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7-substituted-tryptamine & B-dragonfly

7 methoxy AMT is also known and I do not believe it to be psychedelic I think it was more a sedative, if I can find the ref I will post it.
7-methoxy DMT has been synthesised by Julia my notes don't say whether it had any activity.

I think 7 methoxy theory does not hold water, look at the directions the lone pairs go in the indole, then look at the dragonfly and hemi fly (methoxy benzofuran) series, the constrained (furan) lone pairs on the active hemi flies point the other way. ie the 2 oxygen lone pairs point towards the side chain. and in the other active isomer the 5 oxygen points away from the side.

This is what Glennon was trying to explore with the isotryptamines where the side chain is relocated to the 4 position, I think these are active agonists though I don't know whether they were found to be hallucinogenic. The isotryptamines have the lone pairs corresponding to the 2 position oxygen pointing toward the side chain. just as in the active hemiflies.
they were only tested in animals and yes they had higher affinity but seemed not to substitute for the DOM training drug
I haven't read the full paper in a long time and I don't seem to have a copy any more, if anyone has,
Glennon J Med Chem. 1980 Nov;23(11):1222-6.
and Glennon et al J Med Chem. 1984 Jan;27(1):41-5.
let me know :)

so if there is an overlay of 7 trypt and 4 phen it isn't as simple as it seems. then again I could be totally wrong, I often am :)

The GUT of psychedelia will come eventually, I think that Nichols current model is going the right direction and once some other GPCR's are structurally elucidated rather than modelled on supposition based on bovine rhodopsin then things will get very interesting.
 
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LuxEtVeritas said:
well if there is ever a GUT of phsychedelica i am real curious to see where salvinorin falls in 8o
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indeed!!
salvianorin not really a psychedelic, it is there to make you feel guilty for killing plants for food. =D
plants have feelings too.
 
Ask Sasha

You could always just call Sasha up and ask him! He is extremely friendly and approachable, and now that his macular degeneration is so severe he can no longer read, I'm sure he would love to get calls from nerds like us with questions about SARs.
 
Salvinorin and psychedelic GUT

LuxEtVeritas said:
well if there is ever a GUT of phsychedelica i am real curious to see where salvinorin falls in 8o
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I personally think it is absurd to seek a GUT of psychedelic pharmacology, as different compounds can have immensely disparate subjective effects. However, if there were such a GUT, Salvinorin-A would not fit into it because it is a selective kappa opioid receptor agonist.

I hope you all don't believe Dave Nichol's rabidly reductionist view that all psychedelic effects are mediated through the 5-HT2A/C receptors because that is complete bollocks. Each drug has a unique pharmacological profile, and many of them are more selective at receptors other than the 5-HT2 subtypes.
 
well if there is ever a GUT of phsychedelica i am real curious to see where salvinorin falls in
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in the corner with N2O, ibotenic acid, dxm, and dramamine, wearing dunce caps
 
Serotonergic receptors in the rat stomach fundus:
7-hydroxy-N,N-dimethyltryptamine. (5 in Table 1) possesses the lowest affinity of any congener examined thus far.
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http://doi.wiley.com/10.1002/qsar.19860050404

Conditioned avoidance response modification, rats:
This experiment established that 5-acetoxy-N:N-dimethyltryptamine (5AcO-DMT: acetyl bufotenine) and 4-methoxy-N:N-dtmethyltryptamine (4MeO-DMT) have a significantly greater effect than 7-methoxy-N,N-dimethyltryptamine (TMeO-DMT) or 6MeO-DMT.
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http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&ID=5678&DocPartID=5454

The neurotoxicity data regarding 5,7-dihydroxytryptamine is enough to make me wanna stay the hell away from them, let alone a thiol substitution that might prove even more inhibitory or toxic. Though, if hugo is correct, perhaps these could spawn very potent compounds like 6-OH-DA analogues, but I don't think I'm going to give them a shot.

7-bromotryptamine is supposed to be pretty potent at some serotonergic receptors, iirc. 5-methoxy-7-bromotrypamines might be a safer place to start testing, as the halogens tend to stay put. Something tells me it's a lot less simple than this though, given that n-substituted phenethylamine psychedelics are for the most part inactive.
 
