Ketamine salts solubility

[emkee_reinvented]

My garden, with those will-less plant's in it. That I can feed LAVA starch it contains all nutrient's needed for good mineral rich ground. As they don't complain you can even cover the leaves with the ash. And by nature's design its slow release. Not for human consumption the plant's will be.

But that or LAVA the body builder supplement won't remove Lipofuscin. Which is the reason for creating a thread about Centrophenoxine. To see if the claimes are still standing.

 

[AlsoTapered]

Lave is an amazing thing. The Romans produced a form of concrete using it and two thousand years later, it's still as strong as ever. It's BETTER than modern concrete.

More importantly, it doesn't require the dehydration of calcium carbonate to produce it and modern concrete production is responsible for 10% of the world's CO2 production. I cannot help thinking that at least in nations that have locally sources, they could use it and have better results at a lower cost both financially and to the environment.

 

[G_Chem]

I'm prescribed this as of recently, for bipolar/schizoaffective disorder, I'm kinda scared of it because I don't want to experience opioid withdrawal, but the fact that it looks like a chef with a moustache mixing a margarita is calming my nerves a bit, thanks for showing me what the molecule looks like!

Definitely report back on how it makes you feel!

-GC

 

[emkee_reinvented]

Lave is an amazing thing. The Romans produced a form of concrete using it and two thousand years later, it's still as strong as ever. It's BETTER than modern concrete.

More importantly, it doesn't require the dehydration of calcium carbonate to produce it and modern concrete production is responsible for 10% of the world's CO2 production. I cannot help thinking that at least in nations that have locally sources, they could use it and have better results at a lower cost both financially and to the environment.

Is this also why Venetia which is build in water still stand, bit off topic. There concrete is so good itt beats ours today. They had an investigation on how they made it. I bet Lava could have been involved.
Even normal old conrete is better then that prefab shit of today. Look at the Atlantic wall the German's build or ancient monumental concrete building in harbour's of Rotterdam.

Centrophenoxine vs. the dr's med's is like lava to artificial fertilizer containing only N-P-K.

 

[Soulfake]

I guess the cheapest synthesis would decide how the enantiomeric ratio would be, as far as I know the enantiomeric ratio of desmethyl-tramadol is quite variable depending on route and reaction factors, I once had some odT fumarate which lacks almost all noradrenergic effects (almost no euphoria and only relative boring sedative effects), while some charges almost only have those and gave you too much noradrenaline. If there is no enantiomer-selective synthesis that is cheap enough, one would probably use normal odT as starting material for esterification with the pregabalin (although pregabalin is usually used as only one enantiomer if I remember correctly, what would that mean for those frankenstein molecules?)

I wonder how pricey such compounds would be, basically it should be the cost of both compounds plus the esterification, which shouldn't be too complicated I guess. But I'm really just a layman, most things I "know" about chemistry stem from pattern recognition by looking and reading about molecules, pharmacology etc. for about 15 years ^^', and a bit of luck mixed with alchemy for the necessary whimsicality as a crazy drug nerd.

edit: you can also find the complete Marvin Suite somewhere to download, you can make chemical overlays with it and much more. A few years ago you could download it on the makers website when registering as a student or something similar, but now it seems not as easy to find. If someone finds a legal download link pls share

Marvin

Draw with Marvin, import, edit, and export your chemical structures effortlessly from one simple application.

chemaxon.com

 

[AlsoTapered]

I believe tramadol (as it's presented as a medicine) consists of the trans-pair but in actual fact if the (1S,2S) enantiomer were isolated, it would be a more potent opioid and importantly, a much safer one. I believe traces of the cis-pair are found in medicinal forms in trace amounts but are more or less inactive.

If you are considering a compound that is 2:1 pregabalin: tramadol then it's worth asking if you will accept the trans-pair so in effect, hydrolysis produces 3 different actives OR you choose to go the extra mile and specify the (1S,2S).

