4-methylamphetamine?

[pofacedhoe]

we have mephedrone which is 4 methylmethcathinone

but what about 4-methylamphetamine? would it be euphoric, has anyone tasted it????

 

[fastandbulbous]

Reports about 4-methylamphetamine do not sound encouraging although the original stuff is in Russian (I saw some that someone had kindly translated, but that was a while ago - on the Hive I think)

 

[Riemann Zeta]

The interesting thing is that according to the in vitro numbers, 4-methylamphetamine should be a nearly perfect MDMA-like compound, with an EC50s for [3H]DA and [3H]5-HT release of 44.1 nM and 53.4 nM, respectively (Rothman & Baumann, 2006). Since so many people seem to like MDMA (I myself prefer a traditional dopaminergic/noradrenergic amphetamine like dex, but to each his own), one would think--at least a priori--that this one would be a winner. Is there some sort of nasty side effect in humans? I mean, being a mono-4-substituted amphetamine, the compound does kind of sketch me out: I would be worried about the possibility of 5-HT2B receptor activity. Then again, MDMA itself is pretty damn sketchy--those oxygens are trouble waiting to happen and perhaps a compound lacking them would not generate a toxic metabolite in vivo like MDA/MDMA/MDEA do.

 

[dread]

How about sticking a 3-methoxy group on that?

 

[fastandbulbous]

^ It'd end up being almost exclusively serotonogic in action - lacking the dopaminergic activity that makes MDA/MDMA special

 

[Hammilton]

AFAIK, all of the 4-subbed 2b agonists have a pretty bulky sub, and all of the truly dangerous 4-subbed things like PMA some of the 2-CT's have a methoxy or methylthio (obviously something important about that oxygen or oxygen-like atom for MAO inhibition).

 

[ebola?]

>> It'd end up being almost exclusively serotonogic in action - lacking the dopaminergic activity that makes MDA/MDMA special>>

Well, if we accept your claim that IAP + d-amp = MDA (or nearly so), then wouldn't the future of drugs be highly specific agents put in combinations for desired effects?

ebola

 

[dread]

AFAIK, all of the 4-subbed 2b agonists have a pretty bulky sub, and all of the truly dangerous 4-subbed things like PMA some of the 2-CT's have a methoxy or methylthio (obviously something important about that oxygen or oxygen-like atom for MAO inhibition).

By that logic, shouldn't mescaline be a MAOI? Or 2C-O?

Actually, is it possible that 2C-O has some MAOI activity? They say it potentiates mescaline if taken 45 minutes before. Sounds like a MAOI...

 

[Riemann Zeta]

^^(two up)^^Well, polypharmacy is what being a modern-day pharmacoalchemist is all about. However, sometimes a "dirty" drug really gets the job done and is far more efficient that a bunch of hyper-selective individual compounds.

^(one up)^I think that any substrate for MAO can technically be considered an inhibitor at the proper dosage, by virtue of it taking up the enzyme's time, preventing it from metabolizing other substrates. Accordingly, any amphetaminergic monoamine transporter substrate is also going to act as an uptake inhibitor, simply because it is competing with the endogenous substrate for transporter time.

 

[Riemann Zeta]

Mea cupla for bumping my own last reply, but I'm digging this thread back up because the title compound might be potentially interesting shit. Does anyone have any binding data for this compound at the 5-HT2B receptor? I searched, but honestly couldn't find anything out there on the intertubes other than the transporter affinities. Other recently-investigated serotonergic amphetamine derivatives (such as alpha-methyl-naphthylethylamine, aka PAL287) do have an untoward affinity towards the 5-HT2B receptor. If this one doesn't, I still think that it is a very promising replacement for MDA/MDMA: it has a nice and balanced dopaminergic/serotonergic ratio and the 4-methyl moiety would block metabolism into a toxic pro-oxidant 3,4-dihydroxyamphetamine compound. A compound possessing the empathogenic/antidepressant/anxiolytic effects of MDMA without the oxidative neuronal damage would clearly be a winner--both as a harm-reducer for those taking MDMA recreationally but also for clinical purposes. I suppose the compound's efficacy as an MAO-A inhibitor also needs to be tested, as that is what makes PMA such a dangerous compound, hyperserotonergia and such.

There are a couple of old preclinical human studies from the 1950s on this one, but all they describe is that it is less potent as a peripheral stimulant and anorectic than amphetamine itself. The 3-methyl analogue had a little more potency than this one as an anorectic, but it was still was an order of magnitude less potent than racemic amphetamine. Not that I encourage testing this one at the sort of dose that would be required to tell if it has empathogenic effects (until we know the 5-HT2B/MAOI activity), but has anyone out there ever tried it?

