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Mexedrone (Apparent 4-MMC analogue)
(11-07-2016, 08:27 AM)SlowandFastandSlow Wrote:
(11-07-2016, 08:20 AM)Haihom Wrote:
(11-06-2015, 06:58 PM)roither Wrote:
(11-06-2015, 06:50 PM)dead-weight new Wrote: will be getting some in 1-2 weeks time will let u guys know

Nice! Can you tell us anything about the structure already? lol

Here we have some info abt mexedrone, a good stuff to experience with, it has been well delivered from China to UK by EMS Jul 2016.

Name: Mexedrone
CAS No. N/A to date
Molecular formula: C12H17NO2
A stims class chemical of cathione, you guys can find some info from https://en.wikipedia.org/wiki/Mexedrone.
Apart from the fact that it's illegal (is it? Is mexedrone even psychoactive?) Mexedrone has to have been the worst received chem since mephtetramine

    It is illegal to uk? i dont think so, there are some success delivery to uk. however there is legal in China. lots of possitive feedback of it, but not compare to mephtetramine, mephtetramine was created to be similar to cathinones, as you sid that users of this drug have received little to no effect, be considered to similar to 4mmc, but use with caution
Mate catch up it'll be covered by the NPS unless it is just completely inactive.

It's weak, but not COMPLETELY inactive. It's definitely covered, don't take the risk of importing it. It would be the most embarrassing substance ever to be charged with importing!
I Tried this recently meant to buy something else was sent mexedrone I think it was also mixed with another RC stim. Was actually really good shockingly I ground it down to powder and did fair sized lines but yer I was really surprised. Not recommending to people to buy it though might have just got lucky :P
A paper was published recently which throws some light on the whole mess that was Mexedrone:

Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone. McLaughlin G, Morris N, Kavanagh PV, Power JD, Dowling G, Twamley B, O'Brien J, Talbot B, Walther D, Partilla JS, Baumann MH, Brandt SD. Drug Test Anal. 2016 Aug 15. doi: 10.1002/dta.2053. [Link to paper on sci-hub]

[Image: r72Vjpk.png]

UKCR is referenced, specifically this trip report (and it's always nice to see our contributions to the pool of knowledge about these substances being recognised and properly attributed).

The study decribes the circumstances of mexedrone's release, the synthesis of mexedrone and a closely related substance N-methoxymephedrone, results from measuring their activity and provides some speculation on why mexedrone turned out to be so rubbish.

Quote:However, the months leading up to its release w ere intensified by a marketing campaign by online vendors, who only provided the website users with limited details such as the name of the new mephedrone analog, which was to be called "mexedrone" . During this time before its release, the authors attempted to predict the chemical structure of mexedrone. It was rationalized that the incorporation of a methoxy moiety to the terminal amine of the existing mephedrone molecular scaffold would be a suitable candidate for the NPS market, resulting in the formation of N-methoxymephedrone, 2-(methoxy(methyl)amino)-1-(4-methylphenyl)propan-1-one. This prediction agreed with a chemical structure of mexedrone that was later posted on a Polish vendor website. After its launch onto the market, however, the identity of mexedrone was reveal ed to be 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one. The prediction suggesting the addition of a methoxy moiety was correct although it was not incorporated into the amine as inferred, but rather it was attached to position 3 in the propan-1-one sequence.

Where have I heard N-mexthoxymephedrone before? I wonder if anyone else was thinking along the same lines as these researchers?

(20-08-2015, 08:10 PM)niamh Wrote: My prediction from a while back is methoxy on the amine in addition to the methyl. This would be 2-[methoxy(methyl)amino]-1-(4-methylphenyl)propan-1-one). This has the advantage of being fairly stable, not impossible to synthesize and there being similar compounds that exist and are known to be active (though not especially interesting, apparently). I'm actually more excited about finding out if I'm right about the structure than I am about the chemical.

The synthesis details are unlikely to be very interesting for people here so let's skip straight to the interesting bit where the researchers measure what mexedrone does (or, to be more accurate, doesn't do). This first table shows the potency of mephedrone, mexedrone and N-methoxymephedrone as reuptake inhibitors. The numbers represent the concentration required for 50% inhibition, so lower numbers represent higher potency. All three have activity, but both mexedrone and N-methoxymephedrone are a lot less potent as reuptake inhibitors than mephedrone and N-methoxymephedrone is significantly more potent at inhibiting the re-uptake of dopamine and norepinephrine than mexedrone.

[³H]DA uptake via DAT IC₅₀ (nM) [³H]NE uptake via NET IC₅₀ (nM) [³H]5-HT uptake via SERT IC₅₀ (nM)
Mephedrone 1056 ±85 494 ±93 470 ±7.6
Mexedrone 6844 ±1522 8869 ±3103 5289 ±1624
N-Methoxymephedrone 6091 ±1615 3457 ±728 3334 ±1129

The second table provides the potency of the same three chemicals as releasing agents. The numbers again represent concentrations requier red for 50% of the maximum release and lower numbers represent higher potencies. Here the differences become stark: Mexedrone is inactive as a releaser of dopamine and norepinephrine, and while it's active as a serotonin releaser, it has much lower potency than mephedrone. N-methoxymephedrone fares better, with lower potency but an effects profile that resemble mephedrone.