I'm sure you know that replacing the tertiary hydroxyl of (1S,2S) tramadol with a fluorine, the compound is some four times more potent (as opioid) than the trans-pair of tramadol i.e. 8 times more potent than the (1S,2S).

OK, it's a tricky reaction - fluorination of tertiary hydroxyls requires DAST or other hazardous reagents but you do end up with something that's about as potent as morphine.

 

[Soulfake]

Yes I thought about a halogenated version but I wonder why it hasn't been considered by the big RC industry yet? Is desmethyl-Tramadol in general somewhat tricky or pricey to synthesize? Otherwise I see no reason why there haven't been many analogues already popping up.

But somehow I'm not a big fan of halogenated compounds anyways, besides benzodiazepines. Maybe because of my experiences with synthetic cannabinoids, if you smoke so many different compounds you somehow get a "feeling" for what makes fluorinated noids different in general, not that it's feeling or being more toxic or so, I can't find words for what I want to say. Maybe it has to do with the western pharmaceutical system where everything gets halogenated so you can sell 1/100 the amount and quadruple the profit, just like we have seen with synthetic noids. The more potent the better and mainly because of economics, I wonder how many good compounds there are out there that maybe need bigger doses, don't have the narrowest possible effect spectrum etc. to be patentable but would help much more with less side effects as an addition to the medicine spectrum.

I'm always fascinated by the russian pharma industry during sovjet times, even though they didn't have better or as-good medicine at all, there are so many interesting compounds and general ways of looking on how to make medicine, from the natural extracts like Schizandra, Eleuthero and Rhodiola to compounds like Phenibut or Picamilon, the racetams like Phenylpiracetam or Noopept and the peptide compounds like Semax of which there have been thousands being researched. Maybe sometimes it doesn't need a high potent patentable compound when glueing niacine and gaba together is enough to get a cheap and effective medicine for mild conditions with no side effects. A bit like a bridge between natural and chemical therapy.

But I'm getting off topic here...


If the first compound would convert into clonazepam inside the body by ring-closure, would the second compound create Meclonazepam (not Methylclonazepam)? I loved that stuff, favorite benzo after Etizolam.

How dangerous do you think are those benzophenone-prodrugs? For me as a layman they look a bit suspect with those two benzol rings, but it seems like a great way to play around with many new prodrugs. Established ones like pro-Diazepam are known to be safe even when injected into the muscle or blood, and from what I found in literature others like Alpra-Triazolobenzophenone shouldn't be very toxic, but for example I couldn't find one that uses the nitro unit in such a pro-drug, or the pyridine ring like Bromazepam and Pyrazolam. Could those impart toxic properties, or haven't they been considered because of lower effect possibility, worse perfomance, etc.?

 

[AlsoTapered]

The former will ring-close depending on pH BUT the problem with such prodrugs is that the amine from one molecule could dehydrate with the ketone of another to form a dimer unless the material is diluted to reduce the chances of that to a vanishingly small level. Now the later needs a bit more of a push to dehydrate - or at least I know that making 3-methyl benzodiazepines seems to require rather more vigorous consitions.

But surely the feature that should cause most concern is the aromatic nitro? @fastandbulbous helpfully posted a paper in which it was shown that nitrobenzodiazepines produce two toxic metabolites. Not dangerous under normal dosing conditions but in overdose they were fare less forgiving. I think one metabolite is hepatotoxic, I forger the other.

That's why intentional overdoses of diazepam (at least consumed without other drugs) is rarely if ever fatal but with nitrazepam and flunitrazepam, it's a known issue. Nitrobenzodiazepines, if discovered today, likely wouldn't get an ML.

 

[izo]

Is desmethyl-Tramadol in general somewhat tricky or pricey to synthesize?

it is one step from commercially available tramadol. yield is in the high 90ies i think so rather cheap to make.

 

[AlsoTapered]

You now need an appropriate licence to purchase tramadol on the open market. It IS an incredibly cheap precursor and indeed, it's very simple to perform the O-demethylation. But don't forget - tramadol has 4 enantiomers. I'm PRESUMING that the trans-pair is what is being sold.

