I Like to Draw Pictures of Random Molecules

[Nagelfar]

^simple m-amp + MPH. But it begs the question, is β-Phenylmethamphetamine and related a DRI or a DRA? Anyone know?

phenmetrazine + the tropanesque cyclohexane

^just silliness. The "dimerization"-type product of that chromen-2-one functional cocaine analog with strobamine on the other side, because it's somewhat formed as it's inverse.

 

[Nagelfar]

I was thinking the thiambutenes may be a better match for a methylphenidate styled opioid than the fentanyl's, esp. after looking at that simple opioid dimethylaminopivalophenone:

^Are we getting closer? Any input/feedback on the above?

 

[Dresden]

Just because. And

PMEA

^--Hopefully/presumably less deadly than PM(M)A and, hopefully again, possibly bestowing a unique, smacky feeling.

^--Can't vouch for it first-hand, but heard second-hand (hearsay, I know) at the Hive to be a highly visual and rewarding psychedelic. N-methyl, N-ethyl, 3-chloro, and 3-iodo variations can be made as well. The same OP referred to the often deadly

PMA as a "crappy, ecstasy type drug."

Thinking 2,4-di-MeO-amphetamine is at least about as active as TMA-6, which isn't necessarily saying much of anything. Possibly stoning.

Can't read 2,6-di-MeO-amphetamine either way.

Would be surprised if 3,5-di-MeO-amphetamine did anything.

I have very low expectations for 2,3-di-MeO-amphetamine.

3,4-di-MeO-amphetamine has always looked great to me, but apparently you have to ingest half a gram or more to get many desirable effects such as visuals.

The trimethoxy amphetamines are well covered in PiHKAL. The dimethoxy amphetamines, not so much. Unfortunately, however, all methoxylated amphetamines are illegal here in the U.S. per the Controlled Substances Act (CSA).

Lidocaine inspired amphetamine.

 

[aced126]

Nagelfar, I posted your mph/amphetamine molecule a while a go. I expect it to have DRI properties only; it seems the carbomethoxy binding to a tyrosine residue in DAT gives DRI activity.

 

[Dresden]

Yeah, I did too. As for beta-carbomethoxy(meth)amphetamine's properties, it's impossible to be sure without making and testing it, which applies, I know, to pretty much all the molecules in this mega sticky thread.


* * *

I used to have high hopes for this one, a eugenol derived MDMA metabolite, but then heard somewhere it is only like 1/50th as good a neurotransmitter releaser as MDMA. Plus, I lost interest in it somewhat after trying and being disappointed in 3-MeO-MA. Come to find out today, it's an oxytocin and vasopressin releaser, so all hope is not necessarily lost on it after all.

I'm just calling this thing THE BEAST and the next one

THE BEAST, JUNIOR.

These last two are great research chemical fodder to skirt the new law in the U.S. anyway.

 

[roi]

 

[SKL]

^i'd try that, well, as long as someone else tried it first

 

[Dresden]

This has elements of both a dopamine reuptake inhibitor (a beta carbomethoxy group is present) and a 5-HT and DA releaser (mephedrone does both to the extreme), so I don't know which it would be. However, according to ebola?, all NT releasers are also reuptake inhibitors, but tbh, I don't know if that's true and, if so, if it means anything important. Aced126, a penny for your thoughts on that?

MEPHEDRATE

Since the carbomethoxy group is hydrolyzed to the carboxylic acid fairly quickly, the duration of this little gem is most likely (and probably thankfully) relatively short. I would expect it to last no longer than between 1 and 3 hours.

* * *

ENIGMA

ESTER-METH

Aspartame inspired (+)-N-methylacphetamine (the m for methyl immediately after the a for alpha has been replaced with a c for carbomethoxy). Cannot be easily made from L-phenylalanine, the naturally occurring isomer of phenylalanine!

* * *

"dizzy like this, dizzy like this, dizzy like this, dizzy like this, dizzy like this, dizzy like this, dizzy like this, dizzy like this"

 

[aced126]

It's going to be a releaser if 1) it is a substrate of the respective transporter, 2) it can dissociate from the transporter once inside the neuron, 3) it can release neurotransmitters from their vesicles and 4) it can trigger the transporter to reverse its function and transport neurotransmitters from the cytosol to the synaptic cleft.

All releasers will be reuptake inhibitors to an extent, because it will occupy the transporter for an amount of time, in which the endogenous neurotransmitter can't bind and be reuptaken. However, if the exogenous drug is reuptaken quickly, this time will be very short and so reuptake won't be blocked as much (given the transporter hasn't been reversed in function). Releasers also block reuptake by the fact that they make reuptaking transporters work in reverse, which in essence is blocking reuptake of the transporter as well as releasing more cytosolic neurotransmitters.

Good specific reuptake inhibitors will be substrates of the transporter but either 1) block the conformational change taking place in the transporter, or 2) dissociate to a lesser extent than releasers once exposed to the cytosol. I'd guess they satisfy 1) by causing sterice and/or electric hindrance and 2) by stronger binding interactions.

