Gaboxadol

[MurphyClox]

...there is no 1H-NMR-spectrum of gaboxadol or any of its salts available, measured in MeOD, anywhere in the literature. I could provide melting points though, if these are of any help.

- Murphy

 

[Solipsis]

Respect!

Oh for what it's worth I don't see how synthesis has anything to do with our discussion,
I mean we are not talking about reactions to make it here that are not quite plain, only perhaps the relationship between gaboxadol, muscimol and ibotenic acid.

 

[Hammilton]

I don't think discussions of decarboxylating a compound via heating has ever been considered synthesis discussion. There have been dozens regarding marijuana and THCA to THC and CBD to THC.

 

[MurphyClox]

Ok, thx for clearing this out.

 

[Solipsis]

I just read that

Nielsen and coworkers independently explored the nonenzymatic
decarboxylation of ibotenic acid, reporting that it was stable in water
even at 378°C overnight and only after its exposure to boiling water at pH
extremes over the course of several hours was any decarboxylation to muscimol
noted.

but everyone I can find quotes the same thing and there is no publication I can dig up or access at this moment for that matter.

Apparently some UV wavelengths initiate/catalyze the conversion and it's possible to use other solvents than water to facilitate this.

Can anyone clear this up? I would still like to contact ham-hurricane, I never got any subsequent communications from the gaboxadol source...

It would be a shame if I would have to let it rot away for safety, a sure-fire way to convert possible ibotenic acid at least enough to lessen the amount to what one might find in Amanita mushrooms would be helpful. If it destroys the gaboxadol that would explain no effects, if I get 'discernable effects' when I start approaching 6 mgs when titrating belonging to muscimol I know what is going on...

 

[MurphyClox]

Stable in water at 378 °C? Must be a typo. I assume you meant 37 °C.

If they studied the nonenzymatic decarboxylation, it suggests that in the mushroom this reaction could take place with enzymatic catalysis. And in that case are 50-60°C for 2 days absolutely reasonable. At some point the enzymatic reaction must stop due to lack of water and maybe denaturation of the decarboxylase, but obviously does the procedure work quite good.

However, if one got pure ibotenic acid and not a biological sample, it could indeed get a bit tricky. I was always under the impression that the decarboxylation happened without the aid of any catalyst. As a first suggestion , I'd recommend boiling the sample in water for 2-3 hours (start low, with e.g. 500 mg in 10 ml water; use a condenser to trap the vapor). If it is within one's possibilities, I'd also recommend to close the vessel and connect the upper end of the condenser with a vessel filled with excess Ba(OH)2-solution. Place an inflatable balloon somewhere on the apparatus, to allow volume expansion. The barium solution will effectively trap any produced CO2 as insoluble carbonate salt. Of course, beware of any cross-contamination! Barium is very toxic.

If the above procedure doesn't work a sample of genuine ibotenic acid, I would be really surprised. The barium-carbonate-trap is probably kinda overkill for this purpose... The solubility of carbon dioxide is already significantly lowered in boiling water, hence, it will be driven out anyway.

TLC-control of the process would be a good idea. Detection of both ibotenic acid and muscimol can be achieved with ninhydrin.


Peace! - Murphy

 

[Solipsis]

Elaborate approach as ever, thanks for the support

Refluxing is definitely a possibility for me, I wonder though if it's not much easier to use KOH instead of Ba(OH)2 considering the toxicity and price. Better yet NaOH because I don't have to order that. You are probably right about the overkill though...

Unfortunately I have no TLC plates and a palet of solvents readily available so this might be one for the future but I don't know if I wanna be messing with ninhydrin...

Anyway the toxic dose for ibotenic acid is 30-60 mg - so I should be able to stay well under that starting with very low trials, if there is no muscimol-like or gaboxadol-like activity at the expected dose I should just stop...
That is, in the event that the decarboxylation did not work.

I should point out though that I quoted the 378 °C correctly (so: sic...) but it's unclear if it is a typo in the original literature, we should assume not and therefore the problem remains.

