Stimulants of the Future

Well, my other thread, "Possible Drugs of the Future" turned into mainly a discussion about opioids, mainly the most potent ones...and I must say, it's extremely informative and interesting. But unfortunately, all the other classes of drugs seem to have been looked over.

So, what about stimulants of the future? Are various analogues of amphetamines or other stimulants possible? Could these are qualities that make them more desirable than say cocaine or methamphetamine? Even if it's completely theoretical (and unrealistic or would never happen), I'd still like to hear.

Say some type of cocaine analogue (that wouldn't be made due to complexity and it's simpler to just make cocaine from Coca plant) that had even greater euphoria and/or longer duration (say 1-4 hours instead of like 30-45 minutes, depending on person, metabolism, etc.)?

Same goes for methamphetamine. Any possible amphetamine derived drugs with more euphoria than meth (say an amphetamine or amphetamine like drug with the euphoria of cocaine; I find coke to be more "euphoric" than amphetamines although I know this is subjective)?

And again, same goes for other stimulant-like drugs. Any way to make some drug similar to Modafinil (sp?) with euphoric properties desirable by stimulant fans?

Lastly, what about a more potent, more euphoric ecstacy (or any MDxx)-like drug? This one is of particular interest to me.

With any of these, I'd appreciate if you could include "possible drugs" that are more euphoric (may be hard to tell since no one has personal experience), more potent, varying durations of action, or even lower side effect and risks?

Hopefully, you geniuses can go as nuts with this one as you did with the other post and all the great information about opioids? Thanks in advance for what I know with be some great responses.

I can't foresee any cocaine derivatives being introduced because, as you've already mentioned, it's so much cheaper to just grow the stuff than to synthesize it. Even having a longer duration wouldn't necessarily make it more popular, since generally if people are bothered by cocaine's short duration, they'll switch over to amphetamines.

As for amphetamines, there are hundreds of modifications that can be made to the amphetamine (and related phenethylamine) molecules which are active. Most of these drugs, however, are psychedelic in nature (ie DOM, DOB, Aleph), and are recounted in PiHKAL.

With opiates, what allows people to create more potent analogues is that minor modifications can allow better absorbtion/solubility and can cross the BBB better without affecting their method of action (ie they're all still mu-agonists). With amphetamines, the same is true regarding the difference between amphetamine and methamphetamine, but once you get past that minor modification, further changes tend to alter their method of action, increasing serotonergic activity and becoming more psychedelic. This is a bit of a generalization, since each individual drug is different, but that's the general story.

Now, there are some interesting non-amphetamine substances that have similar effects, like methylphenidate (Rritalin), atomoxetine (Strattera), and Bupropion (Wellbutrin, Zyban). All three of these substances will increase synaptic dopamine and norepinephrine levels, much as amphetamine will, but are not generally considered to be recreational. Most of the research into amphetamines tends to be either pharmaceutical companies researching ADHD medications that won't be abused or redirected to the black market, or people like Sasha Shulgin researching the various variations on the phenethylamine/amphetamine structure to produce new and different psychedelic compounds.

As for more potent MDxx drugs, I know Shulgin lists a few in PiHKAL, but as far as I know, none of them were quite the chemical that MDMA was. The thing with MDMA is that is has some very unique effects, almost a cross between an amphetamine and an SSRI, and part of its popularity is due to the fact that it's not overly powerful (compared to other psychedelic phenethylamines). Obviously you've probably heard of MDA and MDEA, so there are some possibly alterations that can be done, but neither drug really hits the "sweet spot" that MDMA does in terms of recreational effects.

Well, my other thread, "Possible Drugs of the Future" turned into mainly a discussion about opioids, mainly the most potent ones...and I must say, it's extremely informative and interesting. But unfortunately, all the other classes of drugs seem to have been looked over.

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you said:

P.S. If you feel like mentioning other "mind altering" drugs in development, feel free, but please try to keep it to opioids.