 

[Rectify]

This topic has already been discussed, so I'll just relay the information:

Yes, 4-methylamphetamine is reported to be entactogenic, and the high is said to be desirable but mental problems go with it.

4-ethylamphetamine is said to be the "best" of the
4-akyl-amphetamine series and is said to be without the 4-Me's nasty psychiatric side effects. Those side effects probably arise from the following metabolic oxidative pathway:

4-methylamphetamine --> 4-CH2OH-amp. --> 4-(C=O)-H-amp. --> 4-CO2H-amp

Kind of like how DOM can be problematic whereas DOET is more likely to be called 'lovely' at the correct dose. Personally, I think adding a 3-MeO group to any of that series would be a step in the right direction.

 

[Riemann Zeta]

^^ I realize that there have some mumblings and grumblings here and there, but I've not some across any definitive, detailed reports (and certainly no biochemical data other than the monoaminergic ratio profile). This reports that you refer to--what was the dose (just curious, I would bet around 50-75mg based on the in vitro numbers)?

What do you mean by 'mental problems' and 'psychiatric side effects?' Issues such as mania? Is it likely to inspire one to don the tinfoil hat? I have heard that DOM has a higher probability of causing manic reactions than other psychedelic amphetamines. But here we are not considering a psychedelic amphetamine. Without the 2,5-dimethoxy substitution pattern, there will be little appreciable 5-HT2A activity. 4-MeAmp might have some activity at the trace amine 1 receptor, but that could only be a good thing for anxiolytic/empathogenic effect.

Also, I would think that 3-hydroxy-4-methylamphetamine would be the most likely ring-activated metabolite. My bet is that DOM gets metabolized into a mixture of the 2- or 5-desmethyl analogues and the oxidized 4-methyl --> acid product, with the later being a result of the fact that the ring is already too substituted to easily add to.

 

[nuke]

The common human metabolites of DOM and their pathways are located in this paper:

Designer drug 2,5-dimethoxy-4-methyl-amphetamine (DOM, STP): Involvement of the cytochrome P450 isoenzymes in formation of its main metabolite and detection of the latter in rat urine as proof of a drug intake using gas chromatography–mass spectrometry

Andreas H. Ewalda, Michael Puetzb and Hans H. Maurera, ,
aDepartment of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Kirrberger Strasse 1, D-66421 Homburg (Saar), Germany
bBundeskriminalamt, KT 34-Forensic Toxicology, D-65173 Wiesbaden, Germany


Received 25 October 2007; accepted 29 November 2007. Available online 8 December 2007.

The designer drug 2,5-dimethoxy-4-methyl-amphetamine (DOM, STP) is known to be extensively metabolized in various species. The current study showed that cytochrome P450 2D6 was the only isoenzyme involved in formation of the main metabolite hydroxy DOM. In addition, the authors’ systematic toxicological analysis (STA) procedure using full-scan GC–MS was suitable to prove an intake of a common drug users’ dose of DOM by detection of hydroxy DOM in rat urine. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of DOM in human urine. However, DOM and/or other metabolites such as deamino-oxo-hydroxy DOM might be the target analyte in urine of CYP2D6 poor metabolizers.

Keywords: 2,5-Dimethoxy-4-methyl-amphetamine; DOM; STP; Designer drug; GC–MS; CYP2D6

http://dx.doi.org/10.1016/j.jchromb.2007.11.042

You may read the author's dissertation here:
http://scidok.sulb.uni-saarland.de/volltexte/2008/1972/pdf/AEwald_Diss_Final_nach_Kolloquium.pdf

 

[Erny]

Yes it is, em, interesting shit, and is very MDMA-like. We've already discussed it somewhere around here. It is known in Russia and Ukraine but is not very common, possibly also in Baltic states though I am not aware of the situation there. Known as p-TAP (p-toluaminopropane) or 4-MA. It is also one of the very few psychoactive chemicals I am really afraid of. After getting to know it, I feel it made me a different person. The changes are very light but I don't like them. It is notably dopaminergic, not very stimulating, but quite reinforcing, and may produce stereotyped behavior like amphetamine. It lasts 4 hours. As to oral activity, different people fall in two distinct groups: one either need 100-150 or 200-300 mg for full effects. Some people even state it is not very active orally, though effective upon insufflation or i/m injection. It is not a potent MAOI.

If you'll get some, never take more than a single dose in one day. Repeated dosing will quickly bring up very drastic after-effects with a clear picture of serotonin depletion like disturbed sleep, mood and cognition.

If what I wrote is not enough, feel free to ask.

 

[nuke]

4-methylamphetamine should be a nearly perfect MDMA-like compound, with an EC50s for [3H]DA and [3H]5-HT release of 44.1 nM and 53.4 nM, respectively (Rothman & Baumann, 2006)

Or quite an excellent neurotoxin, as Erny seems to be insinuating.

