Help me find the most potent/least toxic alcohol

[Synaps3]

Can't find any info on that either, however, the 1-adamantanol:

mouse LD50 intraperitoneal 600mg/kg (600mg/kg)

compared to 1-Ethynylcyclohexanol:

mouse LD50 intraperitoneal 500mg/kg (500mg/kg)

That doesn't say much about the actual potency, though.

1-cyclopropylcyclohexan-1-ol

I was referring to 2-cyclopropyl-2-butanol earlier, but that one could be OK too, but with my limited knowledge, I think that the non-cyclohexanol based tertiary alcohols should have at least somewhat shorter half-life. I think the half-life on the cyclohexanol ones is probably getting a bit too high - especially when adding so many carbons. It may also be steering in the direction of higher selectivity and to mimic alcohol, you want the least selectivity.

But who knows, I'm a novice to this pharmacology stuff anyway, so feel free to correct me.

BTW: This is my favorite site to look up info like LD50 etc (better than MSDS info):
http://chem.sis.nlm.nih.gov/chemidplus/

 

[Synaps3]

...but anyway, if someone could answer the question in my previous post about the 2-cyclopropyl-2-butanol, I'd really appreciate it. I don't want it to get buried in the thread.

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

I am thinking about synthesizing the cyclopropyl in my lab and testing the effects.

 

[Pomzazed]

Sometimes cyclopropyl can "open" and undergoes addition just like alkene.... I dont like this much.

 

[belligerent drunk]

^ yes, a cyclopropyl moiety can behave as a pi double bond, which can undergo a number of reactions that normal alkyl groups don't. I don't have any particular examples of possible toxicity, just sayin'.

 

[polymath]

^ Cyclopropane itself was used as an inhalation anesthetic decades ago, but it was replaced with other compounds because you needed to have as much as 80% of cyclopropane in the inhaled gas mixture before it made one completely unresponsive to pain. And also because it's flammable, of course. Does that alkene-like reactivity apply to plain cyclopropane?

Edit: apparently it reacts with bromine to form 1,3-dibromopropane (ring opening)... http://www.chemguide.co.uk/organicprops/alkanes/halogenation.html

 

[Pomzazed]

Cyclopropane structure has high internal energy due to bond angle which it doesnt like.
sp3 carbon wants to have 109.5 degree angle, but cyclopropane bends it to 60 degree!

That makes cyclic strain in there, and orbital canNOT bend to 60 degree, which makes it
Looks like bent banana bond ready to open out (google "Banana Bond" and "Bent Bond" for more info)

Plain cyclopropane wont open that easily at room temperature by itself, but not in petroleum distillation process.
Plain cyclopropane only opens when attacked by strong reagents like halogens.
Substituted cyclopropane can be more or less stable to ring opening depending on electron withdraw/donate of the group, and also steric demand of the group.

 

[belligerent drunk]

^ Cyclopropane itself was used as an inhalation anesthetic decades ago, but it was replaced with other compounds because you needed to have as much as 80% of cyclopropane in the inhaled gas mixture before it made one completely unresponsive to pain. And also because it's flammable, of course. Does that alkene-like reactivity apply to plain cyclopropane?

Edit: apparently it reacts with bromine to form 1,3-dibromopropane (ring opening)... http://www.chemguide.co.uk/organicprops/alkanes/halogenation.html

A little bit off-topic, but I find it somewhat interesting how buprenorphine and naltrexone behave as weak partial agonist or antagonists at the MOR, similarly how naloxone and nalorphine are antagonists at MOR. In the case of the latter pair, they have N-allyl groups, in the case of the former pair, they have N-cyclopropylmethyl groups (typical opioid agonists have N-alkyl) - which I believe is responsible for the antagonist/weak agonist properties of the compounds, and also demonstrates how a cyclopropyl moiety can behave as a regular C=C bond, at least when it comes to receptor binding.

 

[Synaps3]

Substituted cyclopropane can be more or less stable to ring opening depending on electron withdraw/donate of the group, and also steric demand of the group.

Do you know what would happen in the case with the alcohol?

If it were to open, it would form a vinyl group, right? That was part of the drug ethchlorvynol (similar tertiary alcohol) so it probably wouldn't be too bad.

 

[MeDieViL]

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

Every ghb addict often blacked out, during this blackout ppl can choke on their tongue or on their own puke which wont be the case for alcohols, also the glutamate toxiticy wont be a issue.

low potent opiates togheter with ghb cause life threatening breathing issues 5ht4 agonists prevent the potential of dying during a opiate overdose which makes me wonder wheter they can make GHB a safer drug, that said GHB can be taken daily every evening without ever getting physical addicion, or used for sleep for that matter, look at narcolepsy, ppl disagreeing with this got under the grips of the potential severe mental addiction and went over that treshold, also ghb is the only drug associated with long term, like forever anhedonia, i was the first member here to point out the toxiticy of ghb when everyone tought it was non toxic search for my old threads.

i used it daily every evening for years without issues didnt use it for sleep as it woke me up couldnt sleep on it lol however because of combining it with a severe stim overdose well some sort of weird autoimmume strange stim reaction causing severe heartpain and other issues so i kept on taking gbl to knock me out of that horror to prevent death, if viagra or other things failed, yeah i was a complte idiot at 21 and the combined damage of that stim with the excitoxiticy of gbl gave me partional seizures everytime i took it also sensitive to seizures induced by phenibut or baclofen i can no longer take gbl, i was having 20 seizures a day or so and it damaged my willpower to only take it 6 hours a day, probably because my brain was fucked for several months.

