Opioids Etonitazene Analogues Megathread

[Wishdoctor79]

Hello. There's a lot of pontificating and posturing from people who seem maybe a bit jealous. I've been around the block and have every reason to believe the lady named isotonitazene and the lady named metonitazene are exactly what they say. Protonitazene I'm unsure and ditto for the flunitazene.

That said I was very cautious and transferred the powders to two plastic containers around the size of urinalysis pee-test containers, but the iso container was more robust and was approved for microwave heating. Just for safety, make it the best you got.

This isotonitazene is pure white and tiny uniform crystals it seems they took great care in processing.

The metonitazene can be eyeballed but don't try it with the isotonitazene. OK. Simple math, mods can check my arithmetic. 1 gram per liter is 1 milligram per milliliter. But if your sample is more than a gram it's too dangerous to divide it.

Much safer to dump the whole thing into distilled water wearing protection and outdoors if possible.

If your sample is ~5 grams the logical dilution requiring a minimum of exposure or loss would be a one-gallon container. Then you have ~1.2 mg/ml.

With a 1-ml insulin syringe it's possible to measure 0.1 ml. Do the math!

P. S. Wow I'm still high as the kites 12 hours after putting too many of those teeny tiny little white hygroscopic crystals on very tip of a sharp knife and touching to my tongue. No way I want an injectable solution around.

 

[Xorkoth]

Agreed that liquid measurement is the way to go. However I would make sure to have it be at least 20% ethanol to prevent microbial growth. I usually use vodka for my drug solutions, but you can use half vodka (assuming 40%) and half distilled water to give 20% alcohol. Without this, eventually microbes like bacteria will grow in there.

 

[Wishdoctor79]

Yes, I'm still at the oh wow, it really is real stage. Looking at my ordinary gallon jugs of distilled and wanting a better bottle with a screw lid, not press on.

Of course alcohol has a long history, can't hurt and can only help. Local conditions affect longevity and stability but of course it can't hurt and can only help. Unknown impurities are of course undesirable.

I say get the best container and splurge on two fifths of 195-proof Everclear!

P.S. I have confidence in my distilled and confidence in Everclear. Not so generic vodka. Go look up the specs. I've always used Everclear in all my potions and decoctions. Somehow using Sam's Club Vodka seems cheesy for a bottle with a million threshold doses. Scrimping for 20% likewise. If they don't have Everclear I'd have to buy five fifths of Stolichnaya. You only live once! And Godspeed to Mr. Putin.

 

[bingey]

Agreed that liquid measurement is the way to go. However I would make sure to have it be at least 20% ethanol to prevent microbial growth. I usually use vodka for my drug solutions, but you can use half vodka (assuming 40%) and half distilled water to give 20% alcohol. Without this, eventually microbes like bacteria will grow in there.

When I used to volumetrically dilute alphamethylfent , I used Benzyl alcohol as a preservative , the reason I went for this is that you just need 1% of the total volume of your solution if your gonna store it in the fridge and that unlike a significant concentration of ethanol it doesn't hurt the veins upon injection.



https://publications.aap.org/pediat...enzyl-Alcohol-as-Preservative-for-Intravenous

 

[Wishdoctor79]

I'm interested in learning of any kind of new understandings being developed to explain the "paradoxical" stimulating effects of daily methadone doses.

I use a combination of natural opiates and synthetics for my own daily maintenance program where they serve as tonics and vitamins in a regime that has nothing to do with getting high.

Isotonitazene may have some complementary actions as a tonic where my daily regime includes 1 ml BDO in water, TID, taken for it's GH effects. The two of them together seem to be exactly what my body needs.

 

[afent]

Anyone here got the orange batch of protonitazene? I had the brown last time and was good

 

[Fertile]

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I think this has been mentioned elsewhere but above is the most potent of the benzimidazole opioids. The NH in that chiral carboxamide side-chain overlays the NH in the unsubstituted piperidine ring of MCOPPBB i.e. it gives etonitazene significant NOP activity.

In the paper the compound is x6 more potent than etonitazene itself while having a slightly higher LD50 i.e. it's TI is >6 times larger than the lead compound. It was in a 1960s German paper that I spent a day translating and they evidently did use a training set (by hand!!!) to find the key moieties and their appropriate position and orientation. I suggest that they initially tried a -OH which when LogP was allowed for WAS more potent. They found which of the isomers it worked with and then tried various side-chains that allowed hydrogen-bonding.

It's worth noting that the phenol moiety of morphine can be swapped for a carboxamide and the result is a compound with only 1/2 of the potency (they discovered molecular overlap resulted in 2 isomers) but with significantly longer action. This fact has been used in the development of other opioids.

Just how potent the lead compound is has not been fully established although it's Ki at the MOP is 0.02. I suspect that the derivative I drew will not have a greater MOP affinity but it's duel MOP/NOP activity results in it being the more potent analgesic.
It's worth knowing the most potent compound in a series so you can build better training sets. I discovered what looked to be a MOP some x100 the potency of sufentanil but later research showed that it was also a duel MOP/NOP. The closest relative I've seen is in chapeter 8, page 298 of 'Opioid Analgesics, Chemistry and Receptors' by Casy et al. It is termed a 'spirane'. It's important to note that the N-CH3 of the amide moiety overlays the 4 position of the fentanyl class so a methoxymethyl (-CH2-O-CH3) or formate (-OC(O)CH3) HUGELY increases the potency.

