Opioids Methiodone/IC-26

[krkkhed]

Hello all. I've recently been gifted .4g of Methiodone/IC-26. RC Opioids are something I sorta have a love hate relationship with, as they all seem lackluster or just way too strong. I've tried 2-MeAP-237, Brorphine, Isotonitazene and probably another Zene or some fentanyl analogues (when I used to smoke fent). This one seems relatively new and a large amount of the info I've found about it is in German. I can semi-speak German so there is some info there I was able to gather, alongside other sources.

It seems it is active at 2-4mg, with some people using doses like 3.5-10mg for maintenance, but some say it doesn't produce effects until 150mg, some say 100, some say 50....It's kind of all over the place. Seems to take effect fully 2 hours after consuming it. Snorting it seems to not be worth it due to the powder being pretty caustic, other than oral being the main ROA some people have stood by boofing it. Many say it lacks the warmth and cozyness other opioids have but some people I've talked to disagree. Overall though I'd say it's more of a "maintenance" opioid. Makes sense I guess. Also apparently it builds up in the body like methadone does

- My first experience I didn't honestly feel all too much until the 4-5 hour mark, at which point I was very relaxed and slightly slightly warm in a way similar to methadone warmth. Didn't get a chance to check if my pupils constricted, I did have a slight itchiness as well. Was nice with hash. It took 2 hours for me to feel slight relaxation, then that was kinda how it was until 4-5 hours in, after which I stayed relaxed with a little warmth and then got tired as fuck, went to bed, and it was almost like a nod but not quite. Weird overall, I had taken a suboxone the day before and when I first dosed the Methiodone it hadn't been even 24 hours since the suboxone dose. Might've interfered a bit. I also tried snorting a bit on this day but it was so unpleasant that I ended up just capping the rest of the line and saving it for the next day.

- My second experience was the day after I had my first experience. The thought was "maybe it'll build up a bit from yesterdays dose and hit better". Was sort of the case, but that could also have been because I didn't take suboxone like the first time. It took around the same amount of time for it to really kick in, but yielded much more noticeable effects. It's about as euphoric as 2-Me-AP-237 (so a little less than something like Oxycodone), but has the sedation of Methadone. My pupils were constricted noticeably and my voice was very relaxed and sounded like I was on opioids (that growly/raspy voice that always comes out when I'm on opioids). I did go out drinking which definetely enhanced it's effects in terms of the sedation, but not much in the way of euphoria. I don't generally drink on opioids because it ruins the magic, but with this experience there wasn't too much "magic" there in the first place. When I woke up the next morning I was actually still nodding, but not with as much euphoria as before.

Overall my opinion of Methiodone is...it is certainly an opioid, but not a particularily recreational one. I could see this being great for maintenance, lasts long and doesn't really get you "high" so much as keep you well/keep you from craving other opioids. I'm sure that someone with lower tolerance could have some fun with this, but personally, it was only decent and nothing really special. Was fun to try it

I'm wondering if anyone else has tried this and what their experiences with it were like? I hope my report can yield some useful information. If anyone has any questions I would be happy to answer them to the best of my ability

 

[4DQSAR]

I checked out the papers on IC-26. It seems a single patent was issued and a single journal article in which the two enantiomers were resolved to check that like methadone, the (R) enantiomer is responsbile for opioid activity.

But since 1952 not a single person has written on examples of the 3,3-diphenylheptanone class of opioids in which the ethyl ketone is replaced by a sulfonylethyl.

What I find odd is that if they can produce something akin to methadone, they may as well made the analogues of heptazone or dipipanone. Two opioids related to methadone that are regarded as being much more abusable.

Maybe the makers followed the original patent and haven't worked out how to adapt it to replace the N,N-dimethyl moiety with a morpholine or piperidine ring? There are some methadone derivatives with truly hurculean potencies but, again, it would require some novel chemistry.

 

[krkkhed]

I checked out the papers on IC-26. It seems a single patent was issued and a single journal article in which the two enantiomers were resolved to check that like methadone, the (R) enantiomer is responsbile for opioid activity.

But since 1952 not a single person has written on examples of the 3,3-diphenylheptanone class of opioids in which the ethyl ketone is replaced by a sulfonylethyl.

What I find odd is that if they can produce something akin to methadone, they may as well made the analogues of heptazone or dipipanone. Two opioids related to methadone that are regarded as being much more abusable.

