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Ketamine salts solubility

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someguyontheinternet said:
Do those exist?
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I've seen them available online and they're more expensive with them also being less common but I'm wondering if that might be due to people that use it to filter pills for example complain about it clogging like a valium would be best example of a pill clogging a micron filter lol.
 
Rectify said:
L.O.V.E_TRACTOR
1-(furan-2-yl)-2-aminopropane
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Think I had the methcathinone version of this and it was disgusting to vape and only lasted a few minutes. The furan seems to be too small for proper binding to the receptor pocket.
 
What is the benefit of a nasal spray? Midazolam does have the advantage of being one of the few 1,4-benzodiazepines that will readily form addition salts but oral bioavailability is very high and onset is already rather fast.

I did read that Mötley Crüe used to crush and mix Versed tablets with cocaine and referred to it as 'Zombie Powder' and while no experts in the matter, had a lot of shall we say 'hand's on' experience with a huge range of drugs. They apparently even managed to buy up all remaining US stocks of glutethimide to be consumed with Tylenol #4 - to hide their heroin dependence from family and friends.

I'm not saying it's impossible, I just don't see the point.
 
Ten steps?

Well if you got 80% yield on each step that would be about 10% overall yield. Since the figures for some steps is significantly lower, even 5% would be optimistic.

I'm also unclear that several steps are... well, single steps.

1-methoxy-4-[(1E)-2-nitroprop-1-en-1-yl]benzene to 1-methoxy-4-(1-methoxy-2-nitropropyl)benzene?

Surely one would make the nitro-alcohol (Henry reaction) and halogenate that? That's two steps less.

And reducing a nitroalkane when their is an unprotected carboxylic acid? I strongly suggest that's problematic.

Plus all examples have two chiral centres so in fact the synthesis as shown produces four enantiomers.

So of the specific compound 1.25-2.5% yield.

I'm reminded of 2-CT-13. Shulgin didn't really have to worry about yield because the object was just to build the QSAR but if memory serves the first couple of steps required 2000ml glassware and the last couple used 100ml glassware which gives some idea of the resources used. But don't forget he HAD already figured out the rest of the molecule - it was purely the 4-substituent he was working on. He had a logical reason to go for a difficult target.

Since it's essentially an alpha amino-acid derivative, I would be looking ad the syntheses of amino-acids. Since their is a definite practical use for the products, people have spent a lot of time working on novel syntheses. Methyl 3-amino-2-phenylbutanoate is in PubMed so clearly their is a paper on it's synthesis.

As for the piperidine derivatives. Well levophacetoperane demonstrates that reversing the ester works just as well (and I think cocaine analogues with the methyl ester reversed are also known and also seem to produce the same effects).

Over the years a few people have suggested that since methylphenidate and levophacetoperane are both active, phenyl(piperidin-2-yl)methanone might be a good (uncontrolled) target. The interesting thing I discovered was that Reaxys gives a reference and it turns out that the paper it references does not produce the product. It's a seemingly simple target that proves not to be simple.
 
I have made nasal spray before you get distilled water or depending on the chemical a different solvent midazolam happens to be one of the only benzos water soluable, the rest are soluable in PG or ethanol but also many other reasons for nasal sprays cocaine, but even better are the super potent benzomidozoles opiates. But atleast motley crew used versed in their zombie dust bc it was actually sortable being water soluable just make sure you have your volumetric dosing down and you should be good can get nasal sprayers on amazon. Good use is for the new ultra potent benzomidozole opiates and benzo/theinos derivatives. Just know mosy benzos are NOT water soluable
 
AlsoTapered said:
What is the benefit of a nasal spray? Midazolam does have the advantage of being one of the few 1,4-benzodiazepines that will readily form addition salts but oral bioavailability is very high and onset is already rather fast.

I did read that Mötley Crüe used to crush and mix Versed tablets with cocaine and referred to it as 'Zombie Powder' and while no experts in the matter, had a lot of shall we say 'hand's on' experience with a huge range of drugs. They apparently even managed to buy up all remaining US stocks of glutethimide to be consumed with Tylenol #4 - to hide their heroin dependence from family and friends.