In fact some of those spiranes have a MOP affinity <0.01 (one of them was 0.0034) i.e. it should be an order of magnitude more potent than etonitezine i.e. > x15000 morphine. Chemically quite complex, but if someone was to find a way of titrating it, 75 million doses (1 dose equalling 200 mg of morphine) would be about it.

I for one do not relish handling something more toxic than VX nerve agent. I mention this purely for educational purposes.

 

[izo]

I can only extrapolate from metodesnitazene, which was way too lame to even synth. I think these benzimidazoles are only worthwhile with a nitro group and a para alkoxy on the benzene ring. Then you get really potent opioids but I don’t know anything about the quality of the high.

 

[LucidSDreamr]

why people are creating these synthetic opioids?
How do they get into drug supply if its only ment to be a research chemical per say?

1) they are created by academics (professors at universities) studying SAR. They don't really care about anything other than publishing papers in scientific journals which is how they advance their careers and get funding. And discovery of new opioids is rationalized easily in the intro to the publication by simply saying you are advancing the understanding of opioids in the hope of one day creating non-addictive or non-dangerous treatments for pain

1a) Chinese commercial labs also keep creating new analouges to circumvent drug laws and continue to crush and embarrass the DEA at the drug war...which nobody in the public seems to be blaming the DEA at failing miserably at. Americans all think it's either Bidens or Trumps fault because Americans are stupid and too lazy to inform themselves on one of the biggest issues in society constantly killing their own children and fueling crime....they'd rather just hate and blame other people from other states instead because it's easier than reading

2) China labs sells them for profits and their government condones it to cripple American society.

If heroin was legal for registered addicts similar to how methadone is all of these dangerous RCs and the DEA would instantly become obsolete and the massive deaths, gangs, cartels, and drug related crime would disappear overnight

 

[Wishdoctor79]

Anyone here got the orange batch of protonitazene? I had the brown last time and was good.

I've compared from same source: isotonitazene, metonitazene, and protonitazene. Protonitazene looks very similar to metonitazene differing mostly in the color, with metonitazene closer to a brownish orange, the protonitazene having more red in the orange.

Distilled water for all: ~110 mcg in 0.1 ml.

Solubility of the isotonitazene in water isn't a problem but it could be difficult with this metonitazene and protonitazene. Benzyl alcohol helps them dissolve in water. 2% benzyl alcohol is about the maximum it can hold at room temperature.

I strongly recommend using benzyl alcohol as both a preservative and solvent. The orange and red powders don't easily dissolve in water. I added 1:200 elecronics-grade HCl for a pH of 2, approximating gastric juice.

 

[Samcl97]

How long does it take to become physically dependent on metonitazene? Is it the same as any other opioid?

 

[izo]

In the paper the compound is x6 more potent than etonitazene

can you give the reference?

 

[izo]

what i remember about different benzimidazole opioids:

metodesnitazene is absolute crap, you need 500mg for a really bad high. i think thats the case with all benzimidazoles without the nitro group, is determines this classes potentcy. (guessing).
etonitazene is allmost the most potent you can get out, methoxy is way weaker, still too potent to doesnt cause fatalities. isotonitazene sounded optimal (5mg) and 4-fluro substitution even with a nitro group was reported to be rubbish.
but im no expert on this class. maybe a second test substance from this class and ill look into it.

 

[izo]

can anybody get this article:

• DOI: 10.1016/j.neuropharm.2022.109263

 

[Fertile]

can you give the reference?

I drew it for you so you can easily work out the IUPAC name. I do not know if that is different in German. I only saw it in a small German language article from 1961 (if memory serves). It wasn't patented, you see, So I would have to search German language papers.

I noted that the N in the carboxamide moiety overlaid the N in the piperidine moiety of MCOPPB.

I believe it's the first time someone found a MOP/NOP ligand.

Janssen ALMOST stumbled upon one in 1964 but the modification that invoked NOP affinity reduced MOP affinity so it's analgesic potency was lower. That was the 8-benzyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one class of opioid.

 

[izo]

I drew it for you so you can easily work out the IUPAC name.

i knew you mentioned it before but where can i search for structure related papers/patens via SMILES?

 

[Fertile]

I normally use Pubchem but I checked there before posting. I THINK it was the same medicinal chemists who showed that the ethylsulfone & propylsulfone analogues of ketobemidine were as potent as the parent compound. I know I found both out on the same day.

Not a lot of help since neither of those show up in Pubchem either. But maybe it's easier to find that paper - then you have the names.

Sorry, but it's more than a decade ago since I looked at the papers and concluded that the increased synthetic complexity wouldn't make them practical targets.

I guess if people have found routes to etonitazine then swapping that N-diethyl with a piperidine or a morpholine (both in Pubchem) would be simple. While designing viminol, the Italian team did go through the dimethyl. I do not think the etonitazine designers tried chiral alkyl groups on the amine.

 

[izo]

I do not think the etonitazine designers tried chiral alkyl groups on the amine.

a fact on the side, the chemist that patented etonitazene in the 60ies in germany with a diploma stated his home adress in this patent. it is the town where i grew up, an am residing now again. in the 60s it must have had around around 15000 citizens.

 

[Fertile]

Sorry - I meant to say that the viminol designers went through the diETHYL.

If you can find the family address, he MAY still be alive. After all, I found Dan Lednicer was still alive (aged 86) and we were good friends for a couple of years. I still miss the guy. But the point is, these retired medicinal chemists will tell you ALL they did and are still sparky enough to pick up new ideas.

 

[izo]

The father of a friend is a retired chemist, wasn’t here when the apprentice came out. I ca ask him if he knows him.