5-Alkoxy-tryptamines...

[Limpet Chicken]

I am greatly curious, what with the powerful effect of most of the 5-methoxylated substituted tryptamines at even small doses, the differing alkyl groups, chalcogen groups, and even halogens in some cases, have been manipulated ad nauseam.

Why has nobody decided to change the alkoxy groups present, say for instance, substituting ethoxy, isopropoxy or MAYBE butoxy groups, onto the archetype 5-MeO-tryptamines, so as to create the likes of 5-EtO-DMT, and the other analogues which would follow?

If this would lead to active compounds, I remain perplexed as to why this hasn't been accomplished, as it would lead to a great number of new tryptamines reaady for evaluation.

 

[Jaw Clenching]

5-nonyloxy-tryptamine is a known 5-HT1D agonist.

 

[ChuangTzu]

5-MeSulfonamide-DMT is a known 5HT1 agonist too. It's used to treat cluster headaches. Not a 5-alkoxy DMT but it shows that extensive research has been done in this area. I would assume there are more out there.

I asked Shulgin (on that Ask Dr. Shulgin webpage) about this a while back but he never answered. It seems that up to a certain point (DMT->5-Me-DMT->5-MeO-DMT) bigger substituents increase the potency with respect to the 5HT2 receptors but as you get even bigger (somewhere before 5-MeSulfonamide and 5-nonyloxy) potency goes down to 0. It's too bad the analogue act has put such a huge damper on explorations like this : (

 

[Limpet Chicken]

To hell with the analogue act, fuck it with a large, and rather pointy stick.

 

[Black]

It seems that up to a certain point (DMT->5-Me-DMT->5-MeO-DMT) bigger substituents increase the potency with respect to the 5HT2 receptors but as you get even bigger (somewhere before 5-MeSulfonamide and 5-nonyloxy) potency goes down to 0.

I would guess that that hydro-/lipophily of the substituent would also have an effect on the action of the compound. It seems like hydrophobic or moderately hydrophobic groups are best for increasing potency. hydrophilic groups most likely aren't as good (see 5-HO-DMT aka Bufotenine). that would also rule out your 5-MeSulfonamide-DMT as that is rather hydrophilic.

maybe a moderately lipophilic substituent with roughly the size of the 5-MeSulfonamide would be active as a psychedelic...

 

[fastandbulbous]

You really need to have some sort of atom with lone pairs to increase binding to the 5HT2a receptor - a more likely reason for 5-methoxy DMT being more active than 5-methyl DMT

 

[Riemann Zeta]

What about a 5-amino-DxT or 5-halo-DxT compound?

 

[Smyth]

I seem to recall that 5-fluoro DMT was highly active as an inhibitor. However, the fact that this area of research has died out indicates that there is nothing of any great interest to be salvaged here. I may be wrong, but the idea of such a compound has me retching.

On the other side, sulphur is an interesting element to play with. Particularly important are the 'flat-liner' pills in '97 that contained p-thiomethylamphetamine. SWIM tried some of these and was unable to distinguish the effects from MDMA at the time (although admittedly this was 8 years ago now so his memory may have faded).

 

[Smyth]

Actually maybe it was wrong to bad mouth 5-fluoro-DMT as this does in fact look like a promising compound.

Basically fluorine has properties that mean it is expected to behave like molecular hydrogen or less commonly oxygen [m-fluoro-tramadol is completely useless, and 4-fluoro-PCP and 4-fluoro-fentanyl are substantially weakened - so this theory does have marked limitations].

The hypothesis was that if the 5-postion on the indole nucleus is a site of metabolic deactivation by monamine oxidase enzymes, insertion of the fluorine will help block this giving a much more robust compound than its parent structure. This hypothesis does seem to work and is a central theme in pharmacology having been applied to an endless list of medically important compounds such as sugars etc.

 

[C6H6]

5-F-aMT is supposedly very active and a confirmed 5-HT2A agonist. 5-MeS-tryptamines are also active, which of course is not surprising.

 

[Riemann Zeta]

5-Fluoro-AMT meaning 5-fluoro-alphamethyltryptamine? I don't think that this particular compound would be all that different from AMT. I have nothing against AMT (I have never tried it, so I can't really speak of its effects), but a number of people seem to dislike it. Generally, people seem to like (+)-AET quite a bit more, as it has less of a pressor effect. Thus, it might be interesting to investigate 5-fluoro-AET. Also, I am not sure about the 5- position on indoles being a target for monoamine oxidase. I always assumed that the nitrogen was the primary locus of attack, considering that DMT and 5-MeO-DMT are inactive orally due to MAO activity, but DiPT and 5-MeO-DiPT ("Foxy Methoxy") are.

On an unrelated note, I always thought "flatliner" was PTA, meaning para-thiol-amphetamine, the sulfur analogue of PMA, a truly dangerous pressor agent. PMEA (para-methoxy-N-ethylamphetamine), however, seems to have tremendous untapped potential. Hence, I wonder what PTEA (para-thiol-N-ethylamphetamine) would like? Since substitution at the 4-position on amphetamine seems to ablate central stimulant activity (and direct the compound more toward the 5-HT transporter than the catecholamine transporters), I have always wondered what the para-halo-N-ethylamphetamines would be like. Fluorine is perhaps the only halogen that I think would be safely attempted, as the larger 4-halo-substituted primary amphetamines serve as potent 5-HTergic neurotoxins.

 

[Smyth]

Yes I am not sure WHY the fluorine increases activity. Maybe because it is so electronegative (fluorine is quite an extreme element) and that is just the effects that it elicits. I am guessing that 4-fluoro-effexor is a compound that could be looked at. There is not anything on this in the chemical literature although I do have a list of effexor analogues.

But I think 4-F-AMT is the compound I am looking for. I personally have not tried AMT mainly because RC's are expensive than anything else. I have heard it is quite nasty though which is a bit of a turn-off for me.

Also 4-MTA is what was containde in the flatliner xtc pills.