• N&PD Moderators: Skorpio | thegreenhand

1-Ethynylcyclohexanol *LOG*

The minimization calculation on my 5+ year old Dell Optiplex took less than a second. As expected, the structure was altered along with the corresponding CD file. The resulting space-filling orbital image looks a bit odd with a cleft in the middle left side.

CICUTOXIN_3_D-2.jpg


CICUTOXIN_3_D_space_filling-2.jpg
 
My computer is not modern then :(

btw, i still think alkynes aren't a good idea... They like to stick to many things permanently (covalently).

Could be that the alkynyl groups contribute a lot to the toxicity of these toxins. Having them conjugated apparently makes them more reactive.

Check out the Wikipedia article on polyynes: https://en.wikipedia.org/wiki/Polyyne#Biological_origins. Lot of interesting toxic compounds with 2 & 3 conjugated alkynyl groups. It's interesting to speculate about the apparent ancient origins of this feature as it is found in both plants & insects.
 
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Cyclohexanol with an ethynyl:


If you replace the alcohol with a carbamate you get ethinamate, which sounds like a Miltown derivative. And if you sort of double that carbamate into some thing I don't know the name, you get clocental, a sedative from the early days of Bayer.


But OP, who at least survived another fifteen months before going silent, has what is probably the metabolite of that. I don't know how carbamate muscle relaxers interact, but it seems like the crucial moiety, the very essence of their activity, is the carbamate part (and some loose alkyl groups).


Seems like this would be destined for conversion to cyclohexanone in your body (mildly toxic).


I think this chemical was on the market for its potential as a reagent for the arylcyclidine family, not as a chemical for personal oral research.





I am still alive, just did not use this site for some years and forgot my username now. So I'm using this new profile.


Ethinamate, Emylcamate, Miltown and many other old-school downers are alcohols (not barbs etc. of course). Most alcohols are liquid.
Emylcamate is 3-Methyl-3-Pentanol (+ carbamate) and that is a liquid when it's "decarbamated".
Ethinamate is Ethylnylcyclohexanol (+ carbamate) and that is not pure powder but some kind of "fibers" that will liquify in a temperature a little higher than room-temperature.
Miltown is also some kind of alcohol 2-methyl-2-propyl-1,3-propandiol + carbamate.
There are 100s of old carbamated alcohols, but I think none is in use anymore except Miltown and it's pro-drug Carisoprodol



The carbamate will make those substances into powder so they are more suited for medicine (as pills).
2M2B-carbamate was once on the RC market but carbamate is not just carbamate, it can turn a drug into something else then what it was before it became a carbamate, and because of 2M2B's small molecular-structure, I did not dare to try it.


I'm sure Ethinamate is much less toxic than EtOH but the CYP450 enzyme things it is capable of is strange.
I guess these are a less harmful version of Ethinamate?

https://en.wikipedia.org/wiki/Hexapropymate
https://en.wikipedia.org/wiki/Phenprobamate
https://en.wikipedia.org/wiki/Procymate


I did not include 1-ethynyl-1-cyclohexanol because, as I posted, I only found anectdotal information about it such as the trip report at the start of this thread. I was only interested in established drug molecules where I could find documented biological activity.
I would also stay away from 2M2B as its effects seem to linger into the next day likely due to the time needed to metabolize it for excretion.


Here is a link to an interesting paper on methylpentynol (Oblivon) toxicity including hallucinations: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2035981/



You can find more info about Ethinamate and also e.g. Methylpentynol etc. in Google Books, they have a lot of old books about medicine.
Haha, I agree 2M2B can have a very long duration. At least 12 hours. But feels more euphoric than EtOH and not as severe hangover as EtOH but the taste and smell of 2M2B is very bad!
I think Methylpentynol is an interesting substance, but the hallucinations scare me :p
 
Apparently the minimum requirement is four, not the previously thought five conjugated bonds for such noncompetitive polyyne GABA antagonists.

And Cicuta, is so toxic that a piece of root the size of a walnut is enough to kill a cow.

Also, either Oenanthe or Cicuta, is the origin for the term 'sardonic', coming from the Risus Sardonicus, or sardonic grin. Ancient Sardinian peoples, would ritually kill the old and infirm, as well as criminals sentenced to death, by poisoning with one of these water hemlock/hemlock water dropwort plants, followed by being battered to death, or being dashed against the rocks after being thrown off a cliff. The resulting muscular spasms, locking the jaw, and causing retraction of the facial muscles to expose the teeth, causing a ghastly imitation of a smiling death.

Despite what must be one of the most utterly nightmarish, horrific ways to die that mankind has ever deliberately caused another. What a way to go...jesus fuck me diagonally jumping jack christ on a bike.....fucking Hades' own shit, that is fucked up. Death by being beaten to death whilst in the throes of an agonizing death by terror-genic convulsant GABA antagonist....I'd extend such miserable, traumatic death only to my absolute worst enemies. I'd gladly see paedophiles and the filth both treated in such way, and rapists, but other than that, nobody deserves that as a way to go.