Maybe the makers followed the original patent and haven't worked out how to adapt it to replace the N,N-dimethyl moiety with a morpholine or piperidine ring? There are some methadone derivatives with truly hurculean potencies but, again, it would require some novel chemistry.

Interesting, thank you. I did read the article you mentioned in my research I'm pretty sure. Interesting, thank you.
It was not really a noteworthy or particularly unique RC opioid but it is certainly interesting to me, and that alone was worth it lol.

 

[notsmokeymcpot42088]

RC opi's have been largely dissapointing to me as well. Exception of u447780 (or w/e the first one was). I was lookin at this one too --- more as net for if they take/ I lose my sub script. Not deadly in the 10mg range and long duration sounds fairly appealing (To someone not seeking euphoria at least. (I wouldn't mind a little more than sub but I wouldn't cry about a little less either)

Only reason I can think they didn't go that way is legal or safety concerns. (but I am a laymens).

4dqdsar -- That is a shockingly small amount of data.

 

[4DQSAR]

4dqdsar -- That is a shockingly small amount of data.

Well, I'm not saying that's all there is, only that it's all I found.

I mean, maybe you can't alter that amine but it would be a good step in further exploring the QSAR to test if it it is a bioisostere of methadone.

I think someone even replaced the ketone with a phosophorous containing moiety and that was also active - but even less so.

What you can't do with either of those bioisosteres is to reduse the ketone to a secondary hydroxyl and esterifying said hydroxyl moiety. When you do that, you can obtain derivatives with extremely long durations of action (several days in some cases).

 

[krkkhed]

RC opi's have been largely dissapointing to me as well. Exception of u447780 (or w/e the first one was). I was lookin at this one too --- more as net for if they take/ I lose my sub script. Not deadly in the 10mg range and long duration sounds fairly appealing (To someone not seeking euphoria at least. (I wouldn't mind a little more than sub but I wouldn't cry about a little less either)

Only reason I can think they didn't go that way is legal or safety concerns. (but I am a laymens).

4dqdsar -- That is a shockingly small amount of data.

I never tried U47700 or 80 but I've heard very many things about them both good and bad. Caustic af supposedly like 2-Me-AP237 (fuck that shit)
This was a very subtle high, moreso than methadone but overall almost identical

 

[4DQSAR]

The odd thing is that the MOST potent of the U47 series has never turned up as an RC in spite of being some x23 M in potency.

Synthesis no more tricky BUT does require a custom precursor. I can only assume the cost of that custom precursor means that even when the product is several times more potent than the parent, it's not financially attractive.

 

[notsmokeymcpot42088]

I never tried U47700 or 80 but I've heard very many things about them both good and bad. Caustic af supposedly like 2-Me-AP237 (fuck that shit)
This was a very subtle high, moreso than methadone but overall almost identical

Oh caustic is definitely bad -- it was better euphoria wise than sub and a great deal cheaper. Glad I didnt run a whole ton of it or anything. yea things got a bit out of control for a year or two there forsure.

23x potency of morphine is not soo unreasonable compared to some compounds. Speculative question; where do you think said substance would land euphoria wise? Either way putting less of something caustic in seems preferable to me.

 

[4DQSAR]

Hard to say WHY a given opioid is euphoric while another is not. A few analogues of U47700 were made but I never sampled them. I mean, within that group did the 'euphoria' very? If not, I would presume this would be much the same. Maybe a slightly slower onset but not much in it as far as RO5 goes.

 

[notsmokeymcpot42088]

I do not know first hand because I only tried variation one of it -- but that got hit with a 'community ban' and I do remember people complaining that variation two sucked -- First one was like morphine this is like methadone or suboxone alot of statements like that. Right on, so potency is pretty predictable but euphoria is a bit more of a question mark I will take it. I read some speculation (very well may have been from you) in a different thread about what receptor is most responsible for euphoria, I'll look more into that. Im from the old days of mu1 = Grreaaatttt (tony the tiger voice) simply isnt the case.

 

[4DQSAR]

Well it's been demonstrated that there are several subtypes of MOR and it seems μ2 is most associated with euporia. But it's also most associated with repiratory collapse. But it appears that μ3 isn't well explored but appears only to be triggered by exogenous opioids and there may be splice varients.