 

[MurphyClox]

If you really want to apply a CO2-trap, barium chloride/hydroxide is the thing to go. Barium carbonate is insoluble in water and will precipitate (thus removing CO2 from any equilibrium), while the solubility of potassium and sodium carbonate is not suitable for this application at all.
But yeah - total overkill for this application...

I should point out though that I quoted the 378 °C correctly (so: sic...) but it's unclear if it is a typo in the original literature, we should assume not and therefore the problem remains.

Could you please name the citation?


- Murphy

 

[Solipsis]

Could you please name the citation?


- Murphy

That's the thing: I can't really find the article that is quoted on sites like this here:

http://www.entheogen.com/forum/showthread.php?t=11709

I think I found about 7 more that all took the same excerpt but that doesn't mean anything at all on the net: they probably all copied it from the link above. Just use some google skills to find those other sites, they're not journal sites or anything and the quote is verbatim.
It's mentioned to be written in "the following article" but no link is given, yes as a guy with a scientific background I would also have to say: then we're basing this all on no evidence at all, but I'm tempted to say that the excerpt was not pulled out of someones ass-hat so to speak.

 

[raybeez]

Ibotenic Acid Decarboxylation to Muscimol: Dramatic Solvent and Radiolytic Rate Acceleration

Filera CN, Lacya JM and CT Peng

Synthetic Communications 2005 35(7):967-70.

Both ibotenic acid (1) and muscimol (2) have been isolated from several fungal species including Amanita muscaria1 and are active CNS agents of the NMDA and GABA receptor systems respectively. It has also been demonstrated that under certain circumstances 1 can decarboxylate to 2, but the scope of the reaction was largely unexplored.2 A number of years ago colleagues in our laboratory, likely influenced by the conditions of the classic Krapcho reaction,3 first reported in a talk that simply stirring 1 in a solution of DMSO with high specific activity 3H2O overnight at ambient temperature afforded a very reasonable radiochemical yield of 3a with exclusive tritium incorporation in the amino methylene as established by tritium NMR.4 Since then we have performed this simple yet robust synthesis many times, providing valuable radioligand 3a to the neurochemical community and supporting literally hundreds of key published studies in the GABA area. A representative synthesis is described in the experimental section.

Years later, Nielsen and coworkers independently explored the nonenzymatic decarboxylation of ibotenic acid, reporting that 1 was stable in water even at 37°C overnight and only after its exposure to boiling water at pH extremes over the course of several hours was any decarboxylation to 2 noted.5 Until recently we were unaware of this surprising observation and it clearly demonstrates that our mild ambient temperature decarboxylation of 1 to 3a with DMSO/3H2O is a far more intriguing and remarkable result than first recognized. It is certainly a rare event to so markedly accelerate a reaction by a mere solvent change6 and we were prompted to further examine this interesting transformation more closely.

We first confirmed and extended the observation of the Danish workers, noting that when 1 is dissolved in D2O at ambient temperature and monitored by HPLC, it is stable for more than two weeks, showing only minimal (0.2%) conversion to 3b. We next examined the stability of 1 in DMSO-d6 and D2O (10:1), a concentration identical to the tritiation reaction. In this solvent system at ambient temperature and monitored by HPLC, approximately 90% of 1 was gradually and fairly cleanly converted to 3b over the course of a week. This result was repeated several times and interestingly shows that the addition of DMSO to water clearly facilitates the decarboxylation of 1. However, and perhaps even more important, the use of 3H2O (in lieu of water) with DMSO dramatically accelerates the decarboxylation process.

