Hydrazones?

[Tony The Tiger]

This seemed like the right place to ask for some help identifying the possible nature of the following substances, which I believe fall into the category of "Hydrazone."

The lab in question claims they have anticonvulsant and relaxant properties, similar to benzodiazepines, but I am totally unsure as to the activity of these molecules. So any info on the effect they could have, a possible dose, and whether anyone has come into contact with these before would be much appreciated. I know the standard advice of start low and work your way up, but how low should I go before I escalate? 100 micrograms?

Thanks.

 

[FlippingTop]

does the 'lab' provide you with any pointers as to the dose?

 

[Tony The Tiger]

Nothing yet, I don't even know if it's legal in the UK?

 

[Privateer]

CAS Numbers:
Substance 1: 174790-56-8
Substance 2: 97742-10-4
Substance 3: is not registered

For Substance 1, one can find a report titled Structural modification of the primary amino group of anticonvulsant aryl semicarbazones which sounds promising enough, but the abstract was confusing to me: "The importance of the primary amino group in a series of compds. was detd. by replacing it with other substituents. The amino group was not essential for anticonvulsant activity. However, its replacement by an aryl ring generally abolished the activity, while a terminal phenylamino function was better tolerated." I'm not so sure if that means that the substituent pattern seen here increases or decreases anticonvulsant properties. To see what this is getting at, look at a semicarbazone structure and note where the primary amine is and then look at the structure of the molecules above and note how they are altered at that position. I believe the bolded part means that it is an ester, not the pattern seen in substance 1. I cannot say for sure because I cannot access the article.

For substance 1 one can also find an article entitled Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. In this article it is shown that substance 1 is effective at destabilizing microtubule formation in mitosis. See below.

Substance 2 is only described in articles about antibacterial compounds.

Substance 3 is not a registered compound and is not found in the literature.

What I found in the limited literature available is that anticonvulsant activity is suggested but not quite supported for members of this class, but it appears that Substance 1 can act in a similar way to colchicine in destabilizing microtubule formation in mitosis. This is bad and it can be classified as a poison if applied systemically.

Because of my findings, I would not recommend ingesting any of these compounds. They appear to be poisonous. If you're scientifically inclined, it might be handy if you could run a few in vitro zone of inhibition or apoptosis tests, though...

 

[Hyperthesis]

Uh yeah, good idea! All three suggested compounds will likely break down (chemically at the stochmach's acidic pH, as well as metabolically) to the corresponding acylhydrazides, which are in general very "healthy" stuff. Check the usual side-effects of eg. isoniazide. Further degradation releases hydrazine. Yay! To this add the exhilarant properties of primary anilines (yummi) and aromatic nitro compounds, ie. of substances 2 and 3 and their metabolites. In short, these compounds are most probably toxic and their alleged biological activity everything but proven, read: CRAP!

I know the standard advice of start low and work your way up, but how low should I go before I escalate? 100 micrograms?

Don't ingest them at all!

 

[ebola?]

Do not, DO NOT, purchase and ingest compounds on the basis of what "a lab" claims they will do.

ebola

 

[sekio]

http://public.carnet.hr/acphee/26312.pdf pg 268-271

these don't look like very promising drugs to be honest.

 

[Tony The Tiger]

Ok everyone, based on the information supplied here I will start at zero micrograms and stay there

I will leave this thread up in case they happen to hit the open market to avoid anyone making the same mistake I almost did.

Thanks!

 

[Tony The Tiger]

I sent this information to the lab, and they replied with what I think are the same structures drawn and written differently. Am I right in thinking these are just the same molecules? Or that they are similar and pose the same problems?

 

[Limpet_Chicken]

If these ARE GABAa ligands, and some are not mitotic spindle poisons, I still would NOT take them. No way in hell.

Some such hydrazines and hydrazones can be irreversible ligands, forming a covalent bond with the target. Examples of such hydrazines include phenelzine, the irreversible MAOI, and of the latter, oxymorphazone, a hydrazone derivative of oxymorphone, which again, binds covalently to the MOR.

Result in the latter case, is that it has an extremely long duration of action, until receptors are internalized, and new ones have to be inserted into the cell membrane. Effectively first activating, then nuking the receptors in question. With MORs, thats downright nasty, GABA receptors on the other hand...that could be highly dangerous, crispy-fry the majority of a poisoning victim's GABA receptors with a covalent ligand, and I'd imagine the resultant seizures/status epilepticus would be truly intractable, on an epic scale of ugly.

Bugger all chance of reversing an overdose with an antagonist too, seeing as how it wouldn't be possible to displace a covalently bound ligand using a drug having a tighter binding affinity. Using the simplistic 'lock and key' analogy of ligand/receptor binding, if the functional groups on either end don't protect against the hydrazone irreversibly binding, then somebody superglued the lock.

 

[ebola?]

Am I right in thinking these are just the same molecules?

You are mistaken. These all have different para-benzyl substitutions. You should examine the structures and see if there is anything different between them (and the latter molecule actually has a couple of differences from the first two, in particular, substitution of a thio group for a ketone and substitutions on both rings rather than just one (or rather, swapping ring nitrogenation for nitrogen dioxide bonded to a phenyl carbon)). Once again, if you know little or nothing about a compound outside of what a vendor tells you, do not take it.

