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Stimulants of the Future

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nuke said:
So...phenmetrazine derivatives. Why on Earth did methylone come before 3-methyl-2-(3,4-methylenedioxy)-phenylmorpholine? I wonder if the activity is closer to MDA. Para-methoxy-phenmetrazine? Hmm.. I'm guessing there's a good reason I don't know why these never happened.
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I suppose the reason is that methyone works in a similar way to MDMA the morpholines are much more likely to be simple stimulants. As far as I am aware there is not a lot that can be done to the side chain of MDMA without the sparkle disappearing. N-hydroxy is OK and that is about it.
its shame that in order to get MDMA like effects the molecule has to be fairly indescriminate, adding bits on or locking up the side chain improves the selectivity serotonin versus DA but the magic is gone.
 
Smyth said:
have u ever seen the patent for phenmetrazine? [The synthesis is a bitch]
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Mr Mod please delete if this is too synthesis based

surely it can be synthesised from the diketone or oximino ketone, both of which have been used in historical adrenaline synthesis.
alternatively it should be possible to go through the B hydroxy amine.
 
Smyth said:
have u ever seen the patent for phenmetrazine? [The synthesis is a bitch]
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It's not - it's a condensation of norephedrine & 2-iodoethanol followed by dehydration with sulphuric acid (no I'm not going to give details as that's verboten). Equally bromopropiophenone & 2-aminoethanol gets you to the same pre-dehydration place.

I wouldn't give up on the methylenedioxy analogue of phenmetrazine as it is capable of attaining the conformation of MDEA and isn't the beta hydroxy or methoxy analogue od MDA active?
 
Yes, BOB-MDA is active. Desirable? Perhaps not.

The MDO phen(di)metrazine analogues may be active but are most likely less desirable than the original MDxx series.
 
fastandbulbous said:
I wouldn't give up on the methylenedioxy analogue of phenmetrazine as it is capable of attaining the conformation of MDEA and isn't the beta hydroxy or methoxy analogue od MDA active?
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beta-methoxy-3,4-MD-phenylethylamine is active (pihkal #15) so presumably the amphetamine analogue would be active also although not sure if it has been tested?

One compound i would be interested in would be the 3',4'-methylenedioxyphenyl analogue of 4-methylaminorex...the 4'-CF3-phenyl and 3',4'-dichlorophenyl analogues were highly active appetite supressants and more serotonin selective than the parent compound, so the methylenedioxy derivative might also be worth a look.

Indeed many of the amphetamine-derived stimulants are unsubstituted on the phenyl ring, so in theory methylenedioxy analogues could be made for any of them...how about the 3,4-methylenedioxy analogue of fencamfamine etc....or for that matter, even the corresponding cocaine analogue could be good, seeing as 3',4'-dichloro-cocaine is more active than the parent, and blocks both serotonin and dopamine reuptake (so less selective than coke, but with recreational drugs, "messy" binding is not always a bad thing)
 
If you're looking for stimulants, then yes they might be more active as dopamine reuptake inhibitors, but if you're looking for entactogenic activity it's not as simple as just sticking a methylenedioxy group on the phenyl ring (it's a lot more complicated) of a series of stimulants. The reason I mentioned the MD analogue of phenmetrazine is because it has a reasonable chance of entactogenic activity; bunging it on 4-MAR, fencamfamine isn't going to be effective simply because of the limited conformation of those ring structures
 
mad scientist is thinking in the right direction.

Personally, I like stimulants, but any new entactogens are tres wilkommen.
Also, I don't know that the 3,4-dichlorophenyl thingies are either pure entactogen or pure stimulant or what. The 3,4-dichloromethylphenidate analogue is said to be the most rewarding of that series, which would to me indicate stimulant action.

This direction of study merits research.
 
keepin' it simple / back to basics

'Stimulants of the Future': 3,4-dimethoxymethamphetamine HCl.

C'mon, guys, I know you can pull this one off with a little dimethylsulphate and some other standard items. The 'geometric colored objects' [see PIHKAL] observed with 3,4-DMA in mental patients intrigues me more than just a little bit.

One time, in my dorm room, after binging on some good crank and smoking a bowl of weed, I saw a rotating, glowing green triangle in the air. It was awe-inspiring.
 
fastandbulbous said:
This has the extra advantage of being a few easy staps from phenylalanine (via phenylalaninol) rather than having to fuck around with expensive things like pipecolic acid & nast organometallic compounds (Grignard or organolithium)
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I'm a little skeptical about that since I can't think of a way to reduce a carboxylic acid all the way to an alcohol without using a nasty LAH.
 
^ok (maybe pressurized catalytic hydrogenation), but how hard would it be to give some anhydrous methanol, 3,4-dimethoxyphenylacetone, MeAm and NaBH4 a spin?

:)
 
reasons why 3,4 DiMeO meth is a waste of time

hussness said:
I'm a little skeptical about that since I can't think of a way to reduce a carboxylic acid all the way to an alcohol without using a nasty LAH.
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or you could simply buy the phenylalaninol.

helios- I don't think anyone is at all interested in 3,4 dimethoxymethamphetamine. the reasoning is simple.


if you expect it to be an entactogen like MDMA then one would expect the primary amine to show some entactogenic activity a la MDA. It doesn't, heroic doses have been eaten in the past.

then look at the modifications that can be made to the dioxole moety of MDMA adding a single carbon to the bridge carbon in MDA (to make EDA) all but abolishes activity . The dimethoxy groups of 3,4 dimethoxyamphetamine are easily as bulky as EDA's, and they are not constrained, therefore it is very very very unlikely that it will form a confguration like MDA or MDMA.

