Has anyone ever tried to remove the 1,2,4-Triazole group from Rizatriptan? Is it possible to even do so? This is all just out of curiosity of coarse.

-EG

Triazole can act as a leaving group on some substrates, it probably would be a decent leaving group on carbons 2 and 3, but I don't know about position 5. If you could get it to leave, you would still be left with a methyl on the 5 carbon and good luck getting rid of that!

I think Mindlusion's right -- cleaving the N-C bond shouldn't be too hard, but the CH3-C bond isn't going anywhere any time soon.

Also, you've got two tertiary amines in Rizatriptan, so I would worry that anything that messed with the triazole group might also attack the dimethylated nitrogen on the tail.

Blessings
~ND

Thank you the responses, it would have been interesting if it were possible, it could have been a completley unique pathway to active alkylated tryptamine compounds, yeah but I suppose your right about that CH3-C bond.

Thanks

-EG

Thanks ND I never even would have thought about the dimethylated nitrogen being affected, thank you again for the replys, so is this the case with all the triptans? Is there always something there to prevent you from reducing a "triptan" into DMT?

-EG

Well, the nitrogen on the tail end is a tertiary amine. Its not going to react with anything that is going to force the triazole to leave. All you are doing is making the nitrogen on the triazole take back its electrons, not reacting anything with it directly.

Again, I don't know how easily you could remove it where it is located, probably not easily at all. If it was on the indole directly, you could do a nucleophillic aromatic substitution.

It is pretty difficult to work backwards from a single molecule, retro-synthesis is an important technique to solve problems in organic synthesis, but it involves working backwards from the final product, in this case DMT. Its difficult to work backwards from a reactant like you are trying to do here.

Thank you for all the responses, fascinating stuff, like I said before these triptans just are a curiousity to me and I'm not doing serious study involving them ,but rizatriptan, almotriptan, sumatriptan, all looked as though it may be possible to reduce them to DMT, with out doing any in depth research I posted here and got amazing response! I really appreciate the interest as well as all the information I get back! I often over look really obvious problems with my ideas and I'm constantly making neophyte mistakes, so anything that can be said on the subject is very much appreciated. Unfortunately ive been busy on other matters but as soon as I get the free time I'm going to go over these triptans again, though there may not be sufficient reason to do so, interesting stuff reguardless!


-EG

If it were possible to remove the triazole group, leaving just a methyl group in the 5- position, it wouldn't, apparently, be a problem: 5-Me DMT

Very interesting, I'm for sure going to look into 5-Me-DMT.

I've been looking into these DMT homologues recently:

•alpha,alpha,beta,beta-tetradeutero-N,N-dimethyltryptamine ( D4DMT )
(This compound is said to produce an experience that is more intense and for a longer duration that proteo-DMT. "It was observed that the presence of deuterium in the alpha- and beta-positions of the ethylamine side-chain led to a potentiation of the level of DMT in brain" )

•5-Bromo-N,N-Dimethyltryptamine (5-br-DMT)
(5-Bromo-DMT and 5,6-dibromo-DMT are found in the sponges Smenospongia auria and S. echina resp. I have no idea if they are active by smoking (the 5-Br-DMT just might be)-Alexander shulgin TIHKAL. Aside from shulgins speculation that 5-Br-DMT May be active when smoked I've found that this compounds Wikipedia page states "Anecdotal reports published by Hamilton Morris indicate that 5-Bromo-DMT freebase is psychoactive in humans when smoked at doses between 20 and 50 milligrams" all and all I would say that this compound looks very promising)

•1-methoxy-N,N-dimethyltryptamine (lespedamine; 1-MEO-DMT)
( The compound with a methoxy group substituent at the 1-position is called Lespedamine, 1-MeO-DMT. With an NO bond, this should be classified as a substituted hydroxylamine. I would love to know if anyone anywhere has ever tried smoking it. I suspect it might very well be active, but it is, to my knowledge, untried. -Alexander shulgin TIHKAL)

•4,5-methylenedioxy-N,N-Dimethyltryptamine (4,5-MOD-DMT)
(Because positions 4 and 5 are your key positions for substitutions on the DMT molecule I would be very interested in learning if this compound is active in humans. As of now there does not exist any published human bioassays or any reports of human pharmacology, but because of this comment made about the closely related compound 4,5-MOD-DIPT "25 mg, orally) Nothing much happened for about 3 hours, and then I suddenly shot up. I was at the plateau for a fair time, the recovery was difficult to define chronologically. This was in daylight; I was reminded very much of LSD." I am hopeful that 4,5-MOD-DMT will be an active and novel psychedelic compound.

