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Stimulants of the Future

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Stimulants Of Ahe Future Are Already Here

While perusing some of the posts, I came upon this one and decided that I needed to chime in here. While there are certainly more than two classifications of non-entactogenic stimulants that are drugs of abuse in animal models --and yes that is important because you find individuals who abuse strange atypical drugs that very few people find pleasant-- let's just narrow it down for simplicity's sake and say that abusable stimulants basically fall into two classes based on their interactions with the DAT and the VMAT-2, and whether they have any direct activity themselves at the D2/D3/D4 receptor subtypes: stimulants of the cocaine type and stimulants of the amphetamine type.

Now of the stimulants of the cocaine type, some of the most pleasant compounds ever created have been around for decades, but are relatively complicated to produce due to their extensive chirality, so veritably a handful of drug users have ever tried them and the vast majority of drug users have not even heard of them. These include WIN 35,065-2; WIN 35,428, RTI-121 and RTI-55. Of these, IME, There is no God but WIN 35,065-2 (let's call the others demi-gods.) Also note that none of these drugs lasts incredibly long, with some of them lasting perhaps three times as long as cocaine, but when the drugs last much longer, they tend to lose some of their euphoriant effect. I am not sure that this is absolute with cocaine analogues, but it does not seem to apply to amphetamine analogues: they can last for days.

If you look at the images in the Word doc, you will see all these cocaine analogues are phenyltropanes, but there are some very good analogues made from arecoline which substitutes the ubiquitous piperidine structure (which does appear on tropane if looked at in 3 dimensions.)

As far as amphetamine analogues, I have far less experience with these, but I do find 4MA (4-methyl-aminorex aka Euphoria) very pleasant along with derivatives of nomifensine and aminopropylferrocene . They are very pleasant but they still do not have the magic of cocaine type to me. Great amphetamine analogues that were not created by Sasha Shulgin (or at least synthesized by him) and are not entactogenic are difficult to come across. Most analogues are of lesser abuse potential than methamphetamine. If Shulgin had worked on cocaine analogues, I am sure we would have the equivalent of PIHKAL (Perhaps CAIHKAL. I have commented in the past on writing OIHKAL insofar as a definitive book on opioids, but it would be much more destructive, particularly with the way I tend to look at drug use lately. (i.e., I do not want anyone to die from a book like this which is why I doubt I would write one.)

If any of these compounds ever became widespread and easy to obtain, we would have "epidemics" far greater than the so called meth or crack epidemics (Both aminorex derivatives and cocaine analogues would easily change most stimulant addicts drug of choice, of that I am certain, as I never did these drugs with anyone who did not start to nag me about doing more. I quickly learned to be careful who you share with. If they don't have respect for you, they will try to obtain these drugs at all costs. I know the drug in part has a hand, but the character is also an issue.

MobiusDick
 

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aminopropylferrocene, not only a stimulant but full of ferric goodness, mobius is this cyclopentadienyl iron compound what you mean, if so I am truly fascinated. tell me more.

most of the phenyl tropanes seem not to have too much potential. on the whole they are slow on long duration materials, though there are a few like troparil that mobius mentioned which are devastatingly effective, and a few ester and para substituted on the phenyl variants which have extreme speed of onset, better than cocaine with very effective DA raising abilities.
 
^ Fe(cp)2 compounds seem to be toxic for cells?
(interupt dna replication by joining two ends and blocking it from more replicating)
 
Cocaine analogues.

According to Rhodium, the (-)-2-beta-carbomethoxy-3-beta-(3',4'-dichlorophenyl)-tropane analogue was shown to be most addictive / reinforcing in animal studies.

Interestingly, the DEA deleted the study's experimental procedure section!

About Nomifensine Analogues

I had never heard of this compound or seen its structure until just now, but I immediately wondered when I saw it what removing the anilinobenzo group would do.

So is N-methyl-3-phenylpiperidine a known nomifensine analogue and have you tried it?
Even more interesting to investigate to me would be the activity of N-methyl-3-(3,4-methylenedioxyphenyl)-piperidine.

Sorry if all this dopamine-mimicking, phenethylamine talk bores you, vecktor, it's what I like.
:)
 
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I am not averse to stimulants, and I think the phenyl tropanes are very interesting as are fencamfamine and nomifensine. The phenyl tropanes are tedious to make unless one starts with cocaine and that defeats any legal advantage they have. RTI-55 p-iodophenyl methoxy carbonyl tropane has been tasted in man, and was not found to be particularly interesting or worthwhile.

I am just bored with people just doing minor tweaks to known pea and tryptamine molecules and then thinking that it has never been thought of before, it has.............on numerous occasions.

nomifensine has problems due to immune system reaction to it followed by hemolytic anemia, look up merital, hoechst. it appears that problems had emerged in trials but were ignored, though somehow hoechst didn't get sued out of existence over it. All the evidence points to the mechanism of the toxicity being to do with the aniline moety stabilising the metabolically oxidised tetrahydroquinloline, i have posted about it on this forum.
the substance without the aniline part would be N-methyl 3-phenyl piperidine, for some reason I do not like the look of this molecule, though it seems unlikely it will metabolically oxidise to a stable tetrahydyropyridine, the stabilising phenyl is in the wrong position, I just don't like the look of it- gut instinct I guess.

the related substance diclofensine made it some way through trials before being stopped, sometime in the early 80's. It appeared as a research compound through legitimate channels for a while. diclofensine is one of the most effective substances at increasing extracellular dopamine levels through it is supposed DAT inhibition, and it also is very effective at inducing stereotypical behavior in rats.
next to nothing is known about its effects in man.
 
vecktor said:
next to nothing is known about its effects in man.

That's not totally true;

Double-blind comparison of diclofensine with nomifensine in outpatients with dysphoric mood.

Funke HJ, Holtmann W, Ismail S, Jansen W, Leonhardt KF, Muth H, Omer LM, O'Connolly M, Ramm H

Depressed outpatients (n = 107, age 26-75 years) were treated with either a 50 mg single morning dose of diclofensine (n = 54) or 75-100 mg nomifensine given in two divided doses (n = 53) over a period of three weeks. The baseline mean values of the Depression Status Inventory (DSI index) of Zung corresponded to those of a mildly depressed population, as given by Zung. At the end of the treatment the mean DSI and Anxiety Status Inventory (ASI-index) values of both groups dropped to the levels of a normal population. The side-effect profile of the two treatments was similar. There were no side-effects indicating sedation. Adverse effects of the anticholinergic type were rare. It can be concluded that both diclofensine and nomifensine are beneficial for the treatment of depressed outpatients and that in a dose relation of 2:3 (diclofensine:nomifensine) they lead to a similar improvement in depressive outpatients.

PMID: 3725890

Long term toxicity is still a big issue with this one, though.
 
Win 35,065-2.

At 9,000 euros a gram, I don't seen Troparil aka WIN 35,065-2 aka
(-)-2-beta-carbomethoxy-3-beta-phenyltropane becoming a widespread drug of abuse on the illicit or semi-illicit markets anytime soon.
 
<pyridinyl_30> said:
About Nomifensine Analogues

I was prescribed nomifensine as antidepressant when it was still on the market. It had little if any effect and certainly was not recreational.
 
And not to forget: Indatraline, yet another potent DARI without recreational value.
 
I didn't mean to imply that WIN 35,065-2 (3-beta-des-OC(O)-cocaine) doesn't have great abuse potential as has been reported but rather that is exorbitantly expensive when compared with other, similar drugs such as freebase cocaine, for instance.

Of course, all of that could change instantly with the discover of a simpler, better, cheaper, easier and/or more elegant synthetic route leading to Troparil starting with atropine or some other inexpensive plant alkaloid and common industrial and/or over the counter reagents.

I wonder what the dosage range and estimated lethal dose 50 percent (LD50; a drug safety measure) for humans of this compound is?
 
The chemistry of these compounds has been very well researched. There won't be no miraculous new route bringing down the price to an affordable range. Either you start with cocaine as precursor, or you make the precursor, but then you end up with a mix of isomers.

I don't think the tropanes are chemically/economically suitable for the RC market. Better look for dopamine reuptake inhibitors from other chemical classes.
 
Nomifensin has the following Ki values for uptake in nM: DA 79, NE 3.8, 5-HT 874; diclofensin DA 14.6, NE 4.4; 5-HT 18.8; indatralin DA 0.99, NE 0.26, 5-HT 0.48. The indatraline values are from a different study, so might not be directly comparable. Not sure if anybody is interested in that, but I post it anyhow.
 
As BZP surrogates I would suggest the following:
1-(2-Pyridylmethyl)-piperazine
1-(3-Pyridylmethyl)-piperazine
1-(4-Pyridylmethyl)-piperazine
Some might even be commercially available, else they are easy enough to make. Replacing the aromatic ring with a 2- or 3-thienyl would be a further option. All that is just classic medicinal chemistry. Desoxypipradol with either one (best) or both (slightly less potent) phenyls replaced by 2-thienyl is still a potent stimulant. The corresponding thienyl-pipradrols (with OH) are only weakly active. So there's some unpredictibility in the SAR of these compounds.
 
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I've never even heard of this 'aminopropylferrocene' compound that is purported to be a stimulant. Moreover, I don't really understand the chemistry of it: an organometallic ligand coordinated with Fe? Not only does that sound like trouble for human cells, it also sounds like a highly improbable structure for a stimulant.

Ferrocenes are used as a catalysts and molecular scaffolds in organic reactions, but I have never heard of one used as a pharmaceutical. Is this the actual structure? If it is, I think it would be mad toxic.
 

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I supposed that it just link to one cyclopentadienyl ring, not linked to both two.

Personally i think adding ferrocene doesnt attract me that much due to the fact that sandwich compounds tends to be cell destroying. (crosslink on DNA strands)
 
<pyridinyl_30> said:
bk-2-benzylpiperidine
So many drugs, so few resources.
Don't know what the bk stands for, but 2-benzylpiperidine has been scientifically tested and found to be a very weak DA reuptake inhibitor (IC50 8.8 µM). It was also practically inactive at the other uptake sites.
 
I would love to see new stimulant come out that relases serotonin and dopamine like the way meth does
in Depot form tablets that start from 100% relase decreasing each day in 7 days and you'd get no come down at all.
Wouldnt hurt if it relased all serotonin the way mdma does, but kept the high going on for as long as you wanted..

For what purposes it'd be created? Happines.. but thats not possible becuz it would destroy your brain in matter of months, in reality.

WTF Im talking about? Gotta go bed now.
 
^A compound with similar properties to your pill has been created:N-methylindatraline: Slow-Onset, Long-Duration 3-(3',4'-Dichlorophenyl)-1-indanamine Monoamine Reuptake Blockers as Potential Medications To Treat Cocaine Abuse. J. Med. Chem. 2000, 43, 4981-4992. A high dose will last several days. The lasting stimulantion and lack of sleep might not be too good for your mental health.
 
A high dose will last several days. The lasting stimulantion and lack of sleep might not be too good for your mental health.
Can't sleep...clown will eat me.

I only take long-acting stimulants (or extended release versions), but whoa, a half-life of several days--that's insanity (literally, at least once you've been awake that long). But I doubt that any of the indatralines are all that stimulating.
 
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