I'm not saying it's impossible, I just don't see the point.
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I don't see why my reasons are necessary to help me with this but I'll let you know 1 reason I want this on hand and that's for a bad shroom trip I guess but idk if an antipsychotic of some sort might do a better job at "killing a trip" so to speak but I guesss if I don't use it for that it can't hurt to have a benzo that'll work in literally 2-7 minutes instead of like a minimum of 15-30 minutes from oral use.
 
Echotango said:
I don't see why my reasons are necessary to help me with this but I'll let you know 1 reason I want this on hand and that's for a bad shroom trip I guess but idk if an antipsychotic of some sort might do a better job at "killing a trip" so to speak but I guesss if I don't use it for that it can't hurt to have a benzo that'll work in literally 2-7 minutes instead of like a minimum of 15-30 minutes from oral use.
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Their are quite a few studies on sublingual and buccal administration of benzodiazepines with the papers available on-line. The conclusion was that onset and bioavailability was almost identical to IV administration. Neither are instant which I suggest is because the drug has to cross the BBB and it's that which is the limiting factor.

They are the first to point out that it's an off-label ROA BUT at least it ensures that until administration, the drug is being stored in an approved format. Solutions (e.g. injectable formulations) generally require careful formulation and almost always have a much shorter shelf-life. I don't think they become dangerous, I just think that N-oxides (for example) form which slowly reduces the amount of active.

I mean, if it psychologically makes you feel better to have a nasal spray then by all means, but it seems like a lot of research is already out there and if sublingual essentially achieves the same goal, it requires no action. You just have to remember to hold them under your tongue.
 
AlsoTapered said:
Their are quite a few studies on sublingual and buccal administration of benzodiazepines with the papers available on-line. The conclusion was that onset and bioavailability was almost identical to IV administration. Neither are instant which I suggest is because the drug has to cross the BBB and it's that which is the limiting factor.

They are the first to point out that it's an off-label ROA BUT at least it ensures that until administration, the drug is being stored in an approved format. Solutions (e.g. injectable formulations) generally require careful formulation and almost always have a much shorter shelf-life. I don't think they become dangerous, I just think that N-oxides (for example) form which slowly reduces the amount of active.

I mean, if it psychologically makes you feel better to have a nasal spray then by all means, but it seems like a lot of research is already out there and if sublingual essentially achieves the same goal, it requires no action. You just have to remember to hold them under your tongue.
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Lol using Midazolam sublingual has similar issues as trying to use the tablets for nasal just bit less annoying as it has a lot of binders and fillers and doesn't taste good I'd imagine either... I just hope it doesn't taste awful like some benzodiazepines.

I also find using benzos in a solution sublingually instead of via a crushed pill into a powder then dumped under the tongue does appear to absorb quicker and more thoroughly but that might just be placebo on me lol idk... it makes sense though.


Also the studies for sublingual aren't a good ROA for every single benzo are you sure Midzoalm is 1 of them? I'd assume it is based on the fact it's suitable for nasal administration.


If Midazolam is a benzo suitable for sublingual ROA where do I find out 100% for sure the potenital absorbption % for sublingual ROA of Midazolam which I'll make a solution out of the pills for that? Actually I just remembered that Midazolam DOES have a lower oral bioavailability but I'm not sure the difference of the sublingual vs. intranasal bioavailaiblity % but if someone with knowledge on that subject can figure it out.

Midazolam is a bit weird in terms of ROA absorption % etc. compared to most other RX benzos these days I to make a cocaine nasal spray since I have some lying around and I've always wanted to make it for various reasons like less damage to the nostrils and more effective absorption potentially but my concern has always been on how do I correctly and acccurately measure the dose per spray even if I know exactly how pure it is? its roughly 84%. What information do I need to help determine the dose per spray of liquid with I'm assuming PURIFIed and not distilled water will work and i don't need any additional solvent for cocaine as I know it's super water soluble.
 
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Sublingual plus oral midazolam without intravenous access to complement topical anesthesia for phacoemulsification surgery

OA Text is an independent open-access scientific publisher showcases innovative research and ideas aimed at improving health by linking research and practice to the benefit of society.
oatext.com oatext.com

Premedication with midazolam is equally effective via the sublingual and intravenous route of administration

Signa Vitae is an international peer-reviewed open access journal, which is currently indexed in SCIE, scopus, etc. It covers many aspects of adult, pediatric and neonatal intensive care, anesthesia and emergency medicine
www.signavitae.com www.signavitae.com

Yep - I just posted the first three mentioning midazolam but their are MANY. The key finding that sublingual was as effective as IV. Midazolam is particularly water-soluble (for a benzodiazepine) and so is the most suited to sublingual administration but the methodology has been applied to most of the more water-soluble examples.
 
