α-methyltryptophan and α-methylserotonin

[MagickalKat777]

Has anyone done any research into these in humans? The only articles that I can find talk about rats and give a general hypothesis that α-methyltryptophan would produce α-methylserotonin in humans and that α-methylserotonin seems to function as an extremely long half-life serotonin. The abstracts that I have found show that α-methyltryptophan is turned into α-methylserotonin and α-methyltryptamine (in much lower quantities) and that α-methyltryptophan actually reduces regular serotonin levels in the brain.

It sounds like α-methyltryptophan could be a promising anti-depressant. α-methylserotonin doesn't appear to cross the BBB but α-methyltryptophan does. What do you all think?

The only thing that concerns me is whether or not αMS would be quite toxic in the human body. α,O-DMS most certainly is and Shulgin said that 4-HO-αMT was similarly toxic.

I also am curious if α-methyltryptophan would act as a prodrug to α-methylserotonin and whether or not that product would have hallucinogenic effects.

Here are some articles that I found:

http://www.researchgate.net/publica...sis_and_degradation_of_serotonin_in_the_brain
http://www.nature.com/jcbfm/journal/v10/n1/abs/jcbfm19901a.html
http://www.sciencedirect.com/science/article/pii/0197018689901058
http://www.sciencedirect.com/science/article/pii/0028390877900065

I found other papers but they speak of synthesis so I can't post them here.

Also there is the excerpt from TiHKAL's αMT entry:

There is some interesting biochemistry and pharmacology all around the edges of α-MT. The 4-hydroxy analogue of α-MT has been looked at in human subjects. It is reported to be markedly visual in its effects, with some subjects reporting dizziness and a depressed feeling. There were, however, several toxic signs at doses of 15 to 20 milligrams orally, including abdominal pain, tachycardia, increased blood pressure and, with several people, headache and diarrhea. The 5-hydroxy analogue of α-MT is also a well-studied compound, but not to my knowledge in man. It can be called α-methylserotonin (α-M-5-HT or α-MS), and it is an effective inhibitor of 5-hydroxytryptophan decarboxylase which is the immediate precursor to serotonin (5-HT). The amino acid tryptophan, without the 5-hydroxy group but with an α-methyl group, is α-methyltryptophan, and it is readily metabolized by the rat to α-MS. In the pineal, it mimics serotonin rather than melatonin, and there is no evidence that it is acetylated on to a melatonin analogue. This α-methyl blocking of the amine group from metabolic deamination represents a half-way step in the modification of serotonin to allow it to enter into the central nervous system, i.e., the protection of the amine group from deamination because of its alpha-methyl substituent. The rest of the needed modification is the methylation of the 5-hydroxy group as well. This yields alpha,O-dimethylserotonin which allows the entry of this serotonin-like product (α,O-DMS) directly into the brain. In all this casual use of the Greek letter alpha to indicate the carbon atom next to the nitrogen atom of the tryptamine side-chain, readers of the very old literature should remember that the letter alpha used to be used to indicate the 2-position of the pyrrole ring.

 

[Hammilton]

I would be really concerned about neurotoxicity. Alpha methyl analogues of monoamines have been known to lesion the brain. Alpha methyl dopamine is very bad, and I believe the same is true for norepinephrine.

Maybe it's fine, I dunno.

 

[MagickalKat777]

Yeah neurotoxicity would be a concern of mine as well. I don't know though. I used an awful lot of α,O-DMS (well over a gram, possibly more) and years later I don't appear to severely impacted by it. My abuse of MDXX was far more damaging than α,O-DMS was. I lost my capacity to do mathematics almost immediately after I started doing MDXX (most of my MDXX was MDA or MDA/MDMA combo until the later years when I got a hold of moon rocks), I gained insomnia, eventually developed panic disorder...

α,O-DMS was definitely more toxic to me in the immediate term (nausea, vomiting, diarrhea, tachycardia, etc) but it doesn't seem to have left lasting damage. My HPPD is from 2C-I and everything else is most likely from MDXX although after almost 3 years of abstinence I am starting to improve. When I started rolling, I stopped doing research chemicals for years and I quickly went downhill just doing pills once a week versus tripping 3 or 4 times a week in the past. That's not to say that I believe I won't ever develop cancer or have limbs fall off or whatever as a result of my usage of research chemicals because that would just be stupid but I digress.

I'm curious if anyone else has thoughts on this. I think one thing that would be concerning to me is how much αMT does α-methyltryptophan create and circulate. I didn't see any data on this in the studies that I saw but once again, I don't have full text access to most of them.

Maybe its better left alone now that I think about it. Chances are that it would probably be a lot like α,O-DMS or 4-HO-αMT in toxicity.

 

[atara]

http://en.wikipedia.org/wiki/Methyldopa

It may inhibit 5-hydroxytryptophan decarboxylase, if methyldopa is any indication. The resulting effects would be antiserotonergic, a far cry from AMT.

As for alpha-methylserotonin, who knows? Bufotenine was already weird.

 

[sekio]

IF alpha-methylserotonin is anything like alpha,O-dimethylserotonin (5-MeO-AMT)... it's probably not worth the investment to make any. 5-MeO-AMT is universally regarded as a rough and tuff, shithouse fighter of psychedelics.

I think one thing that would be concerning to me is how much αMT does α-methyltryptophan create and circulate. I didn't see any data on this in the studies that I saw but once again, I don't have full text access to most of them.

I think more 5HTP is decarboxylated than plain tryptophan in the body by an order of magnitude or two. I wouldn't expect a lot of AMT to be formed.

 

[MagickalKat777]

It is things like this that make me curious about α-methyltryptophan though.

There was a gradual increase of α-methylserotonin and decrease of serotonin so that the concentration of α-methyl-serotonin rose to 6 times that of the naturally occurring amine in 48 hr, falling to 3 times its concentration in 96 hr.

http://www.researchgate.net/publica...sis_and_degradation_of_serotonin_in_the_brain

I'm not necessarily interested in the possible psychedelic applications (although something tells me that α-methylserotonin could potentially act as a psychedelic once α-methyltryptophan has been converted to it) - the half-life is far too long for my tastes - but maybe any applications in regards to depression and such.

I think that it would indeed be far too toxic though to be worthwhile in any way. It does make me curious as to whether or not α,O-DMS has similar effects in regards to natural serotonin levels in the brain. Maybe that could explain why it is so toxic and long-lived? I've had a high dose have a 20+ hour plateau period and had no sleep for days...

 

[nuke]

I posted a big thread here previously containing a lot of valuable pharmacological data relating to the neurotoxicity of these or similar alpha-substituted compounds published I believe in PNAS in the 70s... It would be a shame if that thread had been scrapped at some point by the mods. Interestingly, some of the compounds actually caused monoamine elevation instead of depletion after acute administration.