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you make a thread asking people to please keep the discussion to opioids and then complain that "all the other classes of drugs seem to have been looked over."? that makes absolutely no sense to me.

/me visits a philip k. dick -esque amphetamine vending machine. cant remember what short story that was from in particular sorry....

i think that drugs of the future will actually be cocktails designed to increase specificity to certain pathways. there are SO MANY signalling proteins that are regionally expressed and that alter the activity of GPCR's, g-proteins, adenylyl cyclases etc. etc.
once we work a few more of them out we'll be able to give really low doses of drug and still acheive the desired effects with few or none of the side effects.

Stimulants I think are one thing that people could hold out some hope for a new, plant derived drug. The monoamine transporters are so promiscuous, it seems all you need is a benzene and a nitrogen somewhere... and your in.

cannabis, yeah, I forgot I added that part in other thread...that makes a lot more sense now. sorry for the confusion.

Hyperion, we both know synthesizing cocaine is basically pointless. But hypothetical speaking, what could be done to modify cocaine (if someone had a lot of free time on their hands)?

I'm not a chemist, so I don't really know what modifications could be made. I do know that some have been made, which is how we have procaine (novocaine), lidocaine, and benzocaine. In all three cases, the psychoactive effects of cocaine are completely missing, and these drugs instead act purely as topical anaesthetics. Someone else will have to explain why this is so. The thing is, I don't believe that any of these other -caine drugs are as effective as cocaine for topical anaesthesia anyways, given that cocaine is still used as a topical anaesthetic in some surgeries (including, of all things, nasal surgeries). Unfortunately, I can't seem to find an image of any of these non-psychoactive cocaine derivatives to compare to the cocaine molecule to see where the differences are, otherwise I might have some ideas. Anyone?

Well, cocaine itself is indeed a pointless waste of money. However, it will always be popular among the wealthy as it is a way of advertising one's vast disposable income. There are a number of modifications to cocaine that have become popular as radioligands to highlight DAT proteins in PET/SPECT scans. For example, the WIN 35xxx and RTI series of compounds are tropanes with various non-ester aryl moieties replacing the benzyl ester of cocaine. RTI-55, for example, is 3-(para-iodophenyl)-tropane-2-carboxymethyl ester and is used with radiolabeled I to trace DA and 5-HT transporters. It has a duration that is at least 20x that of cocaine. However, tropanes are a bitch to synthesize, so I don't think that these compounds will ever become popular.

In terms of reuptake inhibitors, I think that methylphenidate will become even more popular in the future. However, I doubt that instant-release methylphenidate will still be available or even allowed. I am sure that all methylphenidate available will be unsnortable, uninjectable, wax-matrix polymer bead based extended release tablets (to prevent "abuse"). In addition, I can see all scheduled medication in the US and UK having RFID police alerting chips in each pill, so authorities can randomly scan peoples' flats, cars, clothing, etc...for stockpiled pills. Also, as I mentioned in the 'Drugs of the Future' thread, ephedrine will be scheduled soon in the US, leading to the demise of methamphetamine as a street drug and the reintroduction of (dl)-amphetamine sulfate from organized crime syndicates in former Soviet nations. This, of couse, means the US and UK governments will overreact with a barrage of cruel, vindictive and Orwellian legislation (more-so in the US than in the UK, due to the religiosity of the jesusland freaks). However, I believe amphetamine proper will never die completely in streets of the US, no matter how many ridiculous laws, obscenely lengthy prison terms and mandatory execution policies are enacted.

As for future stimulants themselves, I believe that modafinil derivatives are where it's at for the future. Since modafinil has nill abuse potential and future derivatives of it will have even less, I think that is where pharmaceutical companies are headed. I think the development of stimulants for ADHD is over, doctors in the EU will not prescribe stimulants right now, period, and doctors in the US have the DEA crawling up their asses, threatening their medical license with every script for Adderall or Dexedrine they give out. The only new ADHD medications will extremely targeted molecules that work on various cellular protein cascades and carry zero abuse potential and thus do nothing to promote wakefulness or alertness in individuals without ADHD.