 

[Riemann Zeta]

Why do you say that, nuke? Simply because a compound functions as a monoamine releaser does not mean that it is ipso facto neurotoxic. MDA/MDMA's neurotoxicity appears to be a special case, chiefly related to its metabolites. Now, since dopamine also has that unfortunate 3,4-dihydroxy structure, anything that causes a lot of dopamine release has the potential to be neurotoxic if taken in very high doses for chronic duration...a la methamphetamine. But in low doses, I see no reason why it would be too dangerous, just because of a little released dopamine and 5-HT.

 

[nuke]

The compounds with release of both 5HT and DA or NE and poor MAO inhibition seem to be the problem. You have methamphetamine, diethylpropion, p-Chloroamphetamine, p-Iodoamphetamine and p-Bromoamphetamine all as toxins... An instance of a non-neurotoxic amphetamine releasing agent might be 4-methylthioamphetamine:

p-Methylthioamphetamine (MTA), was compared to p-chloroamphetamine (PCA) in a number of pharmacological assays. MTA was about 2-fold more potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and about 7-fold and 10-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]dopamine and [3H]norepinephrine, respectively. In drug discrimination assays, MTA was nearly equipotent to PCA in animals trained to discriminate saline from 3,4-methylenedioxymethamphetamine (MDMA), or two related analogues S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-MBDB) or 5-methoxy-6-methyl-2-aminoindan (MMAI). MTA caused dose-dependent increases of tritium efflux from superfused rat frontal cortex slices preloaded with [3H]5-HT, comparable to that induced by an equal molar concentration of PCA. The potential neurotoxicity of MTA was examined by measuring monoamine and metabolite levels at one week following an acute dose. A 10 mg/kg dose of PCA caused a 70-90% decrease of cortical, hippocampal and striatal 5-HT and 5-hydoxyindoleacetic acid (5-HIAA) levels, while twice the molar dose of MTA (21.3 mg/kg) had no effect. Thus, MTA is a potent, selective, serotonin releaser, apparently devoid of serotonin neurotoxic effects. This work also supports the idea that catecholamine systems may play a critical role in the neurotoxicity of PCA-like compounds.

http://www.erowid.org/references/refs_view.php?ID=7179

You also likely have the MAO properties of 4-MTA likely contributing to its 'lack' of toxicity.

As you can see, it has quite a reduced affinity for DA as compared to 5HT. However with the 4-methyl you are substituting a group with comparable electronegativity to the heavier halogens, which may be asking for trouble as we already know that these compounds are very strong serotonin depleting neurotoxins.

This would make sense. With lots of serotonin release, you would have elevated body temperatures, and with lots of dopamine release, you would have elevated peroxide formation. This is what's seen with most of the amphetamine neurotoxins, from which things like highly toxic ring-hydroxylated/amino acid-subtituted amphetamine/dopamine metabolites are formed after which mitochondrial destruction results.

 

[Erny]

Why?

I don't know what else should I say so that it could become clear that the best idea so far is to avoid this thing. Maybe I should explain it more accurately.

MDMA, MDA and MDE have their drawbacks, but will not get you into trouble unless taken daily or for a very long time. IAP (indanylamphetamine) is maybe not the most brilliant entactogen, but won't hurt you. They're also not too dopaminergic, this is true. This thing (4-methylamphetamine) has the destructive potential of almost the same order as that of cocaine, together with being far more neurotoxic than any of the above. I have nothing to prove the latter, but am sure. Something that is exactly opposite to what you have expected, right?

Theoretical speculations, especially non-professional, like those here at BL, are most often useless and futile in attempts to discern new drugs with desirable properties without practical knowledge. Though I think I've got an example to illustrate the opposite side: wandering around without proper knowledge is a bit dangerous. I know about two different people who took 4-bromoamphetamine not knowing it's a neurotoxin. It does basically the same things, an experince that is mostly similar to MDMA/amphetamine, followed by disturbances of sleep, mood and cognition that can last up to half a year. 4-methylamphetamine doesn't get close to that level of horror, but where it does is still worrifying at the very least. Not even the 5-HT depletion such things are caused by is worrifying, but rather some things that follow it. It will hit your memory and skills up to that you could even need to relearn something, your motivation, intentionality and prudence. First two are but a grid of interneuronic connections, mostly axons and dendrites that can regenerate, not necessarily cell bodies. Three last are where the center of your identity is, the frontal lobes.

 

[dorothyperkins]

And your ability to write coherent sentences? Sorry! I'm curious as to what you mean by that last bit but don't understand. I've tried this a couple of times, though only at low (~15 mg) doses, which weren't particularly interesting.

 

[nuke]

Go easy on Erny, I'm pretty sure he has English as a second language.