A quick gander at US5733936A reveals that tramadol analogues are a more complex subject than is generally known. But it's important to begin with the original patent. US 3652589. Note the low TI (2.1).

I guess that if one could find better way to replace that tertiary hydroxyl moiety with a fluorine, THEN you would have a very attractive RC.

Now, resolving the (1R,2R) and (1S,2S) is a bit clunky but I would be prepared to bet that somewhere a patent will present a good route. Third party researchers might reasonably gamble that one day the (1S,2S) enantiomer might have become a new product and finding and patenting the OPTIMAL resolution would then be of value - said third party could charge manufacturers to use their methodology. It's actually common. Pick a medicine that is marketed as a raecemate and search the patents...

That's why I always tell people to sit and read patents. Often their is no 'novel' chemistry involved. Somebody somewhere will spot a possible profit.

BTW while rat tail-withdrawal tests are of limited value, it's worth noting that:

Tramadol - ed50 15.40 mg/kg
example 18 O-DMT - ed50 5.64 mg/kg
example 2 (1S,2S) O-DMFT 0.64mg/kg

Now, while I cannot go into detail, I would at the very least find a way to separate the Tramadol trans-pair so O-demethylation would yield (1S,2S) O-DMT which won't only be twice as potent but also subjectively better.

But best of all would be to separate trans-pair, exchange -OH for -F and then O-demethylate.

Of course, I can't explain HOW someone would go about doing that but the figures don't lie and although those tail-withdrawal tests when used to demonstrate the potency of morphine vary hugely BUT I believe it's essentially around the same potency as M and without the SNDRI activity, a lot safer than O-DMT.

EDIT EP0787715A1 resolves tramadol.

 

[Rectify]

It Feels Like I'm On

METHODRONE
1-(4-methoxyphenyl)-2-methylamino-1-oxopropane

There Are 15 Dead People For Every 1 Living One.

 

[Rectify]

SINGLE_INGLE
1-(4-methoxyphenyl)-2-ethylaminocyclohexane

IZO_IZOD
1-(3,4-methylenedioxyphenyl)-2-dimethylaminocyclohexane

AMPLE_SAMPLE
2-phenyl-1-aminocyclohexane

 

[Rectify]

]

PARTHENOGENESIS
1-(1-piperidinyl)-2-(4-bromophenyl)-cyclohexane

BIG_BLACK_NEMESIS
1-(3,4-dichlorophenyl)-2-methylaminocyclohexane

BRAND_NEW_SEGA_GENESIS
1-phenyl-2-methylaminocyclohexane

 

[Rectify]

JIMMY_JOHN'S
1-phenyl-2-(1-pyrrolidinyl)-cyclohexane

SUBWAY
1-(4-methoxyphenyl)-2-(1-pyrrolidinyl)-cyclohexane

PIZZA_HUT
1-(3,4-methylenedioxyphenyl)-2-(1-pyrrolidinyl)-cyclohexane

PUBLIX
1-(3,4-methylenedioxy-5-methoxyphenyl)-2-(1-pyrrolidinyl)-cyclohexane

KROGER
1-(3,4,5-trimethoxyphenyl)-2-(1-pyrrolidinyl)-cyclohexane

 

[Rectify]

[

ROSE_PETAL_AMINE [RPA]
1-(3-amino-but-1-ene-1-yl)-(2,2,6-trimethylcyclohexene)

from B-IONONE
$$$

Would A Rose Petal Amine By Any Other Name Smell & Taste The Same?

RPA Entered The Patent Chemical Literature In March 2005 As An Intermediate To A Purported Antimicrobial.
NC(C=CC=1C(CCCC1C)(C)C)C

 

[Soulfake]

Would the pure 1S,2S-oDMT really be better? We have a batch of fumarate going around in Germany and it feels like oDMT but without all of the adrenergic goodness and most people are disappointed by it, so I guess it has more of the opioid-isomer than the NDRI. It keeps the withdrawal away and in high doses you feel nice, but this special euphoria is missing that makes oDMT so great. It really feels like you need that noradrenaline to have this "relaxing stimulation" flowing through your body and get this motivational mindset, if this fumarate has really more of the opioid-isomer than I wouldn't prever this over the adenergic one. In the best case you could order both isomers pure and mix them how you like.