That said, 2m2b diluted in water togheter with a low dose of a toxin and something with a extremely bad taste and voila, ppl wont druk to fast and puke, no alcoholics drinking till they die, or hangovers, and i consider the high far superior.

However if this stuff comes in the hands of rapits we have severe problems, except the rapists, especially if they add in mdpv, cant taste that in a nice mint drink, serieusly that drug shouldnt be available.

 

[belligerent drunk]

Do you know what would happen in the case with the alcohol?

If it were to open, it would form a vinyl group, right? That was part of the drug ethchlorvynol (similar tertiary alcohol) so it probably wouldn't be too bad.

It's more likely that it would not just open by itself, but open as a result of a chemical reaction similar to an alkene (electrophilic addition for example). So a cyclopropyl moiety can be seen as analogous to a vinyl moiety as far as chemical behaviour goes. Not that it is too terribly reactive, but definitely more so than regular alkyl/cycloalkyl groups. Some drugs do have cyclopropyl groups, like buprenorphine, without it being a big problem as far as I know. However, in the case of the alcohol, you have to consider that the dosage would be at least a thousand times higher, so the likelihood of it being a problem increases.

 

[Solipsis]

Every ghb addict often blacked out, during this blackout ppl can choke on their tongue or on their own puke which wont be the case for alcohols, also the glutamate toxiticy wont be a issue.

low potent opiates togheter with ghb cause life threatening breathing issues 5ht4 agonists prevent the potential of dying during a opiate overdose which makes me wonder wheter they can make GHB a safer drug, that said GHB can be taken daily every evening without ever getting physical addicion, or used for sleep for that matter, look at narcolepsy, ppl disagreeing with this got under the grips of the potential severe mental addiction and went over that treshold, also ghb is the only drug associated with long term, like forever anhedonia, i was the first member here to point out the toxiticy of ghb when everyone tought it was non toxic search for my old threads.

i used it daily every evening for years without issues didnt use it for sleep as it woke me up couldnt sleep on it lol however because of combining it with a severe stim overdose well some sort of weird autoimmume strange stim reaction causing severe heartpain and other issues so i kept on taking gbl to knock me out of that horror to prevent death, if viagra or other things failed, yeah i was a complte idiot at 21 and the combined damage of that stim with the excitoxiticy of gbl gave me partional seizures everytime i took it also sensitive to seizures induced by phenibut or baclofen i can no longer take gbl, i was having 20 seizures a day or so and it damaged my willpower to only take it 6 hours a day, probably because my brain was fucked for several months.

That said, 2m2b diluted in water togheter with a low dose of a toxin and something with a extremely bad taste and voila, ppl wont druk to fast and puke, no alcoholics drinking till they die, or hangovers, and i consider the high far superior.

However if this stuff comes in the hands of rapits we have severe problems, except the rapists, especially if they add in mdpv, cant taste that in a nice mint drink, serieusly that drug shouldnt be available.

People on EtOH overdose can certainly aspirate choke and die, they often enough do - and I highly doubt it's less likely than with something like G by comparison, so I don't understand why you claim it couldn't happen with alcohols? The main difference would perhaps be that there is a wider error margin with EtOH before arriving at the hypnotic unarousable point - dosing that high on EtOH is just not as common or consistent as G addicts let it happen but that doesn't mean it's not potentially equally dangerous, if one does throw up in that state. And we'd have to factor in how usual it is to throw up on too much alcohol vs. a hypnotic G dose.

Yeah when I started taking G the idea was that it was miraculously non-toxic but over time concerns and alarms were raised and I am glad I got out in time and apart from some bouts / stretches of daily use I didn't keep it up for years, more like three periods within one year, and after quitting the 3rd time it was conclusive. I don't know about the anhedonia, and while I have issues I don't attribute them to an apparent dysthemic type disorder that may have been caused by G. So, lucky I guess. I do think that I'd rather have those 3 stretches I did with no raised dosage, than one stretch with upping the dose - cause that sounds really frightening although I guess one can taper and manage.

You propose something like denatonium, but in a way that would be agreeable to dose once but not to keep redosing? Good luck with that, I think if it's possible to ingest without thinking "this is NOT worth it!", then alcoholics won't be deterred to abuse it - seems naieve. *Maybe* to avoid date raping, but honestly I don't think a dose is as 'benignly minty' as you make it out to be - it's so volatily camphorous that I doubt you could mask it without raising wild suspicion. Granted I never tried to slip it in a "creme de minthe" to test it out on myself or anything like that (I don't think double blind date raping experiments are a thing ).