 

[MurphyClox]

Raybeez beat me to it. That's the source. And the citation from "Nielsen and coworkers" is:

Elsebet Ø. Nielsen, Arne Schousboe, Steen H. Hansen, Povl Krogsgaard-Larsen
"Excitatory Amino Acids: Studies on the Biochemical and Chemical Stability of Ibotenic Acid and Related Compounds"
Journal of Neurochemistry 1985, 45(3), pp.725–731
DOI: 10.1111/j.1471-4159.1985.tb04052.x

Abstract
The complex pharmacological profile (excitation/inhibition) of ibotenic acid on single neurons in the mammalian CNS prompted studies on the stability of ibotenic acid and a number of structurally related excitatory amino acids under different in vitro conditions in the presence or absence of enzymes. Ibotenic acid, (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA), (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and (RS)-α-amino-3-hydroxy-4-bromo-5-isoxazolepropionic acid (4-Br-homoibotenic acid) were all inhibitors of (S)-glutamic acid decarboxylase (GAD) in mouse brain homogenates, but only ibotenic acid was shown to undergo decarboxylation during incubation with brain homogenates. The formation of the decarboxylated product, muscimol, which primarily occurred in a synaptosomal fraction, was dependent on the presence of pyridoxal-5-phosphate (PALP) and was inhibited by (S)-glutamic acid, 3-mercaptopropionic acid (3MPA), aminooxyacetic acid (AOAA), and allylglycine, suggesting that ibotenic acid is a substrate for GAD. The overall decomposition rate for ibotenic acid (8.7 nmol min−1 mg−1 of protein), which apparently embraces other reactions in addition to decarboxylation to muscimol, was higher than the rate of decarboxylation of (S)-glutamic acid (3.2 nmol min−1 mg−1 of protein). At pH 7.4 and 37°C, but in the absence of enzymes, none of the excitatory amino acids under study underwent any detectable decomposition, whereas ibotenic acid and 7-HPCA, but not AMPA and 4-Br-homoibotenic acid, decomposed, partially by decarboxylation, at 100°C in a pH-dependent manner. In the presence of liver homogenates, ibotenic acid was also shown to decompose. Although muscimol was the only detectable reaction product, mechanisms other than decarboxylation may be involved. Under these conditions, the degradation reaction or reactions were partially dependent on PALP and were inhibited by AOAA and 3MPA but not by allylglycine. The present in vitro studies indicate that ibotenic acid is likely to undergo enzyme-catalyzed decomposition to give muscimol in brain tissue and after systemic administration to animals. These aspects must be taken into consideration in the interpretation of the pharmacological or neurotoxic effects of ibotenic acid after direct application near central neurons, after local injections into animal brains, or after systemic administration to animals.

Edit: I just saw that this article was already quoted in the link that Solipsis provided. Nonetheless, here come the most relevant points:

Solutions of the excitatory amino acid ibotenic acid [...] in 0.2 M potassium phosphate buffer, pH 2.7,7.4, and 10.0, were kept at 37°C for 24 h without any observed decomposition.
[...]
Ibotenic acid [...] stored for 2 h at 100°C [...] was quantitatively decarboxylated to muscimol at pH 2.7.

Peace! - Murphy

 

[Solipsis]

Great! So a typo gets cited and recited etc, reminding of that game where a number of people have to whisper a message in a chain and it get's seriously distorted. Man the internet is crawling with distorted nonsense...
378 Did sound like a ridiculous number... Perhaps not for kelvin but ok.

Back to the topic at hand: many many thanks for finding that one for me - it sucks that I am not registered at the lab anymore (or were you able to view this for free? Think not right?)

I don't think there is any reason to believe that quenching a pH 2-3 solution of muscimol would revert to ibotenic acid right? Probably a silly question, I would be quite surprised.

Well this makes the refluxing conversion quite easy. There is hope after all.

 

[Solipsis]

Oops double, got a timeout error?

 

[MurphyClox]

Back to the topic at hand: many many thanks for finding that one for me - it sucks that I am not registered at the lab anymore (or were you able to view this for free? Think not right?)

Access to the J Neurochem is no problem, the article from Synth Comm was kindly provided by a fellow on another board. Both journals do not offer free access though.

I don't think there is any reason to believe that quenching a pH 2-3 solution of muscimol would revert to ibotenic acid right? Probably a silly question, I would be quite surprised.

Yeah, silly question The CO2 will leave the reaction mixture. There's no way it will get attached back onto muscimol. If carboxylation was that easy, you'd get a price for it!