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^way to use data and facts to support your arguments, jeez, you just ruined a lot of chemdraw masturbating sessions
 
Everytime someone disrupts masturbation over drug chemistry, the devil kills a kitten. =D
 
nuke said:
Serotonergic receptors in the rat stomach fundus:


Conditioned avoidance response modification, rats:
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Two questions:

Q1: what 5-HT receptor was used in the rat fundus study?

Q2: Do you really think that impairment of conditioned response to foot shock in rodents is a reasonable paradigm for assessing the psychedelic properties of a compound?
 
^^I've always wanted to visit Pala. Is that where Bansky is hiding these days? ;)
mad_scientist said:
Now that is interesting. I had just assumed that the 7-substituted tryptamines were inactive, but on a quick flick through TIHKAL it looks like Shulgin tested 6-substituted compounds (which were all inactive) but never made any 7-substituted analogues at all.

The only thing I would be wary about is that 5,7-dihydroxytryptamine is a known compound that is a selective serotonergic neurotoxin, used to preferentially destroy serotonergic neurons for research, in the same way that MPP+ or 6-hydroxydopamine are used to destroy dopaminergic neurons in the study of parkinsons disease.
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Here's a post of mine from an old thread:

From Tihkal:

#40. 5-MEO-MIPT
[7-MeO-MIPT] showed something going on at 20 mg orally with perhaps a little distortion in the visual field. And, separately, at 70 milligrams orally there might have been a light-headedness after a few minutes. Nothing more. It, too, has been given the kiss of death by being declared inactive at the 50 milligram level.

To see if the 7-position corresponds to the 4-position of phens, something like 5-meo-7-ethyl-N,N-DMT would be interesting to test. The example above is pretty meaningless for a two reasons ...

1. The 7-Meo would correspond to TMPEA, which is inactive even as a phenethylamine. Add a halogen or an alkyl or a thioalkyl and you're set.

2. Moving a substituient to the 7-position still won't have the 2,4,5 substitution pattern. Adding a 5-meo would fix this.

Here's another old post by Nuke:

Here's a list of neurotoxic/potentially so tryptamines:
4,5-DiHydroxy-T Very Neurotoxic
5-MeO-DiPT Questionably Neurotoxic
5,6-DiHydroxy-T Very Neurotoxic
5,7-DiHydroxy-T Very Neurotoxic
6,7-DiHydroxy-T Moderately Neurotoxic
4,5-DiOne-T Very Neurotoxic
2-amino-alpha-carboline Neurotoxic
2,n-DiMethyl-Harmine Very Neurotoxic
Harmane/Norharmane Moderately Neurotoxic
2-Methyl-Norharmane Very Neurotoxic
Harmaline - Somewhat Neurotoxic
1-TriClMe-1,2,3,4-tetrahydro-beta-carboline Very Neurotoxic
1-TriBrMe-1,2,3,4-tetrahydro-beta-carboline Very Neurotoxic
Ibogaine - Somewhat Neurotoxic

By neurotoxic I mean negative neuronal functioning (cell death, diminished transporter/transmitter/precursor/enzyme concentrations) somewhere in the brain that is long lasting or permanent.

My worry with 7-substituted things is how the body goes about attacking such compounds in the body, and whether the 5-MeO things might be somewhat dangerous in the first place. Preferentially, neuronal cells seem to 5-hydroxylate raw tryptamines and o-demthylate and 6-hydroxylate 5-MeO-Ts (aside from partial and full n-deamination). But how are the 7-things metabolised? Could they form something inherently dangerous, or be so themselves? We really need someone to administer some new things to mice or rats or chimps and see how their brains cope.
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And from the omniscient ex-bluelighter, Helios:

7-tryps.

--------------------------------------------------------------------------------

Dead End. (>98% pred.)
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http://www.bluelight.ru/vb/showthread.php?p=4619956&highlight=meo*#post4619956
 
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Palanesian said:
Two questions:

Q1: what 5-HT receptor was used in the rat fundus study?

