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Mephedrone Versions

Doclad

Doclad

Bluelighter
Joined
Mar 17, 2015
Messages
415
Goodnight.

I have a curiosity.:\

As you know 4-MMC has been a substance valued by people as very euphoric and addictive, but that is not important now.
4-MMC or Mephedrone belongs to the Catinones family (subfamily of amphetamines), since it has the double oxygen bond (beta-ketone). I was wondering if there has ever been a version of the molecule without the oxygen double bond, just as Methylone is the cathinone version of MDMA, which is amphetamine.

Many times the original amphetamine compound has been more relevant than the molecular model Catinone, for example, for many people 2C-B is above BK-2C-B, or MDMA on Methylone, both by effects and by requiring lower doses for a good trip.

Has the amphetamine version of mephedrone never been synthesized? Would not this compound be better in some cases? Have I missed something here?

MDMA - MDA - Methylone
?? - ?? - Mephedrone
https://en.wikipedia.org/wiki/Mephedrone


Thanks

DocLad
 
Yes, it exists. There isn't much info available though. I suppose it would feel similar to this one: https://en.wikipedia.org/wiki/4-Methylamphetamine (4-MA) is a known adulterant, at least in Dutch speed :? (https://nos.nl/artikel/383346-doden-na-gebruik-speed-met-4-ma.html)


That's mephedrone:
220px-4-Methylmethcathinone.svg.png



That's 4-MMA (4-Methylmethamphetamine)
220px-4-Methylmethamphetamine.svg.png
 
Doclad said:
Would not this compound be better in some cases?
Click to expand...

Honestly, I wouldn't try it. There haven't been published many studies and it could be similar (based on structure) to PMMA, which is a non-euphoric and dangerous compound...
 
Thanks for answering FlyingDutchman342.

Well, PMMA, from what I can see, it has a Metoxi group in the ring. I sense that it is toxic because of that.
At the moment, I have not seen any substance that by removing the beta-ketone group adds toxicity to a known amphetamine compound, for example MDMA / Methylone, I think it is no more toxic.
The deaths with 4-MA and amphetamines may be due to mixing, we do not know.
It seems to be a typical triple liberator, I do not understand why it would have to be dangerous.


Regarding 4-MA, it seems an interesting substance, although I doubt it could offer a different experience than Mephedrone. Here are some interesting facts:

4-Methylamphetamine (4-MA; PAL-313; Aptrol; p-TAP) is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes.

In vitro, it acts as a potent and balanced serotonin, norepinephrine, and dopamine releasing agent with Ki affinity values ​​of 53.4nM, 22.2nM, and 44.1nM at the serotonin, norepinephrine, and dopamine transporters, respectively. [1] However, more recent in vivo studies that involved performing microdialysis on rats showed a different trend. These studies showed that 4-methylamphetamine is much more potent at elevating serotonin (~ 18 x baseline) relative to dopamine (~ 5 x baseline). The authors speculated that this is because 5-HT release dampens DA release through some mechanism. For example, it was suggested that a possible cause for this could be activation of 5HT2C receivers since this is known to inhibit DA release. In addition there are alternative explanations such as 5-HT release then going on to encourage GABA release, which has an inhibitory effect on DA neurons. (WIKIPEDIA)

After the success of 4-MMC, I find it strange that 4-MA has never been spoken of.
If someone can throw some other data, I would be delighted.


DocLad
 
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Para-methylamphetamine is NASTY shit, don't even go there. Its well known as being highly toxic in vivo, and also capable of causing severe, long-lasting neurological/cognitive effects and depression.

Don't touch this one with a 20 foot shitty pole.

Also as a rule para-monosubstitution in an amphetamine is a recipe for something unpleasant. PMA, PMMA, para-haloamphetamines, 4-methylthioamphetamine, all bad news big time. 4-fluoroamphetamine seems to be the exception to this rule, although I still personally don't fancy it.
 
Thanks for your answer.

