Gaboxadol

[Limpet_Chicken]

Assuming it was pure (or almost so) ibotenic acid.

All is not lost. Mods, I hope this isn't classed as stepping over the line, but the identical process occurs in Amanita muscaria when the mushroom is heat dried for use, and that reaction in that context has been discussed openly.

Ibotenic acid decarboxylates to muscimol when heated, a good boil should do the trick.

AFAIK some ibotenic acid if ingested will be metabolised to muscimol itself, but as is, it is a glutamatergic neurotoxin, but little passes the BBB, although if I recall a previous discussion I had in this forum, the conclusion was arrived at (possibly by myself, I can't remember for shit these days) that it may undergo active transport through the blood brain barrier.

Dropped for abuse reasons? FFS, that is rediculous as grounds. If that is good reason to shitcan something new and promising, and going from my experience with muscimol on sleep, and on endurance, then it really would be something to have brought out, then how do they expect to ever bring out new dopaminergic stimulants, or opioids.

 

[hamhurricane]

I have read that it does cross the BBB, and when injected into the striatum it causes serious damage at doses low as 10µg. How is it, then, that people ingest 100mg+ doses of ibotenic acid seemingly without toxic effects and why have has amanita muscaria use never been linked to cognitive deficits? This is scaring the shit out of me.

 

[Limpet_Chicken]

Hmmm, localised microinjection into a specific area is one thing, diffuse neurotoxicity spread out over a wider area is likely to be another in terms of actual phenotypically expressed deficit.

E.g 10mg ibotenate direct into the CA1 zone of the hippocampus, bilaterally, and the poor bastard it happens to is going to be left a disabled, amnesiac vegetable, that same 10mg taken by mouth or injected IV, then some will be pissed out probably, some will get turned into muscimol, some may be protein-bound (unsure, I have no data on plasma protein binding of muscimol or ibotenic acid), then some will get through into the brain, assuming it is actively transported as supposed, where instead of going straight to the vital bits and buggering things up left right and center in one specific area, it causes more of a nasty poking all over with a pointy spoon, than a targeted shot to the head with a 20mm armor piercing round from a high velocity rifle.

A.pantherina on the other hand, unlike A.muscaria, now that one I refuse to take, I have A.muscaria here, and I do have a pretty bad memory problem (although I do heat cure my amanitas, and only take ones I wild-craft myself, or taken from friends who do the same) and avoid any potential glutamatergic neurotoxins like the plague (as one should anyway, but doubly so in my case)

Never had them cause any memory impairment whatsoever, surprising really, given the orthosteric GABAa agonism of muscimol too, but there you have it.

A.pantherina DOES have some infrequent, but nevertheless present reports of memory impairment, and contains considerably more ibotenic acid and muscimol both, than A.muscaria, however, and it is a BIG however, it contains two neurotoxins, stizolobic and stizolobinic acid, which act as kainate receptor agonist type excitotoxins, structurally these are not too far away from the acromelic acids, which are a series of compounds present in certain fungi of the genus Clitocybe, notably C.acromelalga and C.amnoelens, and which cause on ingestion, a severe and persistant allodynia, also notable about the acromelic acids, is the truly shocking potency, acromelic acid-A, exerts toxicity at the fucking attogram level! people were doing evil things to rats with it at 50 aG/kg.

Now that is to me, more than enough reason to avoid A.pantherina entirely, even without any reports I could find of evoked persistent allodynia.

 

[MurphyClox]

First, thanks a lot for your warning Hamhurricane!

Second, I agree with pal Limpet: Ibotenic acid converts into muscimol upon heating; so at least you're left with this one. Better than nothing but not the real McCoy. But I would rather recommend something like 'dry' heating and not boiling the substance. Put the stuff into an oven, turn on the heat to 60-70°C (described conversion temperature is 60°C) with the oven's door slightly open. I think one should wait several hours then. Check the conversion rate with TLC (detection with ninhydrine reagent).


@Astavats: Nope, there is no way I can think of that ibotenic/muscimol gets transformed into gaboxadol resp. the other way around. The compounds may have a similar structure but synthesis and reactivity are too different. Now that I said 'synthesis', we should better stop with further details. In any case I'd like to see this thread stay open.

With regard to the toxicity I'm convinced that neither gaboxadol, nor muscimol nor ibotenic acid can't be a serious problem. In particular the latter two were used extensively and still are today. There would have been reports about long-term side-effects otherwise. It's somehow comparable to the cannabis-story, but lets not get into further details but rather stay on topic.

