4-FAR? Flourophenmethrazine??

[Tryptamite]

4-Far is a cool name, lol.Would this function in much the same way as 4-flouroamphethamine function? Or does it make the drug more lipophilic and therefore more potent??

I have yet to see this come up as a research chemical? 4-ethylaminorex was shown an interest in by one seller but the project apparently faded away into nothing? Does aminorex have similar SAR qualities to amphetamine?

What about a 4 subtituted phenmethrazine?

 

[aced126]

It is interesting to compare this to 4-FA, and whether the compound would produce entactogenic effects. We know from this article (http://pubs.acs.org/doi/abs/10.1021/cn4001236) that bulky alkyl groups on the alpha carbon destroy affinity for monoamine release, probably because the compound now isn't a good enough substrate at the monoaminergic transporter to be transported into the neuron. The article also tested the following compound known as MDPPP (1-(3,4-methylenedioxyphenyl)-2-(pyrrolidinyl)-propan-1-one)

The said compound did not produce a DAT-mediated inward current that is typical of dopamine releasers like amphetamine, but instead it produced a DAT-mediated outward current, typical of DAT reuptake inhibitors. In fact the outward current produced was greater than MDPV itself, a known strong DAT reuptake inhibitor