What is the mechanism of action that makes adding the beta-cetone group to create Mephedrone non-toxic?
I am surprised that this structural change has such an impact at the pharmacological level.


DocLad
 
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It isn't. If anything that beta-ketone makes the drug more hydrophilic than the amphetamine counterpart, thus requiring more of the drug to be administered to reach the desired effect. Definitely not a good thing with a 4-methylamphetamine analog.

If nothing else its going to mean more of the corresponding ephedrine produced as a metabolite and more cardiotoxicity.
Mephedrone and anything remotely like it are drugs I've always steered well clear of, haven't taken any of them, never going to, they are ugly little fuckers and bad news all round.
 
Wow, I had the feeling that the safety profile of Mephedrone was not so bad, considering the massive abuse for so many years, and except for some extreme cases, people have not had horrible long-term side effects.

DocLad
 
I suspect it's dose-related, as abuse of so many stimulants tends to be. Occasional weekend use is probably not as damaging as people going on 17-day benders.

Changing the para-substituted amphetamines to cathinones seems to decrease toxicity by decreasing affinity for monoamine release, I know that para-bromomethcathinone has been seen on RC markets, the cathinone analog of known neurotoxin para-bromoamphetamine. I haven't heard of any toxic reports from it, then again, it's been thoroughly advised against by almost anyone who has any pharmacology knowledge.

It could very well be that the cathinones are safer just from their hydrophilic nature and metabolic lability (reduction to ephedrines reduces activity a whole bunch and further decreases BBB penetration). The amphetamines' lower logP will mean longer persistence in the body and higher BBB penetration.
 
If you remember, PCA was originally released as an antidepressant, and originally didn't show itself to be a neuron-ablating serotonergic neurotoxin. The neurotoxic nature of the para-haloamphetamines was found out later (4-fluoro excepted, at least, it is thought so. Whether or not there have been studies done on it, I haven't looked. Although in a sense that tiny F atom is a bioisostere for hydrogen, and amphetamine itself (I.e para-hydrogen) isn't neurotoxic, at least not in any sense akin to para-haloamphetamines) Still, 4-FA isn't one I count as high-up on my to-do list all the same.

If you ask me (and just the same, if you don't) the fuckwits responsible for ever releasing 4-bromomethcathinone need boiling in acid from the toenails up slowly. I mean there is moronic and then there is releasing a virtual twin of a known outright poison.

EDIT-IMO that increase in hydrophilic nature in the cats is a double edged sword. On the one hand, in those that are inherently highly toxic, or should be so, going from the corresponding amphetamine, might be caused to reach the brain in lesser quantities/concentrations. On the other, in the case of those taken in bulk, and especially 4-XYZ substituted ones, then thats going to cause a lot of the corresponding ephedrines to be produced in-vivo and thus greater potential for cardiotoxicity.
 
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Taking advantage of this thread and not having to open a new one, I would like to ask you which family of empatogens looks healthier, taking into account the toxicity and possible side effects due to its pharmacology.
I know that the dose, the route of administration and other variables influence to a great extent, so it is a question perhaps not entirely technical.


Empathogens/entactogens
Phenylalkyl-
amines
(other than
cathinones)
Cyclized phenyl-
alkylamines
Cathinones
Tryptamines
Chemical classes


DocLad
 
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6-APB rectal was for me the most lucid and benign empatogenic trip of my entire life. I think the route of administration is important, right? It would be interesting to have a list of liver metabolites with their respective effects. I am sure that oral ingestion brings more side effects for that reason. After many experiences with MDMA and MDA by mouth, rectal 6-APB seemed much healthier and potent in every way. Should I expect the same from Mephedrone?

I am sorry to publish twice, that each one feels free to answer what they want.


