Why Dextromoramide is so great and why nothing will live up to it

[blueberries]

I was puzzled as to why DMM wasn't as great as DM so I put them both into Swiss Target Prediction and found that what makes DM so wonderful and DMM so crap is....Cytochrome P450.

It makes perfect sense and DM is definitely a ligand whereas DMM isn't whatsoever. The Oxo seems to be fairly essential though I haven't yet tried it without it. It could even work better as a Hydroxy but when the US government makes a drug, they make them fucking wonderful!

Here are my STP results:



I tried the majority of the most basic analogues and got some interesting results.

It seems that DM agonises the Cytochrome P450 enzyme increasing the amount of serotonin and dopamine (which is also being released) in the blood into all the receptors.

So it's like mishmash of dopaminergic channels going mad and opioids are dopaminergic compounds thus get caught in the rapids!

It's an odd compound. A very odd compound.

 

[4meSM]

It seems that DM agonises the Cytochrome P450 enzyme increasing the amount of serotonin and dopamine (which is also being released) in the blood into all the receptors.

What do you mean? I don't see a clear connection between CYP450 and dopamine or serotonin. I believe those neurotrasmitters are mostly metabolized by MAO (monoamine oxidases) but not by CYP450 enzymes which are mostly found in the liver (though small amounts are also expressed in the brain and in other tissues).

Swisstarget is likely just predicting that the compound may act as an inhibitor of some CYP450 enzymes. Inhibition of CYP450 is usually considered as undesirable by pharmaceutical companies because it increases the probability of dangerous drug-drug interactions (they always look into that when exploring new potential drug candidates).
Those results must be taken with a grain of salt IMO... It didn't even predict any affinity for MOR despite being an opioid.

 

[blueberries]

I remember doing a lot of research a long time ago on CYP450 and it was to do with serotonin and dopamine releasing channels. I could be wrong though, I'll have a quick recheck and edit/delete as necessary.

Ok; so essentially P450 is responsible for breaking down neurotransmitters hence why when you drink orange juice it can increase the effects of opioids. If one were to reduce the activity of P450 then dopamine and serotonin would flood the brain, not to mention endorphins and other opioid ligands.

So why doesn't grapefruit juice produce the same effects as Dextromoramide? Simply because DMM has extrapyramidal effects like opioid agonism and SDRA. This coupled with the CYP450 creates a perfect storm of euphoria that emanates from this compound.
In fact it works too well so they removed it from shelves!

It /is/ however something to think about when needing to cut costs on drugs and their combos in the future.

Just a few mg of a certain selective enzyme inhibitor could save millions at the end of the day. Imagine using 1mg of Oxy and ~0.5mg of CYP34A (the enzyme responsible for degradation of opioids such as methadone, morphine, codeine (whole list is here: https://en.wikipedia.org/wiki/CYP3A4?wprov=sfla1)) and getting a 20mg affect from it. Who's to say they aren't doing that now? Is that why American Xanax feels different to EU Xanax?

I'm veering quickly off the conspiracy cliff here but certainly what's to say that it couldn't happen in the future? When drugs become legal we could use them in much, much smarter ways. In fact I think once the people take over drug composition it'll be a bit mad in the first few years but after a while this will be just the first milestone on a path to somewhere wonderful.

EDIT: Also the fact that it didn't show up much on any opioid channels is what made think of this. How can an opioid be an opioid if it has very little opioidergic action? Enhancement.

 

[emkee_reinvented]

Without using this or Heroin myself.

Anecdotal information from user's, back then, seem to indicate that Dextromoramide oral is at least equally to IV Heroin.

Rush wise. But the absorption is un-logic a dose that get's you high one time doesn't do any thing the next time. A dosage what does nothing kill's you next time.

Be safe!

 

[blueberries]

This is another example of why P450 inhibitors must have been used instead!! I mean you take meth or MD along with a P450 and you're dead as a doornail.

Thankfully I've been trying to feel this DMM all night so I abstained a bit from dope but my god; my girlfriend is going absolutely crazy at me for basically nothing. It's like she's on her period but by a factor of ten. She is on amphetamine.

