Halo-Tryptamines

[JDreaming]

There is a family of chemicals that would seem very promising but remains almost totally unknown. Psychedelic drug designers such as Shulgin, Parker and Nichols have made some of their most impressive phenethylamine creations using halogen substitutions. But what about Halo-Tryptamines?

The only halo-tryptamines I know of that have been synthesized are:

5-Fluoro-DMT
5-Fluoro-DET

Which I believe are psychoactive. Ponder a few interesting possibilities, such as:

4-Bromo-N,N-Dimethyltryptamine
5-Chloro-N,N-Dipropyltryptamine
4-Iodo-N-Methyl-N-Isopropyltryptamine
5-Methoxy-Alpha-Bromo-Tryptamine (yikes! Almost too scary to consider.)

Does anyone care to comment on the potential of this family of (hopefully) psychedelic compounds? Might 4 and 5 substituted halo-tryptamines combine some of the interesting traits of the halo-2Cs (2C-B, 2C-C, 2C-I) with psilocin and 5-MeO-DMT-like traits? Would they work? Would they be safe? Which ones would you have the highest hopes for (feel free to build your own!)

And finally: is anyone working on synthesizing these chemicals?

Reputation Comments on this post:

	extremely interesting proposal
	Very impressive idea

[Rush]

SWIM some time ago was interested in those halo derivatives,
in particular 5-Fluoro-AMT that in the tryptamines faq it is said to be "Potent MAOI, an antidepressant rather than a psychedelic." active at 25 mg

oh here i found some other halo ones swim would really like to research:
6-F-AMT, 5-fluorotryptamine,
6-fluorotryptamine and 5- and 6-fluorotryptophans.

[chrisn]

Here's some info in TIHKAL:

I am aware of one of these modifications, specifically on that magical 5-methoxy-position. This is the sterically similar, but metabolically totally dissimilar fluorine analogue, 5-fluoro-alpha-methyltryptamine, or 5-F-a-MT. The fluorine atom is the darling of the manipulators of molecular structure in that it is a form of fake hydrogen. True, as an atomic lump on an aromatic ring it is a lot larger and a lot heavier, but it is a lump that doesn't like to associate with anything else. It's bonding with a ring carbon is the same sort of two-electron bond that the hydrogen atom makes, but it cannot be oxidized off in the same way. So, when a drug has a position of sensitivity to oxidation, and that oxidation is thought to be responsible for some particular pharmacological property, put a fluorine there and you will deny the drug that property. This was discussed in the section on DET where the metabolism attacks a 6-position hydrogen.

And it may play such a role here. When one balances the sort-of stimulant nature of a-MT with the potent psychedelic properties of a,O-DMS, one can ask if the oxidation of the tryptamine system at this 5-position can be of some significance. Tryptamine becomes serotonin by this action. DMT becomes bufotenine by this action. If there is some extension of this to the a-MT world, then the placement of a fluoro group at that position of attack would be interesting. 5-F-a-MT has been made, and it appears to be of reduced activity in man. But it has proven to be an extremely potent monoamineoxidase inhibitor, and strongly influences the brain serotonin levels. The 6-fluoro isomer, 6-F-a-MT, is also effective.

This kind of molecular manipulation is the ultimate treasure of the research pharmacologist. The taking off of one atom and the replacement of it with another. This is the simplest single maneuver that can be done to a drug, and any change in the observed pharmacology must be the result of that change. Some of the explorations have been described in this book are of exactly this nature. Some have been tried. Most have not and are completely unknown. All must eventually be explored if we ever hope to learn what is going on up there in the human mind.

Also:

As a challenge to the hypothesis that hydroxylation at the 6-position of the N,N-dialkyltryptamines might play some role in the expression of the activity, this position was metabolically blocked by the insertion of a fluorine atom there, giving 6-F-DET. This compound, with DET as the control, was studied in some twelve hospitalized alcoholics at doses of about 60, 80 and 100 milligrams intramuscularly. It "does produce autonomic effects, pupillary changes, blood pressure changes; but it does not produce the drifting away into a dream world and other phenomena characteristic for the hallucinogenic activity." The experimenters considered its possible experimental role as an "active placebo" but nothing more was done with it.