DocLad
 
Generally speaking, rectal doses of amphetamines and friends (2C-x compounds, -phenidates) greatly increases their efficacy and decreases the amount needed for a dose, due to bypassing first-pass metabolism by the liver (thereby increasing BA). But don't get that mistaken, it doesn't mean that rectal use blocks all metabolic effects :)
 
It is curious that part of the toxicity of drugs is produced by the metabolites created by our own liver ... would there be any way to avoid it? I suppose it is a machine and it does not discriminate. I wish my brain could communicate to my liver how important it is that you are not doing anything on certain occasions!8)


DocLad
 
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Acetaldehyde? this is not an ethanol metabolite? Why do you mention it?


DocLad
 
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What about the potential as psychedelics of the overlooked backbone for 5HT2a receptor agonist psychedelics. RH-34, a substituted quinazolinonedione based skeleton, analogous to ketanserin with the sidechain swapped for an N-2-methoxybenzyl group.

We've got our tryptamines, amphetamines, phenethylamines, cathinones, ergolines, but here is another very little explored backbone for 5HT2a agonists.
 
Greetings Limpet_Chiken.

Can you develop this last post a bit more? I'm very interested.

Thank you


DocLad
 
Look up the structure of RH-34 on wikipedia. Its a 5HT2a partial agonist of medium efficacy. Essentially its ketanserin, a serotonin 5HT2aR antagonist which is used in many assays of serotonergic systems, with the sidechain ripped off and replaced with a 2-methoxybenzylamino group which is connected to the ketanserin backbone by an ethyl bridge anchored to the nitrogen located between the two carbonyl groups.

Remember with the phenethylamines etc. how various N-benzyl sidechain extended phenethylamines, amphetamines etc. and substituted N-benzyl groups bearing substituents on the phenyl ring of the N-benzyl group become highly potent 5HT2a agonists, aka the 'bomamines' and similar? in the case of tryptamines this same N-benzyl amine substitution churns out antagonists, possibly very low efficacy partial agonists, but that have very high binding affinity to 5HT2a.

But in the case of modifying ketanserin this way, there are both, antagonists and some agonists, that are at least moderately efficacious partial agonists. Not sure about the binding affinities vs ketanserin or radiolabelled DOI, but this is an entire new scaffold for development that isn't just a cathinone, a conformationally constrained or ring expanded cyclized amphetamine like say, the 2-aminoindans, 2-aminotetralins etc, not a tryptamine with the phenyl ring changed for an aliphatic cyclic ring or the indolic nitrogen changed to give a benzothiophene, but something wholly new and begging to be explored Sasha style for the next generation of psychedelics. A moderate efficacy 5HT2a partial agonist is a good sign IMO, for potential safety, compared with the likes of the NBOMe phen/phet/cats which often show very high efficacy as well as low single digit nanomolar or less affinities.

Its just that there is this little known pharmacophoric core, which has been shown to produce potential psychedelic candidates with good 'druggability', and whilst there are a couple of such derivatives known as agonists, I mean, just try and tell me you don't see the ergolines, tryptamines, amphetamines, phenethylamines, cathinones and the various flys, hemiflys, dragonflies and dearomatized ring expanded tryptamine type analogs, its there, it hasn't been mercilessly systemically modified, affinity/efficacy tested with binding assays, as well as of course made and tasted. Just tell me that every possible substituent on that benzyl group needs to be tested, multiple substitutions assayed, the quinazolindione core modded in every way possible by clandestine chemists the world over with a taste for more than the low hanging fruit of meth, speed, MDxx, GHB, chloral hydrate etc, and who have running in their veins a predilection for chemical artistry, striking out to pave new roads to new chemical families and when found, exploring the fucking christ out of all that can be coaxed from them.

Ain't that the finest peak of the art that a clandestine chemist can ever aspire to? to break such new ground, and to tread side by side with the ghost of Sasha Shulgin, may his soul have found eternal bliss and be soaring with the machine elves through hyperspace, and with the essence of David Nichols watching over his other shoulder and heaping blessings upon their flasks and benedictions over the vacuum pumps and condensers.
 
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