However the MethylMethoxyamphetamine is reported to substitute for MDMA to an extent.

As a side note 3,4-dimethoxy methylamphetamine would be produced from ingestion of 4-chloro methamphetamine, not that eating 4-chloro methamphetamine is a good idea at all.
 
fastandbulbous said:
Rather than go for 2-benzylpiperidine, the logical target should be 3-benzylmorpholine as of the the diphenylmethyl substituted heterocyclic compounds, the original paper reported the morpholine derivative to be by far the most potent locomotor stimulant in trials.
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What is this reference? I just did an ACS journals search and turned up with nothing.
 
Hey, you could synth that from vannillin very easy with DMS, followed by standard Amp preparation from the aldehyde.
 
vecktor said:
or you could simply buy the phenylalaninol.

helios- I don't think anyone is at all interested in 3,4 dimethoxymethamphetamine. the reasoning is simple.


if you expect it to be an entactogen like MDMA then one would expect the primary amine to show some entactogenic activity a la MDA. It doesn't, heroic doses have been eaten in the past.

then look at the modifications that can be made to the dioxole moety of MDMA adding a single carbon to the bridge carbon in MDA (to make EDA) all but abolishes activity . The dimethoxy groups of 3,4 dimethoxyamphetamine are easily as bulky as EDA's, and they are not constrained, therefore it is very very very unlikely that it will form a confguration like MDA or MDMA.

However the MethylMethoxyamphetamine is reported to substitute for MDMA to an extent.

As a side note 3,4-dimethoxy methylamphetamine would be produced from ingestion of 4-chloro methamphetamine, not that eating 4-chloro methamphetamine is a good idea at all.
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4-methoxy-3,N-dimethylamphetamine would be a good one to try, as 3-Me-4-MeO-A is supposedly similar to MDMA (in Nichol's rats anyway)

And for that matter, 2-methyl-MDA and 5-methyl-MDA were more active than MDA, with the 5- being strongest. So maybe 2,5-dimethyl-MDA might be worth a look, although that might make the ring too bulky...or perhaps 4-MeO-3,5-diMe-A...or their N-alkyl derivatives....many possibilities.
 
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mad_scientist said:
4-methoxy-3,N-dimethylamphetamine would be a good one to try, as 3-Me-4-MeO-A is supposedly similar to MDMA (in Nichol's rats anyway)
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3-Methoxy-4-methylamphetamine is pretty much like IAP in that it is serotonogic but without much in the way of dopaminergic activity - N-methylation isn't going to suddenly make it magically like MDMA (I've tried N-methyl IAP - IMP as a friend playfully named it! - & it wasn't any sort of noticable improvement over IAP). To get the entactogenic activity, it seems that the 3-O atom nees to be constrained, not flopping around as in 3-methoxy-4-methylamphetamine (to do with lone pair orientation).

A good bet would be 6-(2-(methylamino)propyl)-2,3-dihydrobenzofuran - MDMA with the 4 oxygen replaced by a methylene group, or equally the primary amine compound (analogous to MDA). The compound with the methylene group in place of the 3-oxygen (referring to MDA not MDMA) is active but doesn't quite tick all the boxes of entactogenic activity and is best described as 'strange' (although the person calling it strange said he'd repeat it at the 200mg dosage level). Apparently the one I mention above is a bit more difficult to synthesize, but I'd recon it'd be well worth it.

Maybe at this point it's worth considering the pharmacology of mixtures of drugs. In a simplistic move, I tried combining IAP (serotonogic component) with amphetamine (dopaminergic component) and got a combined result that was more than passable as MDA in effects. This sort of simplistic approach doesn't always work, but as long as it's not contraindicated, it's definitely worth a try sometimes!
 
vektor do your homework

Quote: 3,4-DMA, PIHKAL, p. 605:
A few non-military studies have indicated that 3,4-DMA is orally active at 160mg, and so probably its potency by this more conventional route would fall midway between that of mescaline and MDA.

What do you have to say to that?
What are you going to claim next, that TMA is not active either?
 
A few non-military studies have indicated that 3,4-DMA is orally active at 160mg
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Every study I've seen has stated that 3,4-dimethoxyamphetamine is inactive even at the 500mg dosage range other than some adrenergic activity (but no proper psychedelic or entactogenic activity). I'm tempted to say it looks like a typo and there should be another 0 at the end ie 1600mg or that the 160mg refers to 4-methyl-3-methoxyamphet but was misread. Without specifically citing the studies saying that, it's a bit hard to believe (remember this is just Shulgin repeating second-hand info - the original info could be corrupted or plain wrong; If there's no activity with that dose via IV, then it's not going to be more potent orally; it appears to take 600-700mg via IV to elicit psychedelic effects, so 160mg orally doesn't have a hope. Such things are always the other way around ie IV is always more potent than oral route.

Larger alkoxy groups on the 4-position produces compounds with activity under 500mg via the oral route, but not the 3,4-dimethoxy
 
fastandbulbous,
^so 3,4-DM(M)A is inactive, but 3-methoxy-4-(n)-pentylamphetamine is probably not inactive.
What is the word on 4-hydroxy-3-methoxy-(meth)amphetamine?
 
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