Seems like instead of gaboxadol you are very close to have some muscimol at hand soon. You own my envy, Solipsis, seriously! I expect a detailed trip-report in return as kinda thank-you.


Peace! - Murphy

 

[Solipsis]

Access to the J Neurochem is no problem, the article from Synth Comm was kindly provided by a fellow on another board. Both journals do not offer free access though.


Yeah, silly question The CO2 will leave the reaction mixture. There's no way it will get attached back onto muscimol. If carboxylation was that easy, you'd get a price for it!

Seems like instead of gaboxadol you are very close to have some muscimol at hand soon. You own my envy, Solipsis, seriously! I expect a detailed trip-report in return as kinda thank-you.


Peace! - Murphy

Haha, well that may take a while since I am on a break mostly from such mind altering drugs. If it is actually gaboxadol and more confirmed and less doubted then I would have run some trials earlier.

Still if you have some patience I'm sure that report will be there. Seems like either gaboxadol or muscimol are quite typical... hard to miss.

I really do wonder what it is I have, got 2C-N together with this and it was equally cheap, remarkable. But it's a bright yellow substance as it should be.
The stupid thing is scammers often enough know exactly the right things to say, pretty much just like the best genuine vendors, like: yes it's the nitrate salt like I suspected and that it formed from the 2C-N nitration. But one time I got scammed quite some time ago communication stopped as soon as they got the money, and it was substantial - something of interest to a scammer.
Nothing makes sense, they did send me things that seem right and they were very pleasant to deal with but ham-hurricane was almost sure I got a toxic compound instead of what they say.
Who scams someone for no money at all and sends them poison??? I'd very much like to talk to ham-hurricane about it though it should obviously be as least as possible like vendor discussion.

I have other reasons to believe they are the real deal since they had quite rare things from time to time. I'm so confused. If you guys think I should delete most of this post, so tell me but I hardly think it does any harm?

 

[ManRider]

Well, I took the plunge and tried 10mg of the gaboxadol. Sure enough, it seems to be the real thing. I felt very drowsy and tired, and not much else.

 

[Solipsis]

Well I'm glad you're okay. Thanks for reporting!

Seems like ham got my panties in a bunch for nothing, together with yours and perhaps other.

I'm curious about how you would evaluate this stuff, is it useful as a sleeping aid without significant after effects next day? Are there any upsides if you compare this to the drowsiness of some sort of benzo (I don't know which you are familiar with)?

Right now I use midazolam but my sleeping issues don't seem to be that substantial anymore thinking of how I feel before taking the mida.
If need be I would definitely be interested in substituting with gaboxadol.

 

[hamhurricane]

Seems like ham got my panties in a bunch for nothing, together with yours and perhaps other.

This behavior reminds me of the DOB-DFLY/2C-BFLY mixup, the moment it was suggested that the chemical might not cause immediate death users started ingesting it. We all got this from the same vendor. The vendor did not do the analysis themselves - they told me this. They did not synthesize it, it came from a secondary source. I had it independently analyzed by a trusted friend and he found it to be ibotenic acid - even if I'm wrong why on earth would you take that risk for a meager sedative high? And then use lack of immediate side effects as evidence for it's safety - surely you know that means absolutely nothing?

This sort of gullibility/blind trust is exactly why vendors have an easy time taking advantage of their customers.

 

[Solipsis]

I was not all that convinced we got it all from the same place, moreover you went silent twice after dropping that comment. Now, I got confidence in your rep but what are we to think?

And the reason to possibly take the plunge for manrider and me would be that the toxic dose of ibotenic acid is higher than the active dose of gaboxadol, so you should be able to determine which of the two it is (if it isn't a third compound... my god) without wreaking havoc. And apparently uncooked amanita intoxication includes enough noticable effects to stop titrating this sample when some weird nausea is felt or something entirely unexpected.

Notice how I say titrating and how the DOB-DFly / 2C-B-Fly mixup had casualties from people jumping in the deep end?

10 mg of ibotenic acid should be manageable for manrider but my already prepared samples are around 2, 5 and 10 mg if I am not mistaken (I would have to check): I would start lower than that.

