• N&PD Moderators: Skorpio | thegreenhand

Phenylpiperidine Opioids - how low can you go?

The references in DOI 10.1007/s00894-010-0745-1 is the best starting point. It is something of a tree but if you use EPO links, you can step through them in a few hours. Janssen wrote extensively on the subject. ISBN-10: 1483119750 he details the divergence and development of several related scaffold with totally different activity. He built dreiding models (possibly the first in medicinal chemist in Europe to do so for commercial development) thus he was doing by hand what CHARMM does in software. One example that interested me was phenoperidine. While it's analgesic effects are well recognized, it was the anticholinergic activity that was perceived as the big advantage.
 
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Is there any info available about the activity of methyl, ethyl, etc. esters of tianeptine?

Also, the compound epimyrtine in the image below is found in some berries and fruits. A fentanyl or meperidine like derivative made from it would obviously be possible...

1-s2.0-S0278691512002591-gr4.jpg
 
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Still, for the likes of carfentanil, I just don't think 'cooks' have any business whatsoever fucking with it and it's ilk. Either making or having it imported as analogs. It's too potent, and just look at the trouble all the buggers fucking around slanging fent and the brothers and sisters of the group, is causing for legit pain patients and legit clandestine chemists and drug users.

I used to have a gear connect round here, homeless guy, altogether a decent lad who'd found himself in some unfortunate situation in life and lost his home. Then one time I went to pick up, he warned me about the gear, telling me it was the most potent shit he'd ever had in years, bought some, to find it monstrously potent, two weeks later, picked up another 11x20-wraps (10, one thrown in free). Same stuff, active, very very active when I'd place a quantity about half the size of a split lentil, or a bit less than a match head into my pipe and vaporize it. Rapid onset, very potent by weight, but shortish acting, 4 hours or so per pipe, and with a distinctly cold, clinical,bare feel to it, not warm and snuggly and euphoric like falling into a giant mound of cotton wool inhabited by a swarm of very horny, very naked, very perverted classically autistic girls and covered in maple syrup. Just...all business. An opioid that carries a briefcase, wears a suit, walks up, takes a billy club out of the case, smacks one round the back of the head hard enough to knock one out cold for 4-5 hours, places it back in the briefcase and fucks off.

After the second time buying, the homeless guy disappeared, despite my warning him to look elsewhere for his B, because this shit was dangerous, he just up and vacated, never to be seen again, never heard from him on the phone again, his dealers had vanished, their guys had gone, it was like a compact filovirus outbreak just stormed through a select group of people, extirpating them to a man. Didn't take long. A month after I first became aware of that batch doing the rounds, everyone was just...gone. I'm the only one out of them who I still know for sure to be alive (well, I'm making a fairly well educated guess there of course, but I reckon the rest of them are dead, due to the rapidity of disappearance coupled with the way not one of them could ever be reached again. And I'm pretty confident that *I* am alive, what with dead people not typically posting in neuroscience forums very much,)

With the LOWER potency fentanyls, fent itself, being capable of doing something like that, do we really, honestly NEED carfentanil doing the rounds? and stirring up no end of political slime into knee jerk idiotic reactions directed at handing down punitive backlash to pain patients who get prescriptions from doctors, and for the doctors themselves?
 
The pharmacologist in me says that carfentanil is probably better than fentanyl; check the half-life.

Obviously dilution has to be used. Carfentanil is already sold in the area I live in; even "high heat" is not even 1% w/w. Simple economics, people are quite happy to do "dope" that lasts ~8 hours rather than 2, blissfully ignorant of the actual dose of opioid.
 
Well yes, half life I'd agree.

Although IMO, the etorphines might be better, if one were to go for a superpotent opioid to manufacture. Certainly more INTERESTING from a consumer point of view. The fentanyl family are well known for their sterile, cold clinical nature, if that makes sense? At least there'd be a chance of the oripavine derivatives of that sort being more rewarding subjectively.

