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Help me find the most potent/least toxic alcohol

Synaps3

Synaps3

Bluelighter
Joined
Sep 14, 2011
Messages
257
So I am still looking for the most potent least toxic alcohol. I need someone who knows more about pharmacology to tell me what alcohol should be the best.

I posted about this a while ago and someone suggested the cyclopropyl, but wasn't sure. Also I'd rather not completely inhibit the oxidation - just slow it down. The problem with the well known 2m2b is it gets hydroxylated so fast that the good effects only last about half an hour and then it just makes you sleepy. That's why the ethynyl is more potent.

I need to replicate the ethynyl without being toxic?

I have a diagram here that explains the problem:

15dlwjm.jpg
 
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Yes, both the cyclopropyl and isopropyl will slow oxidation. Making that carbon quarternary will prevent oxidation entirely, so the tert-butyl is another oxidation although that might end up with quite a high half life. The main problem with these is possibly affecting pharmacodynamics more than you want to.
 
Alcohol is well studied and in moderation has little negative effects , why even bother?
 
Even tert-butanol causes kidney and bladder damage in animal toxicity studies, so we can't equate slow oxidation with low toxicity. I wonder if the mechanism of that urogenital toxicity is somehow similar to what chronic ketamine use does...

http://www.ncbi.nlm.nih.gov/pubmed/1397807
 
The 8-ethynyl analogue of pyrazolam mimics alcohol almost perfectly. A guy who drank 1l of gin per day took 30, 3mg tablets, felt no need for alcohol, woke up with no hagover (a first for 8 years).
 
Even tert-butanol causes kidney and bladder damage in animal toxicity studies, so we can't equate slow oxidation with low toxicity. I wonder if the mechanism of that urogenital toxicity is somehow similar to what chronic ketamine use does...
Click to expand...

I'm not saying that slowing the oxidation directly lowers the toxicity. It indirectly lowers it because the potency is increased, so you take less.
Tert-butanol has no place to be oxidized. AFAIK the only way it can be metabolized is by glucoronidation, which is extremely slow.
I hope that's the reason it's toxic though because if not, that would mean 2m2b would likely be toxic to those organs as well.

Alcohol is well studied and in moderation has little negative effects , why even bother?
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Because it bothers me that the most easily accessible legal drug is also one of the most toxic to the body.

I think an entirely different drug that mimics alcohol without being an alcohol itself would be ideal, but try to find one drug that hits GABAab, NMDA, and inhibits breakdown of 5-HT. Try to even find a drug that hits only GABA and antagonizes NMDA at the same time.

The problem is that all modern drugs are way too selective, so you have to either make a combination or find a less shitty small drug that will mimic alcohol - that's what I'm doing.
 
Synaps, am not aware of any studies showing alcohol has negative effects in moderation.

Also, as far as I know alcohol is not directly nuerotoxic.
 
polymath said:
Even tert-butanol causes kidney and bladder damage in animal toxicity studies, so we can't equate slow oxidation with low toxicity. I wonder if the mechanism of that urogenital toxicity is somehow similar to what chronic ketamine use does...

http://www.ncbi.nlm.nih.gov/pubmed/1397807
Click to expand...

I experimented with tert-butanol a few times. The active dose (with no GABAergic tolerance) was around 10 ml, the effects lasted for well over 10 hours. It was pleasant at first, but as it started to wear off, especially the next day, I noticed some hangover symptoms. One evening I took 20 ml and the next day I was feeling really shit, like a pretty severe ethanol hangover. Haven't been able to find information about why that might be. I wonder why 2M2B seems to lack hangovers, since there's only a methylene difference between the two. (I haven't tried 2M2B myself)
 
^ When I was a teenager, and not old enough to buy booze, I tried even isopropyl alcohol maybe 2-3 times, with doses from 25 ml to 50 ml. The 50 ml dose felt similar to about a sixpack of 4.5% ABV beer. It was a quite disgusting experience, because a few hours after ingesting the stuff I could smell the acetone it was metabolized to in my own breath, and that smell/taste of acetone lasted about 24 hours. Not very recommendable, though, because large doses of IPA can cause bleeding in the stomach or hemolysis (breakdown of red blood cells).
 
I've tried isopropanol as well, and the acetone breath indeed is pretty annoying. Higher doses resulted in a splitting headache the next day, assuming due to the acetone.

I've actually tried a lot of solvents. That's what happens when you have free access to them and are a little bit too curious about drugs.
 
^ I've tried toluene, ether and chloroform as inhalants, but the last time was about 10 years ago. Unbranched-chain hydrocarbons like n-heptane didn't seem to work (note that n-hexane should never be tried as an intoxicant, it causes peripheral axonopathy even more quickly than other solvents cause neural damage).
 
^ toluene, diethyl ether, petroleum ether, THF, 1,4-butanediol, ethyl acetate (not sure why, I was drunk to start with).

@OP: a cyclopropyl moiety is a lot more reactive than regular alkyl or cycloalkyl groups, so it could increase toxicity.
 
THF was a disappointment too. As sekio said in that thread, it takes ages for the GHB metabolite to build up, and larger doses (>5 ml) were, first of all, a bitch to drink, and second did produce noticeable hangover-like symptoms the next day. Being a strong solvent, I felt that my GI tract took quite a beating after a few weeks of semi-daily use. But I'm getting off-topic, sorry.