This adrenergic stim effect is also what seperates oDMT from most other drugs, only Tilidine with it's DRI effect would be comparable. Wait, Tilidine....I have to go to the drawing board ^^

I wonder about the structural relationships between Tilidine and Tramadol (I know there are many others with a comparable spectrum like Pethidine, but that would get too much if it's not needed for explanation).

What influence does this OH- or carboxyethylchain on the cyclohexylring have? I know it simulates a part of the morphine base, but why does for example Tilidine have no hydroxyl on the phenyl? If you search for Tilidine-like analogues and estimations of targets and potency at thiat swiss website, you get almost nothing.

What influence does the hydroxyl on the third position of the phenyl ring have for those opioids and why doesn't Tilidine need one, even though it seems to simulate the morphine base like most other of those simplified molecules?

And why does Tilidine use a cyclohexene ring instead of cyclohexane? (I also wondered this for Tetrazepam which is the only benzo with cyclohexene)

(If anyone has access to the original research papers for Tilidine where everything is explained in detail I would be very thankful!).

 

[AlsoTapered]

Adding a m-phenol to an opioid isn't a magic trick to increase activity and esterification is only of value if the ligand orientates itself in a manner so that a H-bond acceptor will increase affinity.

Nortilidine is the active drug - tilidine is a prodrug. The researchers tried adding a m-phenol to tilidine and the result was inactive.

Don't imagine chemicals as flat 2D objects - they are 3D objects which I have mentioned So each of the above could represent one of four different 3D structures. In the case of tilidine and nortilidine, only one of the four enantiomers has opioid activity.

Tramadol is unusual with the (1R,2R) being an SNDRI and the (1S,2S), or more specifically the O-desmethyl metabolite having MOR affinity.

One of the important thinks to know is that nobody has yet managed to predict if a given compound WILL be an opioid. When you read the story about every single one of them was discovered by accident. Certainly even when teams searched for new opioids, they would look through previous work to find compounds with at least SOME analgesic activity and then use rational design, high-throughput screening or in-silico modelling (depending on the era of drug discovery).

The fumarate salt is generally used in sustained-release formulations BUT I would have guessed that O-DMT would come in the form of it's hydrobromide salt since HBr is the reagent used to perform the O-demethylation. Something odd going on there. But then, how do you know what you really have?

IF I were in Germany, I would have a Chinese lab make example 2 from the patent. It isn't explicitly controlled anywhere as far as I can tell.

 

[Rectify]

WOKE
1-benzyl-pyrrolidine

EWOK
1-piperonyl-pyrrolidine

 

[Rectify]

NACHO
1-amino-2-phenylcyclopentane

MAMA'S
1-oxo-3-(3,4-methylenedioxyphenyl)-4-ethylaminocyclopentane

IMMA_B_TRIPPIN
1-amino-2-(2,5-dimethoxy-4-bromophenyl)-cyclopentane

MAE_BE_SO
1-(4-trifluoromethyl-3,5-dimethoxyphenyl)-2-aminopropane

MAE_B_NOT
1-(3,5-dimethoxy-4-nitrophenyl)-2-aminoethane

 

[Rectify]

PLAYBOY
1-oxo-3-methylamino-4-phenylcyclopentane

PENTHOUSE
3-methylamino-4-phenylcyclopentane

CLUB
3-methylamino-4-(3,4-methylenedioxyphenyl)-cyclopentane

OUI
1-oxo-3-methylamino-4-(3,4-methylenedioxyphenyl)-cyclopentane

HO-CH2CH2CH2CH2-OH

HUSTLER
2 ethyl alcohols stuck together backwards
1,4-butanediol