Amanita pantherina is doubtless the worse choice, compared to A. muscaria.


- Murphy

 

[Astavats]

As always, I appreciate it Murphy.

 

[Limpet_Chicken]

Hm, perchance not murph, whoever heard of a siberian shaman with a laptop in his yurt and a bluelight account/erowid posts

Never heard of orthosteric GABAa agonists being addictive either, which is quite surprising, they do NOT generalise in the rat model for either barbs, benzos, alcohol, or Z-drugs, and in my own person experience using the mushrooms, no withdrawal syndrome was noticed, I would have expected quite a nasty one potentially if somebody went meph-head with the stuff.

I find the lack of generalisation to zolpidem and zopiclone interesting too, as those are perhaps THE most similar drugs to an Amanita trip, that I have encountered pharmacologically, not exactly bum-fuck buddies, but cousins certainly doing activities considered indecent, at least subjectively.

As for A.pantherina, I would not touch it with somebody else's permission to borrow F&B's famed fecally tainted stick. Those stizolobic and stizolobinic acids are apparently metabolic precursors in the Clitocybe species allodynia-inducing fungi, and if the mushrooms can do it, I do not wish to find out if human meat can or will do so in vivo, and I would even be reticent to some degree about extracts, unless extremely carefully produced and cleaned, a few stray femtograms of something undesirable might prove enough to make one suffer greatly, going from the Clitocybes (what a name ey? :/ ), I recall something on the order of a couple of hundred uG of acromelic acid A was isolated from 17 kilograms of fungi, not much, until you consider that scary potency.

 

[golden1]

I know this is slightly offtopic, but would benzos potentiate muscimol? It seems like they would, but I've never seen reports of it.

 

[MurphyClox]

I haven't seen such reports either but it is highly likely that at least some aspects of the pharmacological action of benzodiazepines are potentiated by muscimol. The former are positive allosteric modulators, the latter is an agonist. So why not?!

In any case would I not encourage such a combo!


- Murphy

 

[Phener]

A sample of Gaboxadol was analyzed with MS and found impure with the primary constituent being ibotenic acid. The sample contained no Gaboxadol. This is obviously very dangerous - anyone who has purchased this chemical should be extremely careful not to ingest it.

This makes me physically sick. I guess with no regulation this kind of s**t happens.

Classic case of Supply & Demand economics. There is ENOUGH of a demand out there for gaboxadol that people will supply "IT" at any cost. @Murphy - I am suddenly feeling your wise words

 

[Solipsis]

When receiving this I should be getting an NMR analysis with it. Not expensive either by the way. I could provide it after scanning that if anyone is interested.

It sounds like something to be careful with, even more than most funky chemicals we eat of which is known more.

 

[MurphyClox]

When receiving this I should be getting an NMR analysis with it. Not expensive either by the way. I could provide it after scanning that if anyone is interested.

*raiseshandslowly* 1H-, and if anyhow possible, 13C-NMR, too.

 

[Solipsis]

*raiseshandslowly* 1H-, and if anyhow possible, 13C-NMR, too.

Hereby provided

But note the solvent is not CDCl3 but methanol-D4.

Compound is a flaky clean white solid. Not a fine powder.
I am excited to try this after I have analyzed the spectrum myself (absolutely no time for such things now), after verification starting at a few mg or perhaps a diluted formal test first.

 

[Hammilton]

Like anything, I'd be extremely careful regardless of documentation. You could literally be trusting it with your life.

 

[hamhurricane]

Solipsis I can say with almost total certainty your material came from the same source as mine, I had my friend (who is an incredibly skilled chemist) do the analysis and it was ibotenic acid. Do not trust the vendor on this matter until you have independent verification. I know you already said this but I just want to re-emphasize.

 

[Solipsis]

Alright then, thanks! If it were muscimol then it'd be okay but I obviously would not want a neurotoxin!

I started trying to analyze if you look at the second picture but I could not seem to match it. Not even the number of protons... Let me check if it is ibotenic acid then...

Weird! The vendor is otherwise very professional...

 

[Solipsis]

This doesn't seem like it would be ibotenic acid to me - the peaks most on the right look like they are at least a quartet to me, meaning we would be looking for a proton with 3 neighbours. There are none of those in ibotenic acid, right?