Actually I need to watch what drugs I do now. I did some benzos about half an hour ago and can /actually/ feel them (I haven't felt benzos (except /really/ strong ones like Flunitraz) in /years/, now 3 Lorazepam have me close to sleep (I'm also on speed but a lot less and I only had two doses of about 20mg each (DMM) over a couple of hours ~6hrs ago).

 

[emkee_reinvented]

This is another example of why P450 inhibitors must have been used instead!! I mean you take meth or MD along with a P450 and you're dead as a doornail.

Not me, although this statement seems a little exaggerated.

Ime experience taken before MDMA was unnoticeable beside's a vague feeling that could have been placebo.

On paper it would have prolonged the experience. If CYP450 is significantly inhibited by the juice and MDMA is broken down through this pathway exclusively.
Not kill you.

 

[Tryptamite]

No.

 

[Skorpio]

Not me, although this statement seems a little exaggerated.

Ime experience taken before MDMA was unnoticeable beside's a vague feeling that could have been placebo.

On paper it would have prolonged the experience. If CYP450 is significantly inhibited by the juice and MDMA is broken down through this pathway exclusively.
Not kill you.

There are a whole plethora of p450s too. Mdma is actually an extremely potent mechanistic inhibitor of cyp2d6 (basically the methylenedioxy methelyne gets oxidized to a carbene which attacks the heme group of 2d6. Paper citing it basically says it's so potent that it means genetic cyp2d6 variation isn't an issue with mdma because of how rapidly and thouroughly it inhibits the enzyme.

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[blueberries]

Shit...what's the one that enhances SERT then? Because I need that one and the one that enhances opioid receptors.

I still have fucktons of it because while I reckon I have been getting an effect from around 40mg+ it could well have been a placebo.

Regardless it's 50% dextromoramide no? Or does the isomer just completely change the affect and leave nothing for the racemide?

 

[blueberries]

Shit...what's the one that enhances SERT then? Because I need that one and the one that enhances opioid receptors.

I still have fucktons of it because while I reckon I have been getting an effect from around 40mg+ it could well have been a placebo.

Regardless it's 50% dextromoramide no? Or does the isomer just completely change the affect and leave nothing for the racemide?

Ok I'm going to try Clemastine (Tavegyl) tonight. It's OTC in my country and it seems to inhibit 2d6 fairly well (and one of the only ones; thank fuck it's OTC here!).

 

[Tryptamite]

Beach palfium was notorious for giving inconsistent bioavailability and effects true a variety of routes of administration day today de-ale art more study needs to be done one.on this now the front med before we can really know anything about it it although no it was meant to be be the bee's knees

 

[fastandbulbous]

Beach palfium was notorious for giving inconsistent bioavailability and effects true a variety of routes of administration day today de-ale art more study needs to be done one.on this now the front med before we can really know anything about it it although no it was meant to be be the bee's knees

Beach palfium? You mean tablets found by the seaside?
Sorry, I know you mean peach (the 10mg pills). As far as I'm aware, it was only available for breakthrough cancer pain, but was withdrawn due to producing an unacceptable degree of respiratory depression, for it's analgesic effect (and that it was horribly toxic in combination with alcohol/CNS depressants).
As regards cytochrome p450, thete are a shitload of isoenzymes that fall under the cyp450 label. Some are connected with specific actions eg cyp3A4 tends to be the enzyme the N-demethylates (N-dealkylates) a whole range of compounds. Inhibiting the same enzyme can be very serious, as it is responsible for the main metabolic route of statins, such that a statin and cyp3A4 inhibitor can lead to to muscle breakdown, which releases myoglobin into the bloodstream. Myoglobin really fucks up the nephrons that make up the kidneys. While the less potent cyp3A4 inhibitors like bergamotin (found in grapefruit juice) aren't that much of a problem, unless drunk in silly amounts, very potent inhibitors, like the antibiotic clarithromycin, can cause an incredible amount of toxicity problems. Due to the huge diversity of p450 isoenzyme forms, it really is a topic that could fill several textbooks. They also play a role in making virtually inactive drugs, like codeine, into their more active metabolites (cyp2D6 tends to O-demethylate compounds), namely morphine. The degree of activity is also dependant upon the degree of gene expression, for each isoform., so can differ wildly between individuals, even of the same racial group.
Finally, p450 enzymes evolved more for the removal of toxins (first pass metabolism of anything absorbed from the GI tract), than the metabolism of neurotransmitters (the main neurotransmitters involved in the rewarding actions of drugs, are metabolized by monoamine oxidases).

