A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities of DMT 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. (-Shulgin;TIHKAL)

So is shulgin saying that ULM-491 taken shortly before DMT administration intensifies the effects of what would otherwise be an inactive dose? If this is the case I would love to know more. Have there been any other studies performed in which ULM-491 was used as a primer to DMT?

Ulm-491 information: UML-491, Methysergide, Sansert. This is the synthetic homologue of methergine (1-methyl) and is employed clinically as a treatment for migraine headaches. When the usual therapeutic dosage of two milligrams is scaled up by a factor of ten, there is a profound LSD-like response described by most subjects. A number of these ergot analogues from nature can be considered as potential precursors for the preparation of LSD. But here, there is a 1-methyl group that is effectively permanently attached, so it cannot play this role. (Shulgin;TIHKAL)

If anybody has any information regaurding ULM-491 being used as a primer to DMT please let me know. I spend a good deal of time in study of tryptamines, phenethylamines, and lysergamides, so when I hear of studies being conducted that are using two novel compounds from these chemical classes simotaneously, I naturally try to find out all that I can.

Hmm Fascinating. I read TIHKAL and PIHKAL but do not remember Shulgin mentioning this
ULM-compound nor it's DMT-potentiating effects...but then again there is SO much info in
those books it could have easily slipped my mind.


IIRC DMT gets absorbed into our brain's Serotonin-receptors as though it were a sort of
surrogate Serotonin. This ULM-491 could be a serotonin agonist by means of unblocking
Serotonin receptors blocked by endogenous Serotonin Antagonists, allowing more Serotonin
to be absorbed by your Serotonin receptors.

I can imagine that with these extra Serotonin-receptors available, more DMT than usual is also
able to be absorbed by these receptors and thus greater effect is achieved.



However this is all guesswork. I don't know via what actions this ULM-491 is a Serotonin-Agonist.
Googling for it, I found nothing at all (except this very topic)

ULM-491 has a short paragraph in the LSD extentions and commentary section in TIHKAL.

Shulgin mentions ULM-491 as a primer to DMT in the DMT extentions and commentary section of TIHKAL.

Both mentions of these compounds in TIHKAL were incredibly sparse, and like you said when one attempts to do further research online nothing can be found, which is why I posted here, I'm very thorough in my research and will only resort to posting on forums when I cant find ANY other information.

I had similar ideas as to the pharmocological action between these two compounds, I would love to find some scientific data to confirm this, but at this time it doesn't appear to exist.

Ill keep doing research, if I find anything ill post it here.

Thank you for your thoughts and interest.

While re-reading this old post I realized that I butchered this compounds code name by placing the M and the L in the wrong order...

It's interesting to look back even just a year or two and see how much my knowledge and organization has improved, most people don't think you learn that much in the span of a few years...but trust me, it can make world's of difference, some of these older posts are pretty embarassing.

Any way, UML-491 (1-methyl-D-lysergic acid butanolamide) was the compound I was speaking of, I apologize for the multiple errors I made in this compounds code name.

I still recall there being something of interest here, so I want to review:
From TIHKAL in the DMT extensions and commentary section:

*meaning non-schizophrenic individuals, as schizophrenic patients in research were being discussed just prior to this paragraph
**of DMT
So, when combining 1-methyl-d-lysergic acid butanolamide with DMT, "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" as the above states...

I was curious, were these inactive 40mg administrations of DMT becoming active when combined with 1-methyl-d-lysergic acid butanolamide? The article states found that the administration of 40 mg quantities to be symptom free, was this mentioned because the these same 40mg administrations produced effect when combined with 1-methyl-d-lysergic acid butanolamide?

Here's a review of UML-491's excerpt from TIHKAL's LSD entry:


1-methyl-d-lysergic acid butanolamide is an antagonist at the 5-HT2C receptor as well as the 5-HT2B receptor, it serves as a partial agonist at 5-HT1A , and is thought to have partial agonist effects on other 5-HT receptors...

And apparently has an active metabolite:




Then researching 1-methyl-d-lysergic acid butanolamide in relationship DMT still turns up very little...

"The Hallucinogens" By A. Hoffer and H. Osmond mentions DMT and uml-491 on page 460...page 491 the hallucinogens (link may not work)

This excerpt briefly mentions it...




Can anybody find a english article of "The effect of antiserotonin on the experimental psychosis induced by dimethyltryptamine;A. Sai-Halász; Sai-Halász, A. Experientia (1962) 18: 137. doi:10.1007/BF02153861 " ???


http://link.springer.com...ticle/10.1007/BF02153861
This is what I could find, and as the quotation box below demonstrates, it is not in English...


Ok, I'll leave this short spurt of research here for now, however I do feel that there is some interesting research here...

-eg

I think the language of 'agonist' and 'antagonist' is getting mixed up here.

Simply put, an agonist is a molecule that switches the receptor to it's 'active' conformation, causing a signal to propagate through the cell. Serotonin is that natural agonist of it's receptors, and drugs like DMT act as exogenous agonists, binding to the same receptor and triggering a similar activation.