I have also had very much interest in using ULM-491 (1-methyl-d-lysergic acid butanolamide) as a primer to DMT because of these comments that Alexander shulgin in TIHKAL: "A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities to be symptom free. With several of the experimental subjects in this study, the DMT was preceded by the administration of 1-methyl-d-lysergic acid butanolamide (UML-491), a potent serotonin antagonist. This was given either orally (1-2 mg 30 to 40 minutes before) or intramuscularly (0.5 mg 10 minutes before). This served to greatly intensify the effects of the DMT, with intense and agitated hallucinations, highly intensified colors, and a more extreme loss of time and space perception. It was assumed that UML-491 was inactive, but recent trials indicate that there can be central effects produced. It is discussed in the entry for LSD."
From what I can glean from shulgins statements ULM-491 greatly intensifies the effects of DMT when taken prior to its administration.

I'm currently researching several other DMT homologues but feel that I'm getting too far off topic by bringing them up here, IF not I would be glad to discuss them in detail.

Thank you for your response,

-EG

The UML-491 study is here: http://link.springer.com/article/10.1007%2FBF02153861

Hope you can read German!

Looking at the wiki entry:

So it sounds like ongoing usage would be a bad idea.

" 40 normale Personen bekamen DMT; der resultierende psychotische Zustand wurde beobachtet und registriert, 15 von diesen Versuchspersonen wiederholten das Experiment nach Verabreichung von Antiserotonin (UML-491). Das Antiserotonin hatte eine stark potenzierende Wirkung auf die experimentelle Psychose. Dies könnte die bekannte Theorie unterstützen, wonach der psychomimetische Effekt der halluzinogenen Stoffe, wenigstens teilweise, auf Antiserotoninwirkungen beruhen soll. "

40 NORMAL people were given DMT wich reulted in a psychotic condition . The antiserotonin strongly potentiated the experiMENTAL psychosis . This could strengthen the theory that some of the effects of DMT could be caused at least partly by antiserotonin .

The german wiki says that the word " psychomimetische ": doesnt exist .

In english ---- >

" Psychotomimetic

A drug with psychotomimetic (also known as psychotogenic) actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to just hallucinations. Psychotomimesis is the onset of psychotic symptoms following the administration of such a drug. "

= Backward people and not scientists .

Here's the TIHKAL paragraph mentioning ULM-491 as a DMT primer in English:
A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities to be symptom free. With several of the experimental subjects in this study, the DMT was preceded by the administration of 1-methyl-d-lysergic acid butanolamide (UML-491), a potent serotonin antagonist. This was given either orally (1-2 mg 30 to 40 minutes before) or intramuscularly (0.5 mg 10 minutes before). This served to greatly intensify the effects of the DMT, with intense and agitated hallucinations, highly intensified colors, and a more extreme loss of time and space perception. It was assumed that UML-491 was inactive, but recent trials indicate that there can be central effects produced. It is discussed in the entry for LSD.

-EG

What is this "anti-serotonin" you are speaking of?

Psychotomimetic is an out-dated and inaccurate term, as psychedelics DO NOT mimic psychosis.

It said "found that the administration of 40 mg quantities ( of what?) to be symptom free"
Meaning nothing happened (ok, was he saying 40mg administrations of ULM-491 we inactive or was he talking about DMT?)

But, when the patients were given ULM-491 prior to the administration of the DMT, the DMT did produce effects, the ULM-491 May have even made the effects more intense than a standard DMT experience.

ULM-491 is a 5ht2b receptor antagonist and is a partial antagonist at the 5ht2c, but acts as a partial agonist to several other serotonin receptors.

I'm guessing it's (ULM-491) antagonist action at the 5HT2c receptor frees up that receptor for the DMT, but honestly I have not put very much research into this topic, it was shulgins comments that led me to look into ULM-491 as a primer to DMT, but it's not a top priority area of research for me, and I'm not so clear on shulgins statements, I'll have to sit down and review all this in depth when I have more time...

-EG

It said...."found that the administration of 40 mg quantities to be symptom free"
Meaning nothing happened, it did not produce a psychotic condition.

Psychedelics do not mimic psychosis, I don't want to get into it here, but more thoughtful nomenclature has been established as a result of psychotic conditions and the psychedelic state being two completely separate and unrelated phenomenon.

-EG

" Das Antiserotonin hatte eine stark potenzierende Wirkung auf die experimentelle Psychose. Dies könnte die bekannte Theorie unterstützen, wonach der psychomimetische Effekt der halluzinogenen Stoffe, wenigstens teilweise, auf Antiserotoninwirkungen beruhen soll. "

I dont see the bit you are talking about and it conflicts with the quote above . It says that the antiserotonin had a strong potentiating effect on the psychosis = trip .