Oh, and methocarbamol survives in UK use to this day. I've had it prescribed a while back (years), and it just smelled funny and did a fucking miserable job as a myorelaxant with absolutely fuck all to suggest recreational potential.
 
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I actually find methocarbamol works pretty damn well as a muscle relaxant. It really doesn't do much else though, no sedation, anxiolysis, or euphoria.

Combine it with opioids and cannabis and it's nap time...
 
Hm, all it did for me (with actual muscle spasm due to nerve damage to deal with) was smell funky and taste like arse.

Tried it after baclofen as a first option, only to find out I'm a total nonresponder to ANY dose of baclofen, even by the fistful of tablets (10mg per), oral, plugged, nothing whatsoever, not even the tiniest bit of myorelaxation, whilst I've seen a former housemate (who quite honestly, I WISH had succeeded, fucking monstrous evil borderline klepto psychotic perditionslut) collapse after a most probable attentionwhoring parasuicide never intended to go as far as she did, totally paralyzed, I had to keep watch to ensure she continued to breathe, whilst she was unable to speak, and just BARELY able to speak with me in my second language, ASL sign, using fingerspelling at the time on her part)

Then, switched to tizanidine, a clonidine relative (I take both actually, alpha2 autoreceptor agonists just seem to agree with my body chemistry), and the tizanidine, at 4mg 5xdaily, orally will completely negate the otherwise intractable muscle spasm in my calf due to post-surgery nerve damage. Or even in the throes of opiate WD, if liquidized, at say, a ten strip of tablets, plugged, it'll stop the horrible akathisia, then put me right out for about five or six hours, just the sort of thing that is perfect for that last night before a script refill on my pain meds, when everything has worn off, unless I've done certain work to ensure it doesn't, or else made an expensive phonecall for an 8th or 1/4 of gear and maybe 50x5mg methadone tabs, to last the last two days when my pain meds have to be hoarded down to squirreled away little bits of the contents of oxy IR caps, siphoned off a few mg a capsule before taking them, but the tizanidine rx, now THAT is a muscle relaxer (and pretty strong hypotensive, so careful with it too), enough of one, plus adrenergic release inhibitor to hammer-blow opiate WD and get to sleep for that midnight vigil of eternal feeling wait-it-out whilst sweating bullets otherwise, if I don't have enough spare nitrazepam and chlormethiazole or bromethiazole to give myself the 1-2 punch that always serves to reliably KO me when neither will do so alone in such a situation.

Oh, and as far as alicyclic compounds with a conjugated polyyne alcohol 'theme' going on, allow me to throw this into the light.

Ladies and gentlemen, may I present for your appraisal, Ichthyothereol, or for the easier to pronounce name for the compound, (2S,3R)-2-[(1E)-1-Nonene-3,5,7-triyn-1-yl]tetrahydro-2H-pyran-3-ol

This, is found within tropical plants of the genus Ichthyothere, as well, I was surprised to find, within Dahlia species, D.coccinea for example is listed as containing this same compound. The Ichthyothere species, have a tribal use, by natives of the lower regions of the amazon basin, in that an insect, such as a grasshopper, is stuffed with the leaves, and rather differently from most traditional fish poisons, such as those based on natural rotenone sources like Derris spp. or on toxic saponins, which are strewn in the water, this is delivered as a poisoned bait.

The fish end up convulsing so violently that they jump out of the water, as they are said to do in massive agitation at the mere presence of this most virulent phytotoxicant in the water. It takes extremely low concentrations to cause violent convulsive poisoning in fish, which is fatal within minutes, after which, presumably, the natives scoop 'em out, gut them and take advantage of the vast sensitivity to tiny doses, delivered right to the fish, compared to eating the flesh of the fish, as ichthyothereol is also highly poisonous to human beings and other mammalian life, just as is cicutoxin and it's isomer oenanthetoxin, acting as GABAa antagonists, potentially ala picrotoxin as noncompetitive antagonists (not sure though, if like picrotoxin the polyyne alcohols bind preferentially to the GABA-bound conformation of the GABAa receptor when docking with the binding site.)

Either way, this would be precedent for a cyclic ring being incorporated into a polyyne GABAa antagonist convulsant poison of extreme virulence,

As far as structure-activity relationship constraints go, I can offer this much: upon doing some further reading upon the topic of polyyne alcohols with conjugated alkyne and olefinic bonds, it was originally believed, that the minimum requirement, was five, including the double bond, degrees of conjugation. This, apparently, whilst present in cicutoxin and oenanthetoxin, is not the minimum, it is believed now to be four degrees of conjugated unsaturated positions, which is the case in the structure of ichthyothereol, which has three internal triple bonds, a terminal methyl group terminus to the sidechain from the cyclic ring which is in conjugation with the present double bond, this being one carbon distant, separated by a C-C bond, to the hydroxyl group of the alcoholic functionality which lies within the pyran ring, and displays chirality, the location being one further C-C bond within the pyran ring, distal from the pyran oxygen bridge.
 
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