Explaining the residual stimulation of methylone

[aced126]

Why is methylone way more residually stimulating than its brother MDMA? Could it be due to this metabolite?

Or even this one:

Seems to perfectly satisfy everything needed for a potent beta agonist. And along with the fact that the dosage is higher, could all this contribute to the above observation?

 

[Solipsis]

Methylone forms 3-hydroxy-4-methoxies or 4-hydroxy-3-methoxies... That catecholamine like freak - the bottom one there ^ - would probably be devestating to your CNS .. neurotoxic i bet

(Meth)cathinones like mephedrone were indeed found to produce beta-hydroxy metabolites that are heavy on the cardiovascular system.

Dose being higher could be partially due to different binding? bk-2C-B needs pretty huge doses right? But that does produce the BOHB metabolite that is actually supposed to be rather great (still have not tried my BOHB yet so sorry to say) but also other side products. And I am not 100% that the dimerization story was solved, maybe it is not such a huge issue to make beta-keto primary amines if preserved well... but I would still factor that in.

 

[aced126]

That catecholamine like freak - the bottom one there ^ - would probably be devestating to your CNS .. neurotoxic i bet

True; I'm tending to think it wouldn't really get into the brain much anyway though, unless it is unmasked in the brain itself. I do think that one or something like that, especially with the beta hydroxy, is responsible for the amphetamine like residual stimulation which keeps you up entirely the next day, and that's something which doesn't happen at all the MDMA.

 

[raising_da_piggy]

i have found the methylone experiences transitional period before a come down to be abrupt but possibly not as irratating as the drawn out mdma fuzzy stage after the high! i used the product wich was called explosion, there was two versions and they were both in little bottles, one made me hallucinate and see objects waver, and the other was more mdma stimulant, was told they were methylone...

 

[dopamimetic]

The methcathinones have this really nasty side to them, the only one I've used repeatedly was 3-MMC and I could only tolerate very small dosages (<20mg) that were more of a plain stimulant - but one that is less cold than e.g. amphetamine - because of the build-up of 3-methylnorephedrine (if I'm right) and even then I got heavy tachycardia and some anxiety from time to time and had to take clonidine for comedown.

It would be a really nice stimulant if the metabolism could be changed (but this is impossible of course).

 

[Cotcha Yankinov]

The stress hormones do indeed stick around for a while.

My experience with methylone was not sleeping for 4 days, mild psychosis, and HPPD forever thereafter, suppose the not sleeping part fits pretty well if it's a beta agonist. I would love to know the neurotoxicity of it, or if the toxicity is mostly related to the sympathetic stimulation. I seem to not be able to handle any sort of adrenaline anymore, even caffeine gives me horrible side effects.

 

[sekio]

I would suspect the damage, if any, came from staying awake for 4 days. It's been my long standing belief that most anxiety related "damage" from MDxx is psychological, not a manifestation of physical damage.

MDMA is actually far more persistent in the body than its effects profile would indicate, and yet it generally does not cause super strong insomnia unless recklessly dosed. So it's not due to monoamine release alone. Like others have stated I would suspect that methylone or its ephedrine metabolites would be good adrenergic (alpha or beta) agonists. Combined with large scale NE release and consequent 5HT depletion after the peak, I'd expect the insomnia generating effects to be amplified relative to MDMA - even though as a more polar molecule, you would expect methylone & metabolites to be excreted faster than MDMA.

Oh, also, it could also be due to methylone's higher affinity for causing NE release than MDMA does?

 

[Fractality]

I would suspect the damage, if any, came from staying awake for 4 days. It's been my long standing belief that most anxiety related "damage" from MDxx is psychological, not a manifestation of physical damage.

Can you elaborate further? Typically, the MDxx experience is psychologically positive, so why would there be negative after-effects related to that? Or are you implying that when one returns to baseline, one misses the psychological state that MDxx provides, and that in turn causes anxiety?

 

[aced126]

He is saying that whenever people get anxiety, they always want to blame it on something and MDxx is something you can easily blame it on (as there are so many stories of people suffering from anxiety after MDxx abuse).

 

[Dresden]

Oh, also, it could also be due to methylone's higher affinity for causing NE release than MDMA does?

This.

 

[aced126]

This.

On wikipedia it says it has the same affinity as MDMA at DAT and NET, but 3x less at SERT. Obviously the higher dose could explain it, but I feel like after some time the NE response should be over, and there are other contributing factors at work.

 

[Dresden]

Well, yeah, the molecule of methylone itself has a benzyl oxo group which is reduced to a benyzl hydroxy group. Both of these benzyl oxy substituents contribute to methylone's adrenergic effects and are not an issue with MDMA or MDA.

ADRENALINE aka EPINEPHRINE

A MAJOR METHYLONE METABOLITE

Comparing the molecular structures of these compounds is highly instructive with respect to answering this question and leaves little doubt in my mind about what that correct answer is, but I will admit to being quite the member of the chemical structuralist school of pharmacological thought and design.

 

[dopamimetic]

I'd still say that it is mostly the methylendioxynorephedrine(?) metabolite causing the residual stimulation, as is the case with 3/4-MMC.