If it is ibotenic acid how do you explain manriders drowsiness?

If you are claiming it's something else I am very thankful if there is something to it ham, seriously, but could you please tell what the method of analysis was and generally a little more information than basically only saying "It's something else, trust me"?
I don't want to get into vendor discussion too much, even if it is harmless the way we do it, but they said that this secondary source they got this from is the same as the source the research was done on.
I hate to make a habit of blindly trusting vendors but this one has had a good history with a good number of other independent people I have contact with. Which makes me think that if it is not gaboxadol they don't know it themselves.

It doesn't make a whole lot of sense and manrider's post and now yours again makes it all the more confusing. I wouldn't ingest it until more gets cleared up, but I was having doubts about whether it actually is the same vendor.
Yes it's rare but I couldn't say with such confidence that we got it all from the same place like you do.

My reason for wanting to try this is not at all a sedative high of any kind but as an effective sleep aid that doesn't have the negative properties other GABAergics have... the Z-drugs raised expectations but apparently came up short and are more similar to benzo's than people said initially. (in terms of dependence etc).
Anyway I didn't want to get so defensive and with a good reason you are right to say it's not worth the risk, admitted.
Whatever the real story here I find all the signals terribly confusing and most of all conflicting.

EDIT!

Oh I am so sorry, only just saw you commented on this. A bit unfortunate timing, I will have to take back what I said about falling silent and perhaps a couple other things.
Thanks for the help!

 

[ManRider]

My rational to plunge in and ingest was this:
Gaboxadol is plenty active at 10mg according to clinical reports. Ibotenic acid, on the other hand, gives significant psychoactive effects at 50-100mg. Furthermore, ibotenic acid does not cross the blood brain barrier very effectively, and its more so muscimol which results in psychoactive effects, so the potential of taking 10mg of ibotenic acid was overall not very threatening.

I grant the possibility that it could have been some other compound altogether, but the odds of a similar compound being dangerous at 10mg seemed very low. On top of all this, I do trust the vendor I obtained the stuff from, though I realize that vendors slip up sometimes.


Here's how the experience went:
I took a gel cap of 10mg of this stuff at about 9pm at night. I hoped that it would help me sleep, as I have suffered from mild sleep problems for some months. Perhaps it would have other interesting or fun effects, but I wasn't really expecting any.

Within 20 minutes I started to feel it and within 40 minutes it seemed to more or less hit the plateau of effects. I felt drowsy and tired, both mentally and physically. As far as downers go I've tried a variety of benzo's, GBL, alcohol, 2m-2b, mild opiates, carisoprodol (soma), a variety of herbs, and maybe some other weird things I'm forgetting. More than anything, the effects of this "gaboxadol" reminded me of the drowsiness/tiredness that comes with alcohol, without the other effects, except for maybe a hint of disinhibition. The effects were not particularly pleasant and at least with this dose it was not recreational. You'd get a more enjoyable buzz from a beer or a little xanax if that's what you were after.

The next day I didn't feel extra rested, but i did not sleep better than usual and i was running a sleep deficit which i did not spend enough hours asleep that night to recover from. I also felt like some of the tiredness from the drug was lingering during the day, but I feel inconclusive about this part because I often feel tired when not getting enough sleep for a dew days (duh). I also find myself to be more sensitive to sedating/tiring effects from some drugs (e.g. benadryl, alcohol, etc.) than other people i know, so it could have been that.

Overall, I find benzos to be more effective sleep aids for me. They quiet my mind and help me stop thinking when i'm trying to relax. gaboxadol, somewhat like alcohol, gave me a tiredness without especially quieting my mind. That said, alcohol only rarely aids my sleep (and if it does its often in conjunction with cannabis), and if i go to bed after having a few drinks or more it will more often than not give me shittier sleep than if i were sober.

I will probably explore this stuff further since I have a gram of it. a smaller dose in conjunction with another sleep aid could be useful. perhaps at higher doses it becomes more recreational, but i suspect the sedation limits how enjoyable it could really be.