[³H]MPP⁺ release via DAT EC₅₀ (nM) [³H]MPP⁺ release via NET EC₅₀(nM) [³H]5-HT release via SERT EC₅₀ (nM)
Mephedrone 45 ±6 58 ±7 163 ±30
Mexedrone inactive inactive 2525 ±560
N-Methoxymephedrone 666 ±132 313 ±51 1043 ±271

Between them, these two sets of results provided by this paper show why mexedrone is an abject failure as an analogue of mephedrone: It lacks pharmacological effects that are central to mephedrone's activity. A weak reuptake inhibitor with weak serotonin releasing properties is nothing like a potent releaser of dopamine, norepinephrine and serotonin with moderate activity as a re-uptake inhibitor.

So why did the manufacturers go with the worst choice? If N-methoxymephedrone looks so much better on paper (still a long way from mephedrone, but at least in the same sporting arena of your choice) why develop and releaee the one that has the methoxy in the wrong position? Well, it turns out that N-methoxymephedrone has a serious disadvantage if you were looking to release it as a legal high:

Quote:During the characterization of N-methoxymephedrone, it was noticed that the compound had hygroscopic properties and that it was unstable in its crystalline form, and over time, would convert from a colorless solid to a brown solid. An additional chromatographic peak was noticed during LC-MS analysis of a second synthesized batch of N-methoxymephedrone. Examination of the analytical data revealed this impurity as mephedrons [...] it was concluded the mephedrone was present as a synthesis by-product.

Having an illegal drug a an impurity in your legal high rather defeats the purpose of developing an uncontrolled analogue of a controlled drug since you could get busted for possession of mephedrone and the legal high would be a de-facto controlled substance.

Quote:From this perspective, it is tempting to speculate that mexedrone was developed as an alternative to N-methoxymephedrone as it seems conceivable that mephedrone impurities in the latter compound would have been observed by manufacturers during the development stage. The pharmacological data suggest that N-methoxymephedrone showed a transporter-meditated releasing profile comparable to mephedrone although much lower in potency. By contrast, mexedrone was found to be a weak monoamine transporter uptake blocker and weak serotonin releasing agent, which might explain why this substance received poor reviews on user forums.

Or, in other words, the researchers speculate that N-methoxymephedrone was the initial target structure for mexedrone (early user reports were relatively favourable), but after the mephedrone impurity was discovered, they switched to the structure that was actually released (later reports were almost universally unfavourable). which doesn't have that problem, but also doesn't have the right effects profile to be remotely similar to the promises made in its marketing. This is a variant on the bait-and-switch tactics people speculated about, though the intention to switch substances would only have been formed once the non-viability of N-methoxymephedrone as a legal high had been discovered. This is speculative and we'll likely never know for certain, but the researcher's theory certainty seems to fit the facts, murky as they are.

So, in conclusion, mexedrone is demonstrably rubbish and it's entirely plausible that the early samples were N-methoxymephedrone, with mephedrone being a hasty and poor substitute once the problem with mephedrone impurities in N-methoxymephedrone was established. Most importantly, my speculation about the identity of mexedrone was right all along and I congratulate and thank the researchers for the hard work they put into demonstrating that it was not I, but the world that was incorrect. I look forward to being proven right in the many other instances where reality and my expectations have diverged.
Thanks for this info niamh, it certainly does explain a lot of things. It looks very probable that mexedrone only came about as a result of a last minute chemical switch at the last minute as vendors were determined to release something and get one last payday before the ban kicked in. I guess the inactivity of mexedrone as a dopamine and norepinephrine releasing agent explains the lack of stimulation (as opposed to the early batches where testers noted some reasonable stimulation).
Hello how are you
Another conundrum resolved. They should have released Fonazepam, Nitrazolam, Flunitrazolam instead of fleecing everyone. At least these are active. Still see Mexedrone for sale on EU sites, surely the message that it's inactive is now universally understood. Tried Ethyl Hexedrone when in Sweden and thought was plesantly nice in a MDAI ( with better stimulation) type way.
(12-02-2017, 07:32 PM)acetlyblue Wrote: Another conundrum resolved. They should have released Fonazepam, Nitrazolam, Flunitrazolam instead of fleecing everyone. At least these are active. Still see Mexedrone for sale on EU sites, surely the message that it's inactive is now universally understood. Tried Ethyl Hexedrone when in Sweden and thought was plesantly nice in a MDAI ( with better stimulation) type way.

I'm very confused by this. I think this got generally good reviews from the batches I received from Spain. It was slightly brown, though. Did the more inactive one not have this possibility of going brown at all?

Some people even told me they couldn't tell the difference between mephedrone and mexedrone (basically, you just needed a higher amount for the same result). Wedinos also tested it as mexedrone so that verified it too (as well as the Spanish supplier's own analysis). By the way, I had about 400g left before ChemicalWire bought it off me just a few days before the ban (so must have also been in demand, despite all the bad reviews).
So they stopped the first syth because of mephedrone impurity's.. huh.
Is that not a VERY common problem with 4 ACO DMT not impurity's but the fact that it degrades into psylocin?
Would anyone have noticed? At least the favorable response would have carried over after the release and who knows it could have been around as good as methylone or something. Which is way better than mexedrone.
love the world and it will love you back. chin

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