AlsoTapered said:

Sublingual plus oral midazolam without intravenous access to complement topical anesthesia for phacoemulsification surgery

OA Text is an independent open-access scientific publisher showcases innovative research and ideas aimed at improving health by linking research and practice to the benefit of society.
oatext.com oatext.com

Premedication with midazolam is equally effective via the sublingual and intravenous route of administration

Signa Vitae is an international peer-reviewed open access journal, which is currently indexed in SCIE, scopus, etc. It covers many aspects of adult, pediatric and neonatal intensive care, anesthesia and emergency medicine
www.signavitae.com www.signavitae.com

Yep - I just posted the first three mentioning midazolam but their are MANY. The key finding that sublingual was as effective as IV. Midazolam is particularly water-soluble (for a benzodiazepine) and so is the most suited to sublingual administration but the methodology has been applied to most of the more water-soluble examples.
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Okay thanks for the information. Now I'll definitely use sublingual route instead if it is indeed truly the same as I.V. or at least better absorption than a nasal spray. But I read conflicting information so I'm not sure what source of information to trust for a "verified" amount of absorption?
 
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Long experience has taught me that any compound that takes more than four (efficient steps) to produce either requires a special production-line (if a lot is needed) or costs an absolute fortune (look at butorphanol - $284000/Kg even after 40 years of development.

I mean, a LOT of compounds listed are ALREADY listed as building-blocks with PubMed offering suppliers - but just ask for the price for a gram.

I was quoted $15000/g for 3,4-dihydro-2H-spiro[naphthalene-1,4'-piperidine] - and that's just an intermediate.

What you are paying for is someone who can has invested millions on equipment & who can reliably produce a stated compound for maybe $12000/Kg - that might seem a high profit margin but sometimes their theoretical route doesn't work and they make a loss. BUT you pay the quoted price.

Try getting a quote for something you have drawn that is already in PubMed. It will be thousands per gram - and that's people who have spent decades working in the field of supplying building-blocks.

Unless it's something active (and who knows since no rationale is given) and indeed HIGHLY active then it isn't going to happen.

Believe me, Chinese labs are not above just sending something else so you need instrumentation data and, obviously, the ability to read it.
 
Yeah - it's still 14 steps (if memory serves). Of course, cleaver chemists will use retrosynthetic strategy and MIGHT find a more efficient synthesis from some more common compound.

But I've been looking for 26 years. Nothing yet. But sooner or later one of the hundreds of intermediates I check on a weekly basis will suddenly become cheap. Most of drug design it just THAT mundane.
 
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Library Genesis

libgen.li libgen.li

Above is the original paper discussing the extreme potency of BDPC. What is so fascinating is that Lednicer et al. were able to construct a Dreiding model which shows that the compound can perfectly overlay fentanyl.

'The two benzene rings can be directly superimposed (though the link to the rest of the molecule is rotated by 60'). The basic nitrogen atoms of the two molecules similarly fall in the exact same spot in space as do the extreme right-hand benzene rings. The hydroxyl
group in 1 falls in the middle of the amide function of fentanyl.'

I think this especially useful for students who struggle to visualize a chemical in 3D. When drawn in 2D two compounds may look entirely unrelated but in fact, overlay perfectly in 3D.

Other examples of this are U-47700 perfectly overlaying prodine or 4-phenyl phenapromide perfectly overlying fentanyl. I can extend this to other classes but I've stuck to the class of compound of with I am (fairly) certain of the 'salient features;.
 
BTW it's the acetyl ester derivative of Spirodone that has that huge activity and long duration. By acetyl ester I mean the ketone is reduced to a secondary alcohol and esterified. That adds a chiral centre and only one enantiomer is very active.

I honestly believe it should be studied as a treatment for people who become dependent on crazy strong opioids like carfentanil because methadone wouldn't work - too toxic. But a compound some x212 morphine (i.e. over 400 times as potent as methadone) with a duration of action of three days. That seems potentially useful.
 
^ Too bad you can't patent it.. you'd make million$ for sure. I found those Janssen compounds quite interesting!
 
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