it seems not. Thought Shulgin would have jumped on that like with DOB/DOM and MDMA in pihkal.

Also the 1-TMT looks potent, anyone know anything about it?

That link seems dead