For the molecule above, is it likely to be a substrate of DAT and SERT? Yes.

Is it likely to cause much steric hindrance preventing the transporter from transporting? Maybe, like ritalin does

Is it likely to have problems dissociating from the transporter once exposed to the cytosol? Yes, like ritalin, because of the stronger interactions with TYR156 in DAT and TYR163 in SERT.

What role will the methyl group play? It will increase SERT affinity by causing stronger VDW binding interactions with the very lipophilic part of the active site of SERT. Overall though, not much cytosolic 5HT will be released and more will be released from natural vesicle release. SERT is likely to be blocked however. This might give the molecule SSRI properties.

Compare the molecule to 4-methylmethylphenidate. Not much acute serotonin activity at all. If you take it similar to an SSRI regime, one might expect antidepressant effects to start after a couple of weeks.

It should however be a good dopamine reuptaking inhibitor, the effects of which are much more easily observed acutely.

Tldr; like ritalin, a pure reuptaking inhibitor with maybe some SSRI properties as a result of this

 

[dopamimetic]

I'm thinking about the possibility of a fusion between an arylcyclohexylamine and an oxazoline-like stimulant e.g. MXE & 4-MAR.

I know that there have been proposed PCP analogues with a 5 instead of 6 chain ring -> now take this and combine... probability for it to actually work is next to none, but it would make some super-maniac-roflcoptr-rolling-neuroprotective RC in one molecule

 

[aced126]

Just take both at once?

On a different note, does anyone know that effect of a beta carbomethoxy group on binding to and interacting with different 5HT receptors?

 

[aced126]

Dresden, your ester meth molecule is very similar to O-methylphenylalanine and might well have been documented. Anyone know if this analogue of said amino acid has been made?

 

[Dresden]

Is O-methyl-phenyalanine active as a stimulant? Thanks for the info on mephedrate, too.

What about ENIGMA's projected pharmacology?

 

[aced126]

From what I know about the alpha methyl group, it is increases logP and may play a role in binding interactions but its main role is blocking oxidation at the alpha carbon. Phenethylamine is a very potent releaser of dopamine but its very short half life (~30 seconds) blunts its action. Now, about this compound, it is unlikely to be a good substrate at MAO, but it might be prone to demethylation at the ester which will terminate activity, and also it may lead to different electronic effects at the receptor. It might even cause a steric clash but then again prolintane is a good reuptake inhibitor.

 

[Dresden]

On a different note, does anyone know that effect of a beta carbomethoxy group on binding to and interacting with different 5HT receptors?

Looks like we have the same question. But yeah, the beta carbomethoxy will shorten enigma's half life dramatically in comparison to mescaline in all likelihood. I would expect its half life to be in the 1 to 2 hour range, but that's just an estimate. Possible DRI properties as well? Who knows.

 

[Nagelfar]

Lidocaine inspired amphetamine.

This'd be interesting in showing whether a sodium channel blocker that is a DRA (and not a DRI) has any enhanced euphoric (action potential electron resonance playing a factor) faculties; the old idea of that being one of the oft overlooked potential areas of cocaine's efficacy.

Nagelfar, I posted your mph/amphetamine molecule a while a go. I expect it to have DRI properties only; it seems the carbomethoxy binding to a tyrosine residue in DAT gives DRI activity.

but we've been around in circles with the non-ecgonine tropane (para-NO2 according to clubcard) and tropacocaine being capable DRIs having little to do with that. Whether it stabilizes that affinity specifically to a larger or smaller degree, well, I just wonder what beta-phenyl-amphetamine and some of the desoxypipridrols are DR I or As

 

[aced126]

Crap I just realised I commented on ester meth rather than enigma. About enigma, I don't really know the 5HT pharmacophore well and so I couldn't really comment on the effect of the carbomethoxy binding. As you already said, in terms of pharmacokinetics, this will probably be a short acting psychedelic due to ester hydrolysis terminating activity.

 

[Midnight Sun]

Crap I just realised I commented on ester meth rather than enigma. About enigma, I don't really know the 5HT pharmacophore well and so I couldn't really comment on the effect of the carbomethoxy binding. As you already said, in terms of pharmacokinetics, this will probably be a short acting psychedelic due to ester hydrolysis terminating activity.

might be a good way to mitigate DOx/dragonfly duration?

either that or it'd make the residual sides worse, hmm

 

[aced126]

Yeah alright then, the carbomethoxy might not be essential. However compare methylphenidate to its counterpart with a saturated beta carbon (I drew it a while ago, was apparently an already documented releasing agent which caused seizures at low doses). The removal of the carbomethoxy group confers releasing qualities.

 

[aced126]

Yeah good idea Midnight, presuming the molecule pharmacodynamics aren't significantly altered due to the new moiety.