With MORs, thats downright nasty, GABA receptors on the other hand...that could be highly dangerous, crispy-fry the majority of a poisoning victim's GABA receptors with a covalent ligand, and I'd imagine the resultant seizures/status epilepticus would be truly intractable, on an epic scale of ugly.

This is the shit of science fiction legend. XD

ebola

 

[Tony The Tiger]

You are mistaken. These all have different para-benzyl substitutions. You should examine the structures and see if there is anything different between them (and the latter molecule actually has a couple of differences from the first two, in particular, substitution of a thio group for a ketone and substitutions on both rings rather than just one (or rather, swapping ring nitrogenation for nitrogen dioxide bonded to a phenyl carbon)). Once again, if you know little or nothing about a compound outside of what a vendor tells you, do not take it.



This is the shit of science fiction legend. XD

ebola

I realised I was wrong when I got to work and had a closer look at the 6 substances next to each other. I just found it highly suspicious that I told them that the first 3 chems they had suggested were possibly toxic/poisonous, and all of a sudden there's another 3 which they have apparently made?! You are right in that I shouldn't mess with things I know nothing about, but then again, if I followed that rule I wouldn't even really be able to take paracetamol because I am pharmacologically retarded So I thought I would just ask on here because you guys seem to know your stuff.

Cheers for your advice Limpet Chicken, I will still stay clear.

Am I right in thinking that hydrazones/zines as a series are unlikely to yield anything in terms of desired recreational effects? They certainly seem to be very promising in terms of the treatment of diseases and various other ailments, or for that matter killing bacteria etc.

 

[Hammilton]

GABA receptors on the other hand...that could be highly dangerous, crispy-fry the majority of a poisoning victim's GABA receptors with a covalent ligand, and I'd imagine the resultant seizures/status epilepticus would be truly intractable, on an epic scale of ugly.

This is the shit of science fiction legend. XD

ebola

It wouldn't be that bad. The body would quickly re-regulate itself. fortunately we have many, many different sorts of GABA receptors- with more than a dozen possible combinations of subunits forming the GABA-A receptor alone. Unless it happened to be an antagonist at the actual agonist site (not one of the allosteric sites), which it doesn't look like it could possibly be, that wouldn't happen.

 

[Limpet_Chicken]

Hydrazines are fairly often pretty toxic, and in more than a handful of cases are irreversible ligands at their target.

Interesting trivia snippet of the day:

There are fungi that produce a toxin called gyromitrin, mostly found in the genus Gyromitra, the false morels, although other genera of ascomycete fungi do produce it. False morels are sometimes eaten, especially liked in finnland, where they are sold at marlet. False morels are in some cases quite large, usually brownish, brain-shaped mushrooms. Whilst eaten, they MUST be cooked extremely thoroughly. Boiled, the water thrown away, boiled again, the water tossed out, and only then can they be cooked, as the gyromitrin is volatile and thus is dissipated, whilst many mycologists certainly wouldn't eat it, and disagree as to weather it should ever be picked for the table, all agree that it must never,ever be consumed raw.

The toxin is a prodrug of monomethylhydrazine, otherwise known as rocket fuel. Literally.

The quantity of gyromitrin produced varies hugely, from area to area, season to season, and even per mushroom. Sometimes people have shared a meal of false morels, and some people have been just fine afterwards, whilst others eating from the same pot were poisoned, in some cases, nobody who ate the meal was poisoned, whilst the chef, who ate no mushroom, became intoxicated via the noxious fumes off-gassing from the cooking pot. IIRC there has even been a case of poisoning due to driving in a poorly ventilated car, carrying a cargo of false morels within.

Or, in people who do eat them without ill effect, they can do so for years, only to suddenly find it went and got them.

The mode of action of the poison gyromitrin (Acetaldehyde methylformylhydrazone) is due to metabolism into monomethylhydrazine, which forms a hydrazone with vitamin B6 in vivo, inactivating it, thus decreasing GABA synthesis. As well as being generally hepatotoxic, and also causing elevated levels of histamine to be produced.

Not a mushroom I would try myself, or recommend to others. Russian roulette in mycological form.
Very interesting toxicological profile though, what with a fungus of all things, producing rocket fuel.




Edit:

Not that bad ham? you have a good point there. It sure as Hades wouldn't be pleasant, though I'm sure.

 

[amanitadine]

I have enjoyed several species of Gyromitras countless times, including a few known to contain gyromitrin in varying degrees. It is highly volatile, and par boiling or even excessive pan frying has rendered them harmless in all of my experiences. They are absolutely delicious, but then again so is Amanita phalloides, or so they say. . .

Gyromitras are fun to pick as a few species follow the snow line up, and precede Morchellas by a few weeks. Good indicator species, good fun, and delicious. Oh, and "living on the edge bra"

I wasn't aware of oxymorphazone, wow covalent binding to the MOR. How perfect does that sound to half the dudes in OD? thanks for the info LC!