E: as a side-note, I did notice a diethyl ether-like dissociative-esque quality to the experience shortly following the ingestion, which slowly changed into a typical GABAergic sedation/anxiolysis.

E2 @ OP: perfluoro-tert-butanol, how about that, eh?
 
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diethyl ether-like dissociative-esque quality
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Inhalants and 3rd plateau DXM doses always put me in a similar strange mental state, that I can't remember much about when I'm sober, but if I take something that gets me there, I immediately recognize it like "Hey, I'm in this place again, been here many times before". There's always a very strong feeling of deja vu associated with that, like another BL:er described in this thread.

stirfry said:
When I enter the déjà vu, it's like being hit with this sudden realization (epiphany like even) that I have been in this very moment before, and in fact, this eternal moment is my true reality. It seems as if my whole life leading up to this moment is just an illusion that I've tricked myself into believing, and I can see that I am in an endless cycle of living this illusory life all the way up to inhaling the nitrous and finally coming to the great realization while knowing I will soon forget this truth, and I will soon start the cycle all over again by returning to that false life (sobriety).
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But related to OP:s question, a thing that bothers me about high-potency alcohols, is that if someone tends to always lose control when drinking and ends up downing more alcohol than was intended, it would be very easy to drink a life-threatening amount of something like 2M2B. With ethanol you at least start to feel sick if you drink too quickly, which kind of makes it safer.
 
How well is this danger comparable with those of GHB which obviously has a narrow index for 'blackout' overdosing but at the same time I think to die from it directly the toxic dose is quite a bit higher. I've heard about people (like dubious ex-'friends') chugging bottles and surviving, one with a deathwish and another actual friend completely by accident. Although people surviving isn't saying that much about safety considering how easy one can aspirate etc. That is not what I mean.

I've tried 2M2B realizing the above threat, but relativised it thinking of GHB. I have extensive experience with GHB and while I always took the risks seriously I have blacked out from it having gone *just* a bit too high or from overlapping effects etc, but only very rarely and definitely not in very inappropriate situations. Blackout would not be the right word I guess, it was more like hypnotic doses which I have also taken intentionally often enough. Felt sick as a dog from it sometimes but never really as if I put myself in danger. With 2M2B something like this happened one time. It sure is tricky.

But: how much more dangerous is acute toxicity and risk of death when comparing EtOH, GHB, 2M2B and others like 1ECH? Apart from blackouts, aspirating etc, how easy would it to just die directly from the toxicity?

Does it matter here for example on what GABAa subtypes the drug acts?

http://www.bluelight.org/vb/threads/488399-Least-Toxic-Most-Effective-Most-Concealable-Alcohol/page2

TI for ethanol is ~ 5
For 2M2B someone in that thread calculated ~17 times so I guess that compensates slightly for the potency.. :)
Now what are some for the other compounds
 
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Does it fubar your CYP450 like the desmethyl version of that apparently does?
 
I had a conversation with the guy who wrote all the journal articles pertaining to CYP450 alkylation. He was surprisingly helpful and seemed to be interested in my questions (I didn't even expect an answer).

Anyway, he said that as long as the alkyne is not terminal, it does not cause damage to the P450. Alkyl groups longer than propyl in these tertiary alcohols has been shown to decrease the potency. Ethyl is actually the best, however it gets oxidized too quickly, so that's why the ethynyl helps the potency. The best solution would likely be to put a methyl on the end to make a propynyl. It may reduce the potency slightly, but should still be better than 2m2b and less toxic than the ethynyl.

Alfa-Aesar stocks it, but for a much higher price.
http://www.chemspider.com/Chemical-Structure.200616.html

a cyclopropyl moiety is a lot more reactive than regular alkyl or cycloalkyl groups, so it could increase toxicity.
Click to expand...

Would it still be better than the ethynyl though? Because the guy I talked to indicated that the cyclopropyl would not cause a problem with the enzyme; it might still be more toxic though idk.

There was an article written in the 50s (sorry no link)
Hypnotic Activity of Some Tertiary Alcohols 1
BY SEYMOUR L. SHAPIRO, HAROLD SOLOWAY AND LOUIS FREEDMAN

It shows the therapeutic index of the 2-cyclopropyl-2-butanol (called cyclopropylmethylethyl in the article) is the best and the second best is the 1-ethynyl-1-cyclohexanol, but I think it was chosen to be used in pharmaceuticals because its index was only slightly lower and its duration of action was 3.5 hours compared to 2 hours with the cyclopropyl. However, they seem to indicate that methylpentynol (the ring opened version of ECX, as only 1 hour, but I'm pretty sure it's the same duration as 2m2b.) It looks like they are measuring solely based on "hypnosis" though, so the entire duration of action may be longer.

I am thinking about synthesizing the cyclopropyl in my lab and testing the effects. The propynyl synths are a bit too hard for me though, so I'm not going to make that one.
I am not super experienced, but I have access to analysis equipment and I'm not reckless.

Do you think ingesting the cyclopropyl would be more harmful than the 2m2b or ECX (assuming it is pure)?
 
Sorry I don't know about 1-cyclopropylcyclohexan-1-ol

What about this one:

bicyclo%5B2.2.2%5Doctan-1-ol.png


bicyclo[2.2.2]octan-1-ol

or 1-adamantanol for that matter? (no info in MSDS)
 
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