An antagonist binds to the receptor but does not change it's conformation to 'active' - it's just like gum in a keyhole, meaning that other drugs cannot effect the receptor.

A serotonergic agonist will generally inhibit the psychedelic effect of a drug like DMT - this is why people can take things like quetiapine to abort a psychedelic trip. The antipsychotic has a higher affinity for the receptor than the psychedelic and so blockades it.

Now, there are TONS of serotonin receptors, so it's possible that this ULM drug might act as antagonist of some serotonin receptors while acting as an agonist (and thus potentiating activity) at the psychedelic-specific serotonin receptor (2A), but if so, that would be a pretty interesting combination.

Now, there are drugs called allosteric modulators that bind to different parts of the receptor to make it more sensitive to an agonist (an example of this is alprazolam, which binds to GABA receptors and makes them more receptive to endogenous GABA without acting as an agonist or antagonist itself). Perhapse ULM is a positive allosteric modulator of the 5-HT2A, but given it's shape, my guess would be that it fits into the active site attacked by serotonin and DMT.

It may have other activity - maybe it's some kind of MAOI or other metabolic enzyme inhibitor. These studies may also simply be erroneous and need a follow up.

Blessings
~ND

Hmmm...

The posted pharmacological data for 1-methyl-d-lysergic acid butanolamide is correct, as confirmed by the following sources...
Sandoz Laboratories Basle.
“Methysergide (UML-491), a new serotonin antagonist”.
Scientific Exhibit, Federation of American Societies for Experimental Biology. 1960 April;
Abstract
UML (with the generic name methysergide) is a highly effective and highly specific serotonin antagonist. It may be used in affections in the pathogenesis of which serotonin might be of importance. Favorable results were reported especially in migraine and other vascular headaches. As a further indication primary chronic joint rheumatism and related affections, allergy and Raynaud's disease are mentioned. . Chemically UML (1-methyl-lysergic acid butanolamide) is a closely related to Methergine (lysergic acid butanolamide), but is pharmacologically significantly different. Its toxicity in animal experiments is much lower (LD50 i.v. in rabbits 28.0 mg/kg, Methergine 2.6 mg/kg). The oxytocic effect on the rabbit uterus in situ is 16 times weaker than that of Methergine. . The antiserotonin effect of UML is in vitro on the isolated rat uterus, 4000f that of LSD (Methergine 73.5%). The effect is highly specific, since on this experimental object the antagonism of UML towards serotonin is 9200 times stronger than that towards acetylcholine. In vivo UML proved superior to LSD etc. in experiments on rats which were given UML or LSD and the sensitivity of the isolated uterus of these animals to serotonin was tested. The serotonin edema of the rat paw is antagonized 4.4 times stronger by UML than by LSD. The strong antiserotonin effect on the intact animal is demonstrated also on the inhibition of the pressor effect of serotonin in dogs, as well as on the inhibition of the barbiturate- potentiating effect of serotonin in mice. The barbiturate-potentiating effect of chlorpromazine is not influenced by UML, an indication of the specificity of its serotonin antagonism.
https://www.ncbi.nlm.nih.gov/pubmed/8743744
https://www.ncbi.nlm.nih.gov/pubmed/2933009
Methysergide has been shown, in vitro and in vivo, to inhibit or block the effects of serotonin, a substance which may be involved in the mechanism of vascular headaches. Serotonin has been variously described as a central neurohumoral agent or chemical mediator, as a "headache substance" acting directly or indirectly to lower pain threshold, as an intrinsic "motor hormone" of the gastrointestinal tract, and as a "hormone" involved in connective tissue reparative processes https://pubchem.ncbi.nlm...acology-and-Biochemistry


*1-methyl-d-lysergic acid butanolamide is an antagonist at the 5-HT2C receptor as well as the 5-HT2B receptor, it serves as a partial agonist at 5-HT1A , and is thought to have partial agonist effects on other 5-HT receptors...

And apparently has an active metabolite:




Apparently psychedelic effects are induced by an active metabolite...(as described above)

I thought that was interesting as well, why would a 5HT2c antagonist potentiate the effects of DMT?

Is it partial agonism at other serotonin receptors?

An active metabolite?

Is uml-491 acting as a allosteric modulator as suggested by ND?

Could it be other suggestions proposed?

It would help to be able to access an English version of some of these original studies using uml-491 as a primer to DMT... can someone find an English version of this article?


-eg

After reading it over, I can glean a Good deal without actually knowing the language, it's really not that hard, and you can use the internet to translate words which are not obvious either by form or context...

Though an actual translation would be nice...

-eg

9,10-Didehydro-N-[1-(hydroxymethyl)-propyl]-D-lysergamide

This is the metabolite of UML-491, and I figured it's pharmacology was relevant...



I'll post better information when I have more time...

I'm still searching for an English translation of:

Cite this article as:
Sai-Halász, A. Experientia (1962) 18: 137. doi:10.1007/BF02153861"
"The effect of antiserotonin on the experimental psychosis induced by dimethyltryptamine
-A. Sai-Halász"

-eg