The Big & Dandy Psychedelics of the Future Thread

Psychedelics_r_best

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Shulgin obviously didnt include a great deal of the possible tryptamines out there in TiHKAL, while he pretty much covered a load of PEA's in PiHKAL.

I would like to dedicate this thread to possibilites of tryptamines that we would like to see created, have an inclination might be satisfying, or whatnot. If anyone has some imaginative phenethylamines, though, thats great too, but personally phenethylamines just arent my thing.

What about iso-propyl substitutions such as 4-iP-MiPT? What even about methyl or ethyl substitutions? Is there any reason they might not be as active as the commonly known methoxy and hydroxy group substitutions? What if you have a 5- substituted hydroxy compound? I want more possibilities!

Also, I have an inclination that 4,5-MDO-MiPT might be a good one.
 

MattPsy

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N-benzyl's

In particular, a N-(4-bromo-2-methoxy)benzyl

And 4 & 5 methoxy subsituted Tryp's, but with the methoxy groups tethered in a furan arrangement like the dragonfly PEA's.
 

MattPsy

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Psychedelics_r_best said:
What about iso-propyl substitutions such as 4-iP-MiPT? What even about methyl or ethyl substitutions? Is there any reason they might not be as active as the commonly known methoxy and hydroxy group substitutions? What if you have a 5- substituted hydroxy compound? I want more possibilities!

Also, I have an inclination that 4,5-MDO-MiPT might be a good one.
Non polar ring substitutions are likely to be very weak or inactive. Ideally, you want something nice and electronegative, but without it being polar; this is why hydroxy groups are bad on rings usually, as they hinder it getting through the BBB. 4-HO-DMT (Psilocin) is an odd one because the OH hydrogen gets attracted to the ethylamine sidechain's nitrogens lone pair, which sort of wraps around.
 

MattPsy

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Why 6 fluoro?
From what I can see, 7 would be better as then it better matches the structure of the dragonfly PEA's; the indolic nitrogen replacing one of the furan oxygens.
Oh, and, makes it trifluoromethyl instead of just fluoro for more affinity :) .
 

Jamshyd

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For the third year in a row:

PiPT (N-propyl,N-isopropyltryptamine). This one actually IS mentioned in TiHKAL - But only mentioned as a name in a list. Is it *that* impossible to synth?? geez.

*cries*
 

yoyoman

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i'd love to see 4-AcO / HO-NMT.. got a 'gut' feeling about that one, sorta like 4-aco-dmt
 

MattPsy

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EN21 said:
Several fluorinated analogues were made and the results were not very spectacular. (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed The 5-MeO-N-(4-bromobenzyl)-T is also without activity. (google for dissertation jensen tryptamine)

Any idea about N-(2-methoxy)benzyl ? I couldn't find the article you mentioned.

The 4-brominated benzyl idea was kinda just musings of my own about rough dimeric forms *shrug*.
 

EN21

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Here is the PhD thesis, i mentioned: deposit.ddb.de/cgi-bin/dokserv?idn=973960833&dok_var=d1&dok_ext=pdf&filename=973960833.pdf
It refers to an article from Glennon which claims enormous activity for this one.
1: J Med Chem. 1994 Jun 24;37(13):1929-35. Links
Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines.

* Glennon RA,
* Dukat M,
* el-Bermawy M,
* Law H,
* De los Angeles J,
* Teitler M,
* King A,
* Herrick-Davis K.

Department of Medicinal Chemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540.

The effect of 15 different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of compounds (i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobenzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with > 100-fold selectivity. Although parallel structural modification in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.
Additionally I know of some unsuccessful bioassays.
What a pity
 

IGNVS

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i say we get multiple MeO groups in 4,5,6 or 4,5,7 positions...

im also intrested if are any tryptamines with anything on the beta position are active
 

egor

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3,4,5-TRIMETHOXY-beta,beta-DIDEUTEROPHENETHYLAMINE seems as if it may be a good too for introspective work from some of the accounts in pihkal, and it sounds as if it has at least moderate visuals also.

3,5-DIMETHOXY-4-ALLYLOXYPHENETHYLAMINE seems to have much promise.

2c-e-fly would be my best bet for a truly fulfilling 2c-fly analog.

and this one may be on the oldies list, but good ol' 4-ho-dpt.
 

Psychedelics_r_best

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Well, what has anyone to say on 4-iP-MiPT or 5-iP-MiPT. My knowledge in chemistry is not so extensive so as to predict the possible physiological or psychological effects. Anyone have any input?
 

MattPsy

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Since this is now RC's in general, not just Tryps...

For going for pure super-rediculously-potent stakes, I suggest the following :) :




Psychedelics_r_best said:
Well, what has anyone to say on 4-iP-MiPT or 5-iP-MiPT. My knowledge in chemistry is not so extensive so as to predict the possible physiological or psychological effects. Anyone have any input?
For the reasons I mentioned earlier, very likely inactive. An isopropyl is not a good ring substiuent, from what I understand.
 

fastandbulbous

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Psychedelics_r_best said:
Well, what has anyone to say on 4-iP-MiPT or 5-iP-MiPT. My knowledge in chemistry is not so extensive so as to predict the possible physiological or psychological effects. Anyone have any input?
They need the oxygen atom to be present as it's the oxygen of the 5-OH group of serotonin that binds to the equivalent site on the receptor protein chain. Without the oxygen you've just got a bulky alkyl group that can't form a hydrogen bond and would likely severely reduce any affinity for the receptor


The effect of 15 different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of compounds (i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobenzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with > 100-fold selectivity. Although parallel structural modification in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.
Does it give any indication as to whether these compounds are agonists, mixed agonists-antagonists or pure antagonists though, as having a high affinity will count for bog all if they turn out to be antagonists
 

Psychedelics_r_best

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Ah, I see. So what if perhaps, you have a substitution with a carbon bound to the ring, in turn bound to three oxygen atoms, or a carbon bound to the ring and double bound to an oxygen and single bound to a methyl group? or what about 5-AcO substitutions?
 

MattPsy

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Acetoxy is just a ester - esters are derived from hydroxys.

The ester is stripped off in the body (hydrolyzed) to leave the hydroxy group. This is why 4-AcO-DMT feels the same as 4-HO-DMT (Psilocin).

About the substitutions you mentioned:
5-AcO-DMT would likely be similar Ibogaine; ie. pretty unpleasant.
If you want ring substitutions, it seems you need something electronegative and with lone pairs. O & N are really the only ones like this. It is therefore unsurprising that PEA's with 2,5 oxygen substituents and tryptamines with their indolic nitrogen and perhaps oxygen ring substituent are active. F&B can go into more detail...

Interesting thing to note:
S22 7-Br-DMT 170 +/- 17 nM Ki
Quasi-atomistic Receptor Surrogates for the 5-HT2A Receptor:
A 3D-QSAR Study on Hallucinogenic Substances.
Seems -7 halogen substitutions may be active. Funny that, that's where the PEA halogen ones are, heh :) .
 
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