Now I would GUESS it would most likely be similar to U4, but did you know that AH-7921 was made and tested before U-47700 but was rejected as being 'non euphoric'. Others sold it, we did not. We were quite keen on three things:

1-A compound must be safe
2-A compound must be legal
3-A compound must be euphoric.

We also made and threw away those Dianippon 1,2-diphenyl piperizine opioids on the basis that tests showed them to be boring.

In short, it can take quite a few experiments to find something good. But now people will put up with 'ok' if, as I increasingly see, people are taking stuff as 'ritual de la lo habitual' rather than as something to improve their lives.

 

[notsmokeymcpot42088]

Oh gosh good for you tossin the piperizine opi's those are scary and cold. Those are three solid rules. At this point I would be willing to accept something in the 'ok' category as I am dependent and you never know when a doctor is going to cut you off at the knees --- It would be nice to have somethin on the backburner for 'worst case scenarios' so to speak; I worry if I go full on for the most euphoric thing I can get --- may lead me in the wrong direction. I cannot pretend in the least to be objected to euphoria though; long duration with euphoria (and will power) should work just as well and be more pleasant.

I.E suboxone replacement programs are good but most prefer methadone (Hence no monthly supplies and stricter guidelines -- other than that I would say give me morphine replacement, well studied shorter w/ds more euphoria. SEEMS simple

 

[4DQSAR]

Yeah - AP-237 (Buccinazine) also seemed a bad idea ALTHOUGH I have previously noted that azaprocin is just a rigid analogue and that it's VERY likely that like azaprocin, the p-NO2 derivative will be some x2.5 more potent. But I judge still not much fun. Cheap, M potency, but not fun.

But there are still many scaffolds still to explore. In fact, I can bet what will replace fentanyl (if precursor control ever happens) but then all you have is something else like fentanyl...

 

[Soulfake]

Can anyone with deeper knowledge predict if the bioisosteric sulfur group will cause this molecule to not metabolize into that toxic methadone metabolite EDDP that can cause heart problems?

I tried a metabolite prediction software and it doesn't show any molecules with that n-ring https://biotransformer.ca/queries/168400/status?query_smiles=

I could imagine that such metabolites could further react to give that EDDP-like ring system: https://biotransformer.ca/compounds/ABMVNXCHBBJPHE-UHFFFAOYSA-N/image.svg

 

[4DQSAR]

Can anyone with deeper knowledge predict if the bioisosteric sulfur group will cause this molecule to not metabolize into that toxic methadone metabolite EDDP that can cause heart problems?

I tried a metabolite prediction software and it doesn't show any molecules with that n-ring https://biotransformer.ca/queries/168400/status?query_smiles=

I could imagine that such metabolites could further react to give that EDDP-like ring system: https://biotransformer.ca/compounds/ABMVNXCHBBJPHE-UHFFFAOYSA-N/image.svg

Is that double-bond side-chain simply an artifact of quickly drawing IC-26? Because I've not come across the compound as shown. But presuming it is just a mistake in drawing...

With methadone, it's the dinormethadone metabolite that is cardiotoxic. Now in the case of methadone, that toxicity is partly mitigated by the fact that the primary amine can react with the C=O of the ketone to form an imine. This is not possible with the ethylsulfonyl analogue. But then I don't think the metabolism of IC-26 has been studied so it's impossibe to know for sure.

Oh, and to be clear, it's the dinor metabolite of dextromethadone that is cardiotoxic. I posted a link in which researchers resolved the two enantiomers of IC-26 which demonstrated that as with methadone, it's the laevo enantiomers that are the actives (well, x20 more active than the dexto enantiomers).

Sci-Hub | The Resolution of Ethyl 1,1-Diphenyl-3-dimethylaminobutyl Sulfone. Journal of the American Chemical Society, 70(11), 3959–3960 | 10.1021/ja01191a532

Note that researchers were able to resolve the two enantiomers simply by using (d) tartaric acid to form the addition salt. Put simply, it doesn't appear that it takes much effort to resolve the enantiomers and while yes, you will end up with half as much product, that product will be twice as potent as the raecemic product.

It seems to me that making the ethylsulfonyl analogues of dipipanone, dipypanone (the pyrrole homologue) and phenadoxone would be much better targets for a few reasons. Those homologues have much faster onset times and significantly shorter durations of action but more impoortantly, are regarded as being much more euphoric AND do not have cardiotoxic metabolites. So purely on the grounds of safery I would go for one of those and not a bioisostere of methadone itself.