IIRC, etorphine is an epsilon OR agonist, what is known of this receptor? I know only relatively little about it. But etorphine and beta-endorphin are both agonist ligands here (buprenorphine being an EOR antagonist, apparently)
 
I think the advantage of fentanyl and its friends is that it's easily accessible by total synthesis. Etorphine and other morphinans need a source of the quadricyclic precursor somehow, be it thebaine, morphine, codeine etc.

Even things like racemorphan are less economical than fentanyl when you look at the complexity of synthesis. I'd imagine the hard part of carfentanyl synthesis is just making the 4-carboxy-4-amino-piperidine nucleus.
 
I think the advantage of fentanyl and its friends is that it's easily accessible by total synthesis. Etorphine and other morphinans need a source of the quadricyclic precursor somehow, be it thebaine, morphine, codeine etc.

Even things like racemorphan are less economical than fentanyl when you look at the complexity of synthesis. I'd imagine the hard part of carfentanyl synthesis is just making the 4-carboxy-4-amino-piperidine nucleus.

Carfentanyl is easily made with Ugi reaction, but like all fentanyls it is shit. Bentley compounds, oripavine derivatives are much more interesting, historically its a huge shame that Janssen demonized the oripavines for medicine in favor of fentanyl, Thats Business Bullshit, Belgian style.
 
Demonized? how so? and from my experience with a few of the fentanyls, I'd far sooner, if I were going to be doing any ultrapotent opioid, try one of the oripavines, etorphine, dihydroetorphine etc. than the likes of carfentanil.

Ugi reaction? never done one myself, but using it to make ultrapotent, unforgiving street-plague opioids....I bet THAT combination makes those chemists popular...

I've always thought fentanyl stinks=D
 
Carfentanyl is easily made with Ugi reaction, but like all fentanyls it is shit. Bentley compounds, oripavine derivatives are much more interesting, historically its a huge shame that Janssen demonized the oripavines for medicine in favor of fentanyl, Thats Business Bullshit, Belgian style.

well from a business standpoint,fentanyls are much cheaper produced,doesnt require natural precursors that often suffer shortages and/or weather factors.
Also less product per dosage means more $ per dosage profit(not per se but for fentanyl thats true).
Fentanyl has its use in breakthrough pain as a highly potent,very short and very fast acting opioid.
 
There appear to be ~12 hour types of potent opioid (~ 500m) with huge TIs that are only 2 steps from items of commerce. The problem for most people is acquiring the (quite legal) precursors. It's a puzzle of 2 parts; twice as many as drug producers need to solve and thus have no interest in solving. While F is the most profitable, F it will be. Michael L's prediction on opiates is coming true with the EU seeing pure, white, snortable H fetching €400/g compared to €70 for the most potent brown. I would expect the US market to resolve into the same model since the price and availability of pills is going crazy. How much would someone pay for a g of oxyM, for example? I'm sure I don't need to point out what a simple target THAT is. If you can make F that profits you $5/g or OxM that profits you $50/g then what are the smaller groups going to do?

Opiates can cause terrible damage to people but it just seems to me that people NOT dying and NOT losing everything in a matter of months provides a long-term market BUT Grisham's Law is played out in the opiate world more than in any other sphere of human endevour. Make the most money using the least effort over the shortest time span. Carfentanil is killing people in the UK - more than is commonly talked of. I've got enough coroner's court reports to convince me we need some HR in this field. an Irish company is developing drip-tests (drop from pin onto paper) that gives a really clear change from even tiny quantities so users can all be part of tracking the stuff.
 
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Demonized? how so? and from my experience with a few of the fentanyls, I'd far sooner, if I were going to be doing any ultrapotent opioid, try one of the oripavines, etorphine, dihydroetorphine etc. than the likes of carfentanil.

Do you know the back story? If you don't then this is a good read
http://www.cpdd.org/Media/Index/AwardSpeeches/LewisJ._Eddy1998.pdf

A common opinion amongst Macfarlan people was that Johnson and Johnson or Janssen Pharmaceutica had a major hand in getting Etorphine highly restricted under the UN single convention in 1961 leaving the medical market open for Janssens piece of shit drug fentany the timing fits their story.
 