Try typing in "psychotomimetisch

(Gives redirect to "Modellpsychose".)


Looks like you worked out that was another term for UML-491, based on its antagonist effects at certain of the 5-HT receptors. The idea that this antagonism relates to the observed potentiation of DMT effects is AFAIK untested, at least in comparison with any other comparable 5-HT antagonists.

https://en.wikipedia.org...ethysergide#Pharmacology

Methylergometrine: "According to Jonathan Ott, methylergonovine [a synonym] has LSD-like actions above 2 milligrams[citation needed]. Clinical dosages are ten times lower."

So the metabolism of 40mg of, presumably, UML-491 produces less than an equivalent of 2mg of methylergometrine in the appropriate pharmacokinetic timeframe Maybe??

This perhaps begs the question, what are the interactions of methylergometrine (and, uh, other ergolines?) with DMT? And do we really need to find out?

A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities to be symptom free...

Here's the quote where he said it was symptom free(above)....

Correct me if I'm wrong but is shulgin saying:
40mgs DMT was symptom free
But when ULM-491 was given prior, the 40mgs of DMT produced intense psychedelic action.

Is it possible that the ULM-491s antagonism at the 5ht2c receptor is "freeing" that receptor up for the DMT? DMT being a 5ht2a and 5ht2c receptor agonist (as well as sigma-1 and some other partial agonist action at other receptors) or is the ULM-491s partial agonist action at other serotonin receptor sites playing a role here?

Here's the shulgin clip in English one more time:

A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities to be symptom free. With several of the experimental subjects in this study, the DMT was preceded by the administration of 1-methyl-d-lysergic acid butanolamide (UML-491), a potent serotonin antagonist. This was given either orally (1-2 mg 30 to 40 minutes before) or intramuscularly (0.5 mg 10 minutes before). This served to greatly intensify the effects of the DMT, with intense and agitated hallucinations, highly intensified colors, and a more extreme loss of time and space perception. It was assumed that UML-491 was inactive, but recent trials indicate that there can be central effects produced. It is discussed in the entry for LSD.

Sorry if I had more time it would be easier to analyze all this, but as I said before I'm very busy, and this topic is very very low priority for me as far as research goes.

If someone could make very clear exactly what shulgin was saying this would be much easier.

-EG

In the early clinical studies of DMT and DET, frequent use was made of schizophrenic patients, in the belief that if these drugs imitate the mental disorder in normal subjects, the use of schizophrenic population might be especially informative, either through some enhanced response or a loss of effect. One clinical study with a group of female patients (with 1.0 or 1.5 mg/Kg DMT being administered, presumably by intramuscular injection) showed a delayed onset (doubling of time), a relative freedom from autonomic effects, and an absence of hallucinations. I truly admire the logic patterns that allow the construction of a research study that will have it either way. Positive effects, our hypothesis is supported. Negative effects, out hypothesis is supported. Do schitzys get better or do they get worse? See? We were right.

A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities to be symptom free. With several of the experimental subjects in this study, the DMT was preceded by the administration of 1-methyl-d-lysergic acid butanolamide (UML-491), a potent serotonin antagonist. This was given either orally (1-2 mg 30 to 40 minutes before) or intramuscularly (0.5 mg 10 minutes before). This served to greatly intensify the effects of the DMT, with intense and agitated hallucinations, highly intensified colors, and a more extreme loss of time and space perception. It was assumed that UML-491 was inactive, but recent trials indicate that there can be central effects produced. It is discussed in the entry for LSD.

The second paragraph is the relevant one but perhaps the paragraph above it will make it somewhat easier to understand what shulgin was saying....

-EG

40 mg was symptom free?! They really screwed up somewhere with the administration of their doses...

Back on the UML-491, its potentiating effects could come from a number of factors, perhaps allosteric modulation at one or more of these receptors. We probably don't know much about its interactions with the sigma receptors either.

Currently, I'm only in a position to speculate Someone out there, please be inspired!

Shulgin never specifies the ROA for those 40mg DMT doses.

DOSAGE : >350 mg (orally)
60 - 100 mg (intramuscularly)
60 - 100 mg (subcutaneously)
60 - 100 mg (smoking)
4 - 30 mg (intravenously)
(A.Shulgin; TIHKAL)

I'm guessing the ROA was intramuscularly, in which case 40mg very well may have been symptom free. (...Or at least nearly symptom free, again no part of what shulgin says is very specific)

There's a lot of areas where I feel shulgin could have been more specific in order to avoid confusion.

-EG