Stimulants NEW Pure Dopaminergic stimulant: Alpha-cyclopropyl-amphetamine!!! 🤓

[LikeADaVinci]

hi,

I’m interested in finding and experimenting with a purely dopaminergic releasing amphetamine drug, as it seems EVERY STIMULANT DRUG OF THE AMPHETAMINE CLASS RELEASES BOTH NOREPINEPHRINE AND DOPAMINE BOTH, (or rarely serotonin and dopamine (cyclazodone)), but that purely dopaminergic releasing agents or reuptake inhibitors are unknown …

So take UWA-101 for example, which is MDMA with an alpha-cyclopropyl moiety as opposed to the standard alpha methyl … this drug drops the activity at the NE receptor down to nothing while retaining the serotonergic activity (classic to methyenedioxy amphetamines) while causing a huge boost in dopaminergic affinity (something largely spared by MDMA naturally)

So the logic goes: what if we drop the methyenedioxy bridge in UWA-101 and demethylate the nitrogen (so it’s not neurotoxic) and simply have alpha-cyclopropyl-dextroamphetamine?

This can easily be made similar to PN2P with benzaldehyde and alpha-cyclopropylamine (I think?) to yield a precursor analguous to PN2P except with a cyclopeopyl moiety instead of methyl, that when reduced with sodium borohydride should yield the desired (R/S)-alpha-cyclopropyl-phenethylamine?

Going by structure activity logic, if the alpha cyclopropyl in UWA-101 vs MDMA drops the NE activity and drastically increased Dopaminergic activity, shouldn’t alpha-cyclopropylamphetamine follow suite and be a purely dopaminergic releasing agent with no NE (neuroepinephrine) receptor activity?

Wouldn’t that be the holy grail of amphetamines? No increase in blood pressure or heart rate (no strain on the cardiovascular system, no stress induced on the body) while offering purely pleasurable stimulation?

In thinking of synthesizing some and trying it out.

My only question is: is there any reason to think that methylcyclopropylamine wouldn’t bond with benzaldehyde at the mid-point carbon in between the amine and the cyclopropyl group?

Thanks!

If anyone else wants to help me out any synthesize this before I get a chance to (it will probably take me a year to find the time to complete this) could you please let me know of the result here on this thread or by PM?

Thanks!

Christopher Scott

 

[negrogesic]

Going by structure activity logic, if the alpha cyclopropyl in UWA-101 vs MDMA drops the NE activity and drastically increased Dopaminergic activity, shouldn’t alpha-cyclopropylamphetamine follow suite and be a purely dopaminergic releasing agent with no NE (neuroepinephrine) receptor activity?

Wouldn’t that be the holy grail of amphetamines? No increase in blood pressure or heart rate (no strain on the cardiovascular system, no stress induced on the body) while offering purely pleasurable stimulation?

Your underlying assumption is wrong. An amphetamine without ability to release norepinephrine wouldn't be the "holy grail of amphetamines". Norepinephrine (NE) release is important to the reinforcing effects of amphetamines, heightening arousal and alertness etc. Drugs that increase both dopamine and NE are generally more reinforcing than purely dopaminergic drugs, but this ratio (selectivity) is important. Overly selective dopamine releasers often have less reinforcing effects because they lack the full stimulant effects provided by NE release or reuptake.

As far as your proposed molecule (alpha-cyclopropylamphetamine) the overall bulkiness/steric hinderance of the cyclopropyl group would reduce the molecule’s ability to fit into the binding site of DAT as effectively as amphetamine/meth/aminorex etc. This would probably make it act more like a reuptake inhibitor, with the bulkiness causing it to block transporter reuptake, rather than promote release.

But again the underlying logic is flawed. An amphetamine analog that is purely dopaminergic would be less rewarding than one with ability to release NE. What the optimal rewarding DA:NE ratio is for releasing agents, I'm not sure. This optimal ratio has been better studied in reuptake inhibitors due to the massive amount of phenyltropanes created and the ability to fine tune DAT:NET:SERT selectivity in such reuptake inhibitors. Cocaine is near optimal, although there a few synthetic phenyltropanes that are supposedly more reinforcing in animal studies. The optimal ratio of DA:NE release might be something like methamphetamine or 4-MAR, but its hard to say because of the 5HT release factor with both those drugs, which of course changes the reinforcing properties (particularly euphoria). I've tried some quite selective dopamine reuptakers (like morphodrol) -- which when vaped had a very strong urge to redose despite producing marginal euphoria. That's why the lever pressing animal studies should be taken with a grain of salt, because some dopaminergic stimulants can be compulsively reinforcing, but not especially enjoyable.

Anyway alpha-cyclopropylamphetamine would be a crappy drug, and if anything it would likely be dopamine reuptake inhibitor given the constraints of the dopamine transporter.

Your whole premise of more dopamine = more fun is based on the simplistic view that society has on dopamine, whereby people think that dopamine = fun, but the reality is more complex than that. Why waste a year trying to figure out how to synthesize a drug based on that half-baked notion (especially given the lack of understanding of how ligands interact with the DAT, i.e., that adding a cyclopropyl group would actually turn it into a reuptake inhibitor, not a releasing agent).

This is why I presume you weren't actually planning on synthesizing this compound, because anyone capable of synthesizing such a thing would also have enough of a grasp on SAR to realize that it wouldn't even make sense to do so.

That said, some Chinese RC manufacturers have synthesized some pretty awful stuff just in an attempt to skirt the law. For instance, I was unfortunate enough to try 3F-PHP, which felt like a highly selective NE reuptaker. It was basically an anxiety attack in powder form.

 

[emkee_reinvented]

MDAI, very selective primarly for Serotonin.
A good name would be Serotonin Straightjacked.

Bit of balance is better.

 

[Skorpio]

Please don’t try to synthesize that compound. Your methods would not give you what you think (and if you have to ask, you probably shouldn’t be doing it).