But as you can see in my partial 'analysis' gaboxadol does not fit either because there appear to be 4 peaks and gaboxadol has 5 different protons.

At a first glance muscimol fits, let me see if I can assign the proton peaks - then verify with elecronegativity ppm values

 

[MurphyClox]

Ok, some first quick notes regarding the 1H-NMR:

- Yep, methanol as the solvent is obvious, it is even noted on the spectrum ("CD3OD"). But methanol's residual signal comes at 3.31 ppm (what was assigned to be C(5)H2) and water in MeOD at 4.87 (what was assigned to be "MeOD").[1]

- It's a shame that the person who recorded the spectrum did not note the numerical values of the integrals, and neither the exact chemical shifts of the fine signals. While the former ones can be derived easily from the graphical integrals, the signal splitting can only be guessed to a certain degree, considering the picture's low resolution.

- Usually gaboxadol is prepared as hydrobromide salt.[2] Hence, we speak theoretically about 4 signals á 2 protons (3xCH2, 1xNH2+), and further 2 singuletts that together make up 1 proton (tautomery equilibrium between amide-like and enaminol-like-form of the isoxazole! I would be surprised if this wouldn't be seen at 300 MHz).
BUT: Easily exchangeable protons can disappear in protic solvents, hence it's probable that the signals for NH2+ and the proton caught in the tautomery equilibrium do not appear. This leaves us with the signals marked as 6, 7 and 8 in the spectrum. Signal "8" is indeed the methylene at pos. 8 (no neighbouring protons = singulett; chemical shift also confirmed by a simple prediction using ChemDraw), and the remaining signals supposed to be 6 & 7 equal the positions C(5)H2 and C(6)H2.


Looks not too bad at first sight. I'll see if I can find a genuine reference for comparison tomorrow.
Until then, somebody please provide a good reason to believe that the shown spectrum actually belongs to Solipsis' sample. As it seems to come from the same vendor who took the piss out of Hamhurricane, I wouldn't believe it... Call me paranoid, I don't care.


Peace! - Murphy


[1] The most relevant reference in this respect: JOC 1997, 62(21), p.7513
[2] I checked it again and it looks like depending on where you buy, the hydrochloride seems to be common, too.

 

[Solipsis]

Thanks a lot! My analysis skills are quite rusty as you can see ...

Apparently I can get another NMR on request, I will ask for the values - indeed when I did my own NMRs those were always added, and the resolution was never this low.

Hamhurricane please clean up your mailbox, I will not mention the vendor by name but it would be good to find a subtle thing that will confirm we are talking about the same people and also I would love to hear about anything else about your experiences with this sample you got and the way it was dealt with.

Also, I would be very surprised to get this kind of service while they would in fact be selling me a neurotoxin at a laugable price. WTH. But the possibility of this makes me very apprehensive. I wonder about the thermostability of gaboxadol because I feel like 'curing' any possible ibotenic acid to make sure I dont die or fall into a coma or something - even though the doses are different!

 

[indelibleface]

Isn`t ibotenic acid only neurotoxic when administered intracranially? When people consume fly agaric (as far as I remember) they cook it to convert the ibotenic acid into muscimol, but I would think some ibotenic acid remains, right? Are these people causing themselves damage, if ibotenic acid is neurotoxic by oral administration?

Warning: I could be completely talking out of my ass here.

 

[MurphyClox]

Ohhh man, we are getting far into synthesis here. Anyway, let me word it this way: Freshly collected fly agaric mushrooms are dried preferentially at 50-80 °C in a household oven, which is kept slightly open, until they are crispy dry. This should apply to pure ibotenic acid, too. As long as we speak about a gaboxadol-salt, I don't see a major problem in this respect. I have not seen any stability studies either*, but to me there are no obvious labile moieties in gaboxadol which speak against treatment at this temperature. I think that in either case concomitant drying over a hygroscopic salt could help the process, as moisture facilitates decomposition (...partially dissolving some of the salt, which in solution is in an equilibrium with the free base, which itself is susceptible to oxidation).


Peace! - Murphy


* Edit: Let me add that in the original patent from 1978 the melting temperatures of the hydrobromic salt and the free compound (zwitterion) are 162-163°C and 242-244°C, respectively, and in both cases accompanied by decomposition. Even the fist value is twice as high as you need to 'cure' your ibotenic acid.