Any guesses why fentanyls are not as euphoric as the fused-ring opioids? Maybe a bound fentanyl molecule dissociates from the mu receptor so slowly that the receptors become desensitized... Or then there are more subtypes of mu receptor than is currently known. Or you also need some amount of delta affinity to cause euphoria.
 
Any guesses why fentanyls are not as euphoric as the fused-ring opioids? Maybe a bound fentanyl molecule dissociates from the mu receptor so slowly that the receptors become desensitized... Or then there are more subtypes of mu receptor than is currently known. Or you also need some amount of delta affinity to cause euphoria.

I suspect it's selective μ activity is the cause. It does appear that both δ & NOP activity both play a role in the euphoria. NMDA antagonist and/or DRI/NRI action also elicit more euphoria. I've tried 3 opiate/NMDA antagonist analgesics and they most certainly are better. I've also had a light dose of an opiate/NMDA/DRI analgesic and that was pretty impressive. While it was only about as potent as M, 25mg was still VERY pleasurable.

You may well be right that the competitive action at the binding site is part of the subjective effect because I've not come across anything more than about x10 H that was as euphoric as H & nothing more potent that H that was also more euphoric than H. God knows the different number of allates of each receptor type and that shows up in things like AH-7921 that a few people like.... but that did nothing for me at all. U-47700 was good and I don't think I would touch anything much stronger unless in a medical format.
 
Back on the how low can you go - I see Krokodil is turning up in other countries. Now I can't see any species in the 'Expert Samples' to explain the terrible damage seen in users. I'm trying to find the AMATEUR samples. What is actually going into peoples veins? Kind of hard to work out a HR response when you don't know what you are responding to. Seems short-lived, seems highly euphoric and seems to have a huge dependence liability and being x10 M must make it a target to the 'meth cook' quality of work.

At once it's repellent and interesting. If their IS a simple way to remove the most hazardous species, seems like it WOULD be a good HR thing for people to know. Osteonecrosis & tissue necrosis surely cannot be due to the desomorphine itself since it WAS used medically. The bone-damage especially makes me wonder if the hypophosphite & hypophosphoric addition salts are the cause. It does show a frightening similarity to https://oem.bmj.com/content/oemed/19/2/83.full.pdf in which case would the addition of (3M) H2O2 to the 'cooker' instead of water oxidise H3PO2 & H3PO3 to H3PO4? Codeine phosphate can be administered parenterally (SC) with no issue. https://onlinelibrary.wiley.com/doi/pdf/10.1002/hup.2572 IF it's something that simple, it's eminently possible to vastly increase HR efficiency. The elevated levels of P does seem to cover the local and systemic toxicity.

I can't see a negative to the above. I don't think that with all of the existing media, people are going to make it their drug of choice and believe it's safe but for those living with the dependence, it might prove to reduce the chronic damage. http://sci-hub.tw/https://doi.org/10.1016/j.drugpo.2013.04.007

I fully expect to see the 'Nagai method' to become as infamous as the 'Seigfried Route' to F. (made famous by the DEA!) and in connection with the least able 'cooks' because as we have seen, several variations clearly explain the vastly different overall yield and ratio of desomorphine : 6-methyl desomorphine : 6-deoxymorphine-D : 3,6-dideoxydihydromorphine and unreacted codeine. Using the smell & colour to indicate completion of a reaction places it in the field of shoddy alchemy (sholcheny?).

As things stand, the yields are mostly VERY low, the toxicity HUGE and since it's being produced by the consumers (mostly), does not present a structured distribution network. I'm not going to dwell on the scope of possible reagents but safe to say that there are a lot. I believe the 'expert samples' show the results of different routes with 6-methyl desophine being a larger product than desomorphine in 2 routes but is totally absent in other routes. I presume that the CH3I from the O-demethylation of the phenolic group is involved and possibly the people have had enough knowledge to select a 'rate accelerant' and possibly Russian povidine-iodine is based on methanol.

