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IRREVERSIBLE OPOID AGONISTS - Hydrazine and azine opiate derivatives

- Fri, 06 Jul 2018 03:58:39 EST pv6fN59z No.79161
File: 1530863919876.png -(5901B / 5.76KB, 220x159) Thumbnail displayed, click image for full size. IRREVERSIBLE OPOID AGONISTS - Hydrazine and azine opiate derivatives
Hey guys.

So recently I've been interested in irreversible opiates.

A couple decades ago some scientists were able to do this by adding a hydrazine at the 6 ketone of oxymorphone, as well as at naltrexone/naloxone, making oxymorphazone and the corresponding nalts.

When tested, these hydrazines lasted extremely long, and blocked any further effect of opiates in animals. As well, radioactive versions of the drugs cold simply not be washed away from tissue expressing opiate receptors. Meaning these drugs were staying bound to the receptor.

Originally it was thought that oxymorphazone itself was doing the irreversible binding, but it was later determined that the oxymorphazone was joining up with itself spontaneously in solution, creating a dimer of sorts, oxymorphazine.


There's no wiki on Oxymorphazine, but here's something similar: https://en.wikipedia.org/wiki/Oxymorphone-3-methoxynaltrexonazine

It's just two oxymorphones joined by a hydrazine at the 6 position of each.

It was found that the hydrazine derivatives would spontaneously form the azine in solution, especially if it was acidic. The azines were the real irreversible agonists.

Here's a paper on it: https://pdfs.semanticscholar.org/c972/1dfeb562532929fdc9f05ad924e4276f2777.pdf

And apparently, fentanyl hydrazines can be made as well, as well as fentanyl thiocyanate (IIRC).

This has a lot of potential. The hydrazine derivatives bind once and are then bound until the receptor itself is destroyed in the lysosomes. This means it's continually agonizing for the receptors life span, and receptors generally last around 2 days, which is how long the azine derivatives last, two whole days. The agonism cannot be blocked by anything.

As well, the synthesis is exceedingly simple, hydrazine and acidic condition.

So I have two thoughts on this.

Firstly, I could see a very easy synthesis using morphine (either derived from codeine or from heroin that's been hydrolyzed in basic water), using palladium to isomerize it into hydromorphone (does raney nickel work for that too?), and then using hydrazine and acidic conditions to yield hydromorphazone, and then turn that all into hydromorphazine. This would have the incredible potency of hydromorphone (6.6x stronger than heroin), while having a duration of 48 hours, vs hydromorphones duration of 4 hours.

Sadly morphine hydrazine (morphazone/morphazine) cannot be made directly, because morphine has a hydroxy at the 6 position, while it seems necessary to have a carbonyl, because that's what hydrazine is reactive to. If this is not the case please let me know, it'd be a lot easier to just use morphine and attach a hydrazine at the 6 position somehow.

What's also an interesting idea is the injection of a azine derivative into the carotid artery. I know, I know, bare with me. Think about it like this: morphine administered ICV (directly into the brain, basically) is 100x stronger than IV morphine, meaning 1mg ICV is 100mg IV, the potency of IV fentanyl.

Now, DIY trepanning is impossible for us, but we could do something similar by administering the drug into the artery that feeds the brain with blood. Now, the problem with just using morphine via the carotid artery is that within a couple more heartbeats the morphine would be redistributed. But if you used the azine, all the morphazine has to do is bind once, which is easy for 1mg to do, once it's bound it's staying in the brain. Meaning, morphazine or hydromorphazine administered by injection into the carotid artery would be 100x the strength of morphine IV, and would last 48 hours. Isn't that just fucking amazing?

Now about carotid infusion. Carotid injections are done in animals without problems, and I saw an article about carotid infusions for certain patients. So it seems possible. I know it's bad when people inject into the femoral artery, but is that true for all arteries or just the femoral? Would it be possible to use a very needle? As well, the amount of liquid needed to contain all the morphazine/hydromorphazine would be small, a drop or two of water would be more than enough to dissolve the 1-5mg needed to get really really high. So it'd be barely any liquid at all. Possible?

Last thing. What if you made loperazine? Loperamide with a hydrazine at the carbonyl. Do you think that'd be possible, and would it be irreversible? Loperamide seems like it'd bind to the opioid receptor just like fentanyl, but it's held back by the chlorine. If you made it irreversible though, and administered it as mentioned before, you could get enough in the brain once, and that's all you need, all it has to do is bind once and you'd be high. Only downside I can think of, is that because loperamide's central efficacy is controlled primarily by P-glycoprotein, this could lead to major inconsistencies. For instance maybe one day PGP isn't working as well as before but you use the same amount of loperazine, boom too much bound and you can't be revived. This PGP inconsistency could be a problem. That said, loperazine could be a fentanyl like opiate that can be bought OTC.

Hydrazine can either be bought, or made from grocery store stuff like ammonia and hypochlorite/peroxide.

Any thoughts? I believe this is the future.

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