I agree that pure 2M2B should not be made easily available or widely available (though cannot comment on whether if diluted to match alcohol doses, it wouldn't be superior to EtOH - wouldn't it?), but I don't think G should be either. There is absolutely no tolerance for casual use of undiluted compounds of that potency, especially if you consider how many people are already overdosing on EtOH.

 

[Synaps3]

Yeah when I started taking G the idea was that it was miraculously non-toxic but over time concerns and alarms were raised and I am glad I got out in time and apart from some bouts / stretches of daily use I didn't keep it up for years, more like three periods within one year, and after quitting the 3rd time it was conclusive. I don't know about the anhedonia, and while I have issues I don't attribute them to an apparent dysthemic type disorder that may have been caused by G. So, lucky I guess. I do think that I'd rather have those 3 stretches I did with no raised dosage, than one stretch with upping the dose - cause that sounds really frightening although I guess one can taper and manage.

Same for me, but I ended up finding that it is probably toxic, just in a different way. I found that doing GHB twice a day (never 24/7), my muscles got very spastic and it got harder for me to find a dose to get high. In the beginning, the window between being high and passing out was pretty large, but it quickly got to the point where I only had like 200mg of window space. I was up to 4g twice a day and if I took 4.2g, I would uncontrollably pass out. The other weird thing about G is that you don't feel much and then next thing you know, you're passed out. With alcohol and 2m2b, it isn't like this. I've taken high doses and gotten sleepy, but I always had control of going to sleep or not.

It seems like G taken by people without narcolepsy, gives them narcolepsy. One time I was sitting at my computer writing something while on G (about 4g I think) and I felt fine. Next thing I know, I woke up with my nose smashed into my keyboard and bleeding lol, then I remembered how my head just started nodding uncontrollably beforehand. I mean - think about the velocity required to make my nose bleed. It's like it completely disables your muscles (or even forces them down lol).

I am not saying that G is a bad drug or anything, I just don't think it's something you can take very often or in social situations unless your tolerance is really low and you have a very accurate measure of the dose. Despite the similar potency of 2m2b, there is much more margin for error (even after using for a while).

Anyway, my reason for finding this alcohol is not just as a substitute for ethanol, but also as a high quality sedative. I really don't like modern sedatives very much (benzos) because they make me forgetful and dumb and they feel like shit compared to old drugs. These tertiary alcohols have a very strong sedative effect with minimal mental effects and that's what I like about them so much.


So I'm going to make the cyclopropyl in my lab soon. Any objections? speak now.

 

[belligerent drunk]

^ I don't understand why you want to go for the cyclopropyl-containing one. Surely if you want sterical bulk, then you can use other alkyl substitutions?

 

[Synaps3]

^ I don't understand why you want to go for the cyclopropyl-containing one. Surely if you want sterical bulk, then you can use other alkyl substitutions?

In the article I referenced earlier, it was the most potent one and in other articles I've read if the number of carbons on one branch of the alcohol exceeds three, the potency begins to decrease again, so I thought cyclopropyl would be the best. Do think there would be a better substitution that would have the same potency?

BTW: is a vinyl chloride more reactive than just a normal vinyl with carbons?
I ask this because ethchlorvynol had a vinyl chloride in it and it wasn't too toxic (probably not good), but people used it for years.

Not that I plan on using a vinyl chloride, I'm just thinking that if they got away with that, then I can get away with a normal vinyl (and that's also assuming the cyclopropyl opens up in the first place).

 

[Limpet_Chicken]

Theres a few pretty sketchy looking (and in some cases just plain fucked up, paraldehyde for instance...YUCK!) examples of oldschool downers with plain dodgy looking substituents or backbones. Ethchlorvynol, chlormethiazole, glutethimide (fucks with corticosteroid synthesis, the relative of it, aminoglutethimide is used in cancer treatment for this). And don't forget the granddaddy of all medical fuckups, thalidomide. Originally designed as a morning sickness drug and sedative for pregnant women. Didn't turn out too well did it now..oops

It did lead to treatments for multiple myeloma though by way of redeeming itself at least partially (lenalidomide. I know someone who takes it and probably is still alive because of it He's not likely to get pregnant though any time soon.....)

And re-vinyl halide, yes it is more reactive.


Then theres the likes of chloral hydrate and analogs of it, bromal hydrate used to be used, a century ago or two, although this was when the only alternatives were herbs, paraldehyde, and either sulfonal, trional or tetronal which are dangerous if they can bioaccumulate as they cause a chemically induced porphyria. Brominated analog of chloral is cautioned against in my copy of 'household physician' for being a real ripper on the innards. This from a book which gives directions on how to treat piles using nitric acid and directions for dosing teething babies with blue pill and grey mass (mercury and chalk), blue pill is a mercurial also, calomel was in these books liberally spattered around, as were antimonials and arsenicals like fowlers solution, and lead based stuff like goulard's lotion, based on lead acetate, or as they knew it then, sugar of lead.

The only truly safe and effective remedies they had of that kind, sedatives were mandragora or its relatives, and opium.