Q2: Do you really think that impairment of conditioned response to foot shock in rodents is a reasonable paradigm for assessing the psychedelic properties of a compound?
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1.) I dunno, I only have the one page. If someone has the rest, help us out.
2.) About as good as anoretic activity in rats shows stimulant activity (not perfect). But there's a good chance that this is showing us its potency (in rats) and that it's going to do something rather than nothing at all (in rats). Whereas QSARs will show us how well a compound will do these things in simulations of a specific enzymatic (which has different mutant forms in some of us) process in computers. The only real way to know if you've discovered the next spiritual penicillin or arsenic is by eating some yourself.
 
Brofaromine

Interesting compound (image below), not a tryptamine but it has the 5-methoxy,7-bromo substitution pattern and a benzofuran where the indole nitrogen would be.

Anyway it's a monoamine oxidase inhibitor.

Like I say it's possibly extrapolating a tad to far to have real implications! but still good to see that potential substitution pattern on a psuedo-indole - knowing it's involved in monoamines.
 

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All points considered,I wager to say that the we have too small (human)pharmacological data with a too narrow set of compounds.Some have the wrong substituents at 5,some have maybe the wrong pattern at the N and most just don't have one at pos. 7.I'm just not giving up too early (and I wouldn't like it when Helios would be right ...).

GUT definitively is no exact science (now you know 8) ) and fractals might look similar but are seldom identical.But the psychedelicists (and synthesists!) like to apply the creative synasthetic blurring to "go west" and who knows where we will land!At new psychedelics?Stimulants?Entactogens?Candyflips in one?

I think the best strategy would be 1) taking the hybrid which works on both,phens and tryps: the alpha-Methyl and 2) make with it the few examples with the kown substitution patterns.A few are already known,Heckyll mentioned them,looking interesting-but knowing the 7-Methoxi would give us clearly more direction!Julia,I think,didn't test the (often very interesting) compounds on humans (officially...).

Just suspecting that the N,N-Dialkyl is wrong here (7-bromo-T activity Another hint per nuke?Dondante raising also a few good points) and advising to remain open and flexible on the 7-xy story.Maybe,we even need a third,yet unknown and slightly different environment around the basic N,maybe its the piperazine which would yield (finally) fruitful compounds ;)

Note:I too think the indole isn't/can't be necessarily a simple methoxi/furan isostere/mimic,I just see that there is some more room to manipulate (2,3-MDA still a simple stimulant!)-possible that a 4,5-diXY is crucial for 5-HT2 activity or,as the other possibility,balanced and/or more potent entactogenic activity is quite easier to be found and finetuning having more playground!I mean AMT could be a good start,no? If you compare amphetamin and AMT? 7-Methoxi-AMT,sedative?So is MMDA,right f&b?

Of course,I could be wrong.More often than Vecktor I am.

Another note:you shouldn't be guided by 5,7-'s neurotoxicity,or else you shouldn't eat 2C-B,TMA-2 and the likes.

Third note: of course you'll get a selectivity issue,often you get (part. with indoles)-but the good drugs are seldom the very selective ones,right?

4th and final note: now who wants to forbid me masturbating (besides the catholic church)?
 
You may be right about the neurotoxicity, at least about the halogens.

...5-hydroxy-. 7-chlorotryptamine (50. pg of free base) did not cause any significant damage. to central catecholamine. or. indoleamine neurons
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The only chlorinated derivative that we have studied,. 5-hydroxy-7-chlorotryptamine,. appeared to be inactive
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http://www.blackwell-synergy.com/doi/abs/10.1111/j.1749-6632.1978.tb31520.x?journalCode=nyas
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1749-6632.1978.tb31531.x

There's the synthesis for 5-methoxy-7-chlorotryptamine-2-carboxylic acid here: http://www.freepatentsonline.com/4614807.html

You should easily be able to go from there to amine substitutions, I think. I wonder if you'd even need to worry about that, because it may not be a substrate for MAO-A with that bulky halogen.
 
Look what I found ... just as I suspected! =D =D =D

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
 
so im confused as to the parallels when 2,4,5 TMA (TMA2) is certainly potent, obviously the halogens are much more, one order of magnitude. Here we are seeing two orders...and this may only have to do with MAO susceptibility via oral dose, dose anyone have the ki for tma-2 vs dob?

go find though^
 
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