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Stimulants of the Future II

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But I was wrong, too: Even when the pyrrolidine aromatizes to pyrrol, the ring won't be charged. So, the concerns about a MPTP-like derivative were not justified. Silly me
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*slaps forehead*

Of course! It's so simple. In a pyrrole ring, just like in an indole ring, the nitrogen has one bond free for the methyl, so it won't become charged, unlike a pyridine ring, where the nitrogen already has a double bond and a single bond.

Now we are all gonna feel real silly.
 
Hehe, so much paranoia for nothing.
So Prodilidine would be a good go then?

And how likely is that oxetane to be broken down in vivo compared to phenmetrazine?
It should (I guess) cross the BBB better that cathinone.
Oh, found theese:
ncontent

http://www3.interscience.wiley.com/journal/119054299/abstract
ncontent

http://www3.interscience.wiley.com/journal/113385629/abstract

How would this molecule compare to cathinone and phenmetrazine in activity?
 
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MurphyClox said:
Looking at the structure that Wiki provides - it isn't! There's clearly a methyl an the pyrrols's nitrogen.

But I was wrong, too: Even when the pyrrolidine aromatizes to pyrrol, the ring won't be charged. So, the concerns about a MPTP-like derivative were not justified. Silly me :|

- Murphy
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I'm not talking about the structure of prodilidine proper, no one is. We're talking about what happens to it in vivo. And what happens to it, primarily, is N-demethylation. Definitely doesn't become charged.
 
MurphyClox said:
Naahhhhh FnB! Ethylene oxide ("oxirane") is a 3membered ring, which is indeed very toxic. The depicted molecule contains a oxetane - or oxacyclobutane. For in vivo-related issues, it's stable enough and toxicity is far lower.

- Murphy
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I would have thought a 4 membered ring was strained enough to undergo opening under fairly mild conditions. A 5 membered ring is strained but fairly stable (105' bond angle as oppose to 109' for a cyclohexyl ring) but 90' & a heterocycle like oxygen with two lone pairs making the ring strain worse.

I know there are drugs with a 3 membered ring in their structure that don't ring open (eg tranylcypromine), but that's because it's an all carbon ring (alicyclic).


PS MPTP is a by product of the fucked synthesis of MPPP. The batch in N California came about because the person synthing it sunbstituted ice/salt water for dry ice (was essential to keep reaction below -20'C) ending up with tertiary alcohol dehydration/elimiantion of water (to MPTP) rather than esterification (to MPPP)
 
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Ok, on topic, I have an idea: 3,4-methylenedioxy-amfechloral! (or N-(2,2,2-trichloroethylidene)-MDA)

Legal except for analogue acts, and metabolizes to MDA and chloral hydrate! =D

mdamfechlor.png
 
/navarone/ said:
^^ Haha! Your using Paint! Loooser! :D
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Didn't use paint, I used photoshop (well, actually a freeware equivalent)... want me to put some fancy bevels & drop shadows in it as proof? :D

I was just lazy, couldn't be bothered to open chemsketch just to draw something like this...
 
Another idea wrt. prodrugs: MD-fenethylline!

Fenethylline is a prodrug which metabolizes to amphetamine and theophylline... so if you add the nifty MD group you'll get a drug that metabolizes to MDA and theophylline!

You could press it into pills with a tea cup logo =D
 
ebola? said:
Given how poorly redoses work with empathogens/entactogens, what should we expect of the efficacy from these prodrugs?

ebola
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Who knows? The one with the chloral hydrate metabolite (MD-amfechloral) would probably be a blast... GABA-activity along with entactogen activity, hmm..

The MD-fenethylline has the advantage that you could add a methyl group to get a drug that metabolizes to MDMA, but would probably be inefficient: according to wiki, an oral dose of 100mg of fenethylline will only result with about 25mg of amphetamine in your system. Makes you wonder what happens to the rest of it... Also makes you wonder if an ester link (instead of the ethane bridge) between the amines would be more efficient?

Some crazy chemist should make these compounds and bioassay them... else we will never know...
 
an oral dose of 100mg of fenethylline will only result with about 25mg of amphetamine in your system. Makes you wonder what happens to the rest of it...
Click to expand...

The rest is released as a xanthine (bet the amphetamine portion only accounts for 25 percent of RMM of drug)


Fenethylline is a prodrug which metabolizes to amphetamine and theophylline... so if you add the nifty MD group you'll get a drug that metabolizes to MDA and theophylline!
Click to expand...


Don't count chickens... the primary site of attack could be the methyledioxy ring so you'd end uo with alphamethyldopamine & theophyllline
 
Don't count chickens... the primary site of attack could be the methyledioxy ring so you'd end uo with alphamethyldopamine & theophyllline
Click to expand...

Well, then what about replacing the ethyl bridge between the amines with a dicarboxyl ester, that would break faster?

Just think of the possibilities... As you'd have theophylline-MDMA which you could call "Tea X" you could also have theobromine-MDMA which you could call "Chocolate X"! :D
 
Anyway MANY of theese 'linked' compounds have been made:
Look what i found:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=108517&loc=ec_rcs

Anyway back on topic. I was wondering about 2 things:

1) I always thought IAP was a neat MDMA analogue because of its non-neurotoxic properties. Though it lacks of polarity on the dioxy regions of MDMA which make a difference. So what would be an inteligent way to solve this?
Attaching 2 halogens atoms on those regions? 2 Keto groups (indanedione, hmm an anticoagulant and rodenticide, maybe not so smart)? Or 2 double bonds going from 3->2->1?
(Oh this one is also interesting, 5-IT. Mentioned bu Shulgin, it is active at 20 mg and lasts 12 hours.)

2) I pondered about this while looking at bromazepam, would it be a very bad idea to switch the phenyl ring with a pyridazine ring with the nitrogens at the 3,4 positions to increase polarity on those regions. My concerns are not about activity but rather about stability and neurotoxicity...
 
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I always thought IAP was a neat MDMA analogue because of its non-neurotoxic properties. Though it lacks of polarity on the dioxy regions of MDMA which make a difference. So what would be an inteligent way to solve this?
Attaching 2 halogens atoms on those regions? 2 Keto groups (indanedione, hmm an anticoagulant and rodenticide, maybe not so smart)? Or 2 double bonds going from 3->2->1?
Click to expand...

As IAP is only lacking in dopaminergic activity, why not just add another drug to make up the shortfall (eg amphetamine) rather than creating dodgier compounds (indanedione which you said was a rodenticide. Halogens on the trimethylene ring will act like haloalkanes ie will substiutute for hydrogen at NH2 groups, making it potentially a DNA alkylator/nasty chemical) which will be even further down the route of unknown toxicity

PS Amp & IAP was very like MDA from the times I tried the combo
 
Does the drug remain non-neurotoxic if it's administered with a DA releaser?

I thought the reason MDAI was non- neurotoxic was because as a 5HT releaser, it was devoid of DA releasing properties, but when the two were combined, you got the neurotoxicity.
 
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