'Poland, Czech Republic, France, Belgium,Sweden, Norway and other European countries with Russian immigration' taken from 'Kitchen chemistry: A scoping review of thed iversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions'... with the average morbidity rate of 35% per annum!
 
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Doesn't white phosphorus cause rotting of bones if enough of it accumulates in the body? If they use an iodine/red phosphorus method for reduction, it could be possible that some of the phosphorus converts to the other allotrope by some mechanism.

About molecules that contain the 4-piperidone or 4-piperidol nucleus, here's a plastic additive with brand name "Tinuvin 292".

hals-292.gif


I wonder how those methyls would affect the binding affinities of a meperidine-like compound made from the hydrolysis product of this...
 
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It does, it's known as 'phossy jaw', presenting as severe osteonecrosis of the jawbone, which essentially rots the jaw, causing it to degrade into a carious, pulpy, necrotic mass, which tunnels through to the surface, and ends up as a pus-oozing, foetid, stinking mass of rotting flesh and necrotic, suppurating, stinking slime.
This is AFAIK usually caused by prolonged exposure to the vapour via the inhalational route, with acute exposure, if the burns do not kill, causing all sorts of awful manifestations of its own.
I can't see red converting to white P in-vivo however. It takes strong heating in an inert atmosphere to turn red P into P4. Such as dry distillation in the absence of air, collecting the white phosphorus under ice cold water. AFAIK red phosphorus is pretty much nontoxic, to say nothing of insoluble.

If it could convert in-vivo then it'd be killing people, WP is similar in lethal dose to cyanide. Even tiny amounts can cause serious toxic sequelae via dermal exposure, such as temporary paralysis, severe muscle weakness and shaking, that lasts a long time from just a single small tissue burn due to WP.
 
Well it looks like PO2 3- & PO3 3- species are at least partly to blame. I can't help thinking that any loose P4 is dealt with based on reports on the syntheses. One of the links shows increased P but is that white/red/violet (black) P? Is that a PO2 3- or PO3 3-? Both of those are worse than RP (although I don't know about violet (black) P). While RP is obviously safe compared to WP, is it really safe to inject? By necessity the home-cooks have to use petrol or similar to extract the freebase C but I can only think that the expert samples HAVE been back-extracted. React, base, wash into DCM. Back-extract into hydrochloric acid (or other strong acid)...

It's VERY vague.

If 3 vol H2O2 will oxidise PO2 3- & PO3 3- to PO4 3- then perfect. It certainly oxidises P to PO4 3- so I'm guessing that it's via PO2 3- & PO3 3- species since it will have to dipropionate to HI at the same time.

It's of no value if it's too complex but IF something so simple works then surely it is valuable for HR purposes? Clearly users will put up with rotting for that hit so keeping them alive until we can put a programme together for them then... why not?
 
Even if one batch in 10 contains something really toxic like WP, it's going to cause a lot of damage...

The extraction of morphine-like alkaloids may not work in the same way as with amphetamines, as they are also soluble to alkaline solutions because of the phenol -OH, and it seems that morphine freebase is not soluble to petroleum ether (but is soluble to some other nonpolar solvents). Maybe it's some misunderstanding about how it should be purified by extraction.

Actually, looking at solubility data, codeine freebase isn't soluble in pet ether either, and I think that must have been the real reason why my own codeine extraction didn't do the trick as I expected...
 
Even if one batch in 10 contains something really toxic like WP, it's going to cause a lot of damage...

The extraction of morphine-like alkaloids may not work in the same way as with amphetamines, as they are also soluble to alkaline solutions because of the phenol -OH, and it seems that morphine freebase is not soluble to petroleum ether (but is soluble to some other nonpolar solvents). Maybe it's some misunderstanding about how it should be purified by extraction.

Actually, looking at solubility data, codeine freebase isn't soluble in pet ether either, and I think that must have been the real reason why my own codeine extraction didn't do the trick as I expected...


Codeine is so shitty it isnt even worth to be extracted,if i wanted to itch myself to death without a noticeable high theres better methods to do so
 
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