 

[unodelacosa]

EDIT: Also the fact that it didn't show up much on any opioid channels is what made think of this. How can an opioid be an opioid if it has very little opioidergic action? Enhancement.

Exactly. Consider Tapentadol and Tramadol and how their µ-opioid affinity is synergistically enhanced by norepinephrine or serotonin modulation, respectively.

Nice post!

 

[izo]

I might get my hands on some desmethylmoramide can report back after i got it.

 

[unodelacosa]

I might get my hands on some desmethylmoramide can report back after i got it.

I’m guessing this is an active metabolite of dextromoramide and should be more or less on par with its effects, but just from reading about it, that doesn’t seem to be the case. Its potency is less than that of dextromoramide, and the qualitative effects appear to be rather ho-hum. Your experience might be totally different of course, but in terms of popularity, dextramoramide > desmethylmoramide. Come to think of it – I wonder if desmethylmoramide is racemic typically, or what? Levomoramide apparently is inactive and this could cut the potency in half, theoretically, at least if comparing a racemic version of desmethylmoramide to d-moramide.

 

[allone]

if tianeptine was longer acting, in high doses, its probably better. all the morphine related drugs ive tried didnt come close to high dose tianeptine. but again, its short action makes me not very desirable plus its longer lasting stimulating effect is a bit irritating for most.

 

[blueberries]

Just to conclude this post; I'm trying to make a novel dM analogue that will actually work at full activity without any bullshit like with DMM. I'll send it to China because the Swiss checked out at New Year (I don't blame them, they've been in the game since even I started!!). They were a wonderful company, extremely kind but also didn't put up with any bullshit, aka; me begging them to make 2C-EF(!) yet they alway had the rarer compounds, I became an unofficial tester for them and as a result, tried many, many more compounds than were actually released (it's the same with LF and Jimmy in China).
They gave me the /biggest/ opportunity to hone my design/pharma skills and for that I'll be eternally grateful.
Thank you for 10 years of consistency, 10 years of politeness, 10 years of kindness and 10 years of some bloody great ideas!!
Raise a glass to the Swiss; then I'll email LF with a working DM analogue.
Cheers!

 

[unodelacosa]

Just to conclude this post; I'm trying to make a novel dM analogue that will actually work at full activity without any bullshit like with DMM. I'll send it to China because the Swiss checked out at New Year (I don't blame them, they've been in the game since even I started!!). They were a wonderful company, extremely kind but also didn't put up with any bullshit, aka; me begging them to make 2C-EF(!) yet they alway had the rarer compounds, I became an unofficial tester for them and as a result, tried many, many more compounds than were actually released (it's the same with LF and Jimmy in China).
They gave me the /biggest/ opportunity to hone my design/pharma skills and for that I'll be eternally grateful.
Thank you for 10 years of consistency, 10 years of politeness, 10 years of kindness and 10 years of some bloody great ideas!!
Raise a glass to the Swiss; then I'll email LF with a working DM analogue.
Cheers!

To the Swiss

Yes, 2C-EF sounds nice. Maybe one day.

Its alpha-methylated analog (amphetamine instead of phenethylamine) must be very, potent, I would imagine. DOEF? Well, kinda… 2-3.5mg of DOEF is listed as standard, but I don't believe it takes very much 2C-EF to be sent to the moon. And of course, taking things to extremes would be the trifluoromethyl compounds, 2C-TFM and DOTFM. All very interesting.

 

[arrall]

Really hope that we get to see the development of 2C-x (and by extension, DO-x) compounds pushed to its limits sometime in the next few decades. There's so much (some half-developed in PiHKaL but never synthesized) that Shulgin never got the chance to make.