In short, all psychopharmaceutical drugs of the future will not be anything that people want to take, only something that people have to take. They will be neither dysphoric nor euphoric, they will simply be extremely targeted and relatively side-effect free.

Interestingly, this will lead to legitimate (or, more properly, former legitimate scientists) going 'underground' as clandestine chemists and researchers. Fueled by organized crime money, these will not be Bill-bob and Bubba blowing up the hick-town trailer park while trying to synthesize methamphetamine. Instead, these will be serious pharmacologists and chemists (likely PhDs and advanced grad students) that are sick of the paucity of funding, squalid lifestyle and restrictive, bureaucratic red-tape that academia brings.

I'm surprised nobody has mentioned phenmetrazine...

Phenmetrazine is too hard to synthesize. It requires nor-ephedrine, which was banned in 2000. Same goes for 4-methylaminorex (4-MAX), which is why both are as rare as it gets in the drug world.

Was phenmetrazine part of the phen/fen weight loss combo? If so, i didn't think it had much euphoria?

Phen-fen was phentermine and fenfluramine, I believe.

Fenfluramine is an interesting one...in theory is it an almost purely serotonergic amphetamine. I would bet that fenfluramine + dextroamphetamine feels a lot like MDMA.

http://mdma.net/misc/fenfluramine.html

MDMA vs. Fenfluramine

I have a prescription for phenDImetrazine (phenmetrazine with an extra N-methyl group). Phendimetrazine is metabolized by the body, according to my Physician's Desk Reference, to phenmetrazine and phenmetrazine N-oxide. While I enjoy my monthly phendimetrazine fix, it does not compare to methamphetamine. Neither does Ritalin (methylphenidate) or Adderall (amphetamine).

I think clear, recrystallized, nearly pure dl-methamphetamine hydrochloride is probably going to remain king of the stimulants for some time. Its synthesis is easy, it is chemically synthesized from a naturally occurring alkaloid derived from the Chinese ma huang plant, the quality of its high is very good, and the high lasts a long time. However, I would like to try the heretofore unscheduled 2-benzylpiperidine, a methylphenidate analogue designed to have a much longer half life than methylphenidate, as a possible stimulant.

Cocaine doesn't last long enough for me, is too expensive, and has agonizing come downs. Plus, the first thing many people do after doing some cocaine is have to take a nasty shit while they are high. Sure, some cocaine analogues may be very powerful, but they will always be extremely expensive to synthesize as long as they rely on cocaine as their starting material. As for the entactogens, I don't think MDMA / MDA can be beaten either, even though I am on methylone (that is, MDMCAT) right now. OTOH, I would like to try 3,4-dichloromethamphetamine.

Caffeine and nicotine, two legal stimulants, will probably also continue to be used extensively in the future. Speaking of nicotinic agonists, I would also like to try ABT-594.

Modafinil and ephedrine are crap drugs in my opinion.

Dope_User: The abstract that your link leads to is by Ricaurte, et al. I don't trust that bloke as far as I could throw him--he was the one using 150mg+ doses of methampetamine instead of MDMA "by mistake" and was forced to recall his paper in Science, right?

Oh, and phenDImetrazine is quite fun. I took some (315 mg, sustained-release) a long time ago when visiting a friend in NYC--we went clubbing and were out until 4 or 5 am. I thought it was a nice feeling, kind of like pure (d)-amphetamine, with no heart palpitations or anything similar. It did take a long time to kick in, however. At the time, I assumed it was because the phendimetrazine had to be converted to the first-pass N-desmethyl metabolic product in vivo, using the P450 2D6 enzyme. Reading a review by Rothman, et al (2003), I found out I was right--phendimetrazine is just a prodrug for phenmetrazine. However, while it was fun for a night, I would never take it chronically for ADD, due to the dangers of primary pulmonary hypertension (a risk with all amphetamines, more pronounced with some of the noradrenergic anorectics).

As for some stimulants/nootropics of the future, here is a little list I have compiled:

Nicotinic Agonists:

ABT-594 (5-(azetidin-2-yloxy)-2-chloropyridine)
Conitine (alpha-keto-oxidized nicotine metabolite)

AMPAKines:

Pramiracetam (out now in the EU, very $$$) & congeners
CX516
CX614 (2H,3H,6aH-pyrrolidino[2",1"-3',2']1,3-oxazino[6',5'-5,4]benzo[e]1,4-dioxan-10-one)
Other Cortex Pharm. Derivatives

Ring-Closed Amphetamines:

2-benzylaziridine
2-benzylazetidine
2-benzylpiperidine
3,4-dichloro-methylphenidate
ethylphenidate
N3-methyl-4-methylaminorex
3-methyl-(1-phenylcyclobutyl)butanamine
N-ethylcathinone

Modafinil Derivatives:

4,4'-dichloromodafinil
pirisudanol (3-hydroxy-2-methyl-5-((4-(2-(methylamino)ethoxy)-4-oxobutanoyloxy)methyl)isonicotinic acid)

The last one is a particularly odd drug. It was around in the EU for a while, as a stimulating antidepressant, like bupropion and adrafinil, but I can't find ANY info on it, not even any old journal articles.

Riemann Zeta, sorry you didn't find that link to be all that credible. I simply stubbled across it when searching for anything I could find comparing MDMA to fenfluramine because you have mentioned fenfluramine + dextroamphetamine may feel similar to MDMA. I must admit, I couldn't tell you the first thing about what scientists/researchers are credible or not...but this new forum is helping.

I would like to hear more about the comparison you made between fen. +d-amp. and MDMA though. You said fen. is an "almost purely serotonergic amphetamine" and that sparked my curiousity. Although, I find it somewhat hard to believe that fen. + any amp. could feel similar to MDMA...do you have any info. (other than speculation) about this? Also, are there any other mainly "serotonegic"amps. (other than those mentioned) that are more potent (in terms of serotonin agonism, release, reuptake inhibition)? To everyone, what are you opinions on amps. that act strongly on serotonin? Do these have the potential to be euphoric amps., possibly with some slight hallucinogenic properties (similar to MDMA)?

Riemann Zeta, you also mentioned a couple Modafinil derivatines. You said prisudandol was prescirbed as a "stimulating antidepressant" and I'm assuming it probably doesn't have much (if any) potential for abuse. But what about other modafinil derivatives (or derivatives or drugs in the same class)? Does anyone think such a drug could be synthesized that would be euphoric (such as the first derivative R.Z. mentioned; 4,4;-dichloromodafinil)?

NOTE: I just did a search for pirisundandol and found info. on "pirisundanol." I haven't read anything on it yet, but maybe you had a misspelling and that's why you couldn't find any info.

You are correct, it was a typo, the name is Pirisudanol. The compound goes by a number of names, I am not even sure if 'pirisudanol' is the correct one; I have also heard it called pyrisuccideanol. I remember one of the trade names for it was 'Nadex,' but it hasn't been around for a long time.

Here is a link for the structure: http://www.psychotropics.dk/usr_vie...Alphabetical+index&historyline=&Catalogtype=A

As for fenfluramine: well, MDMA seems to release NA, DA and 5-HT. Dextrofenfluramine only releases 5-HT, whereas dextroamphetamine releases NA and DA. But MDxA (especially MDA) compounds also have affinity for the 5-HT2a receptor, which might contribute to their 'trippiness.' MDEA ('Eve') is more 5-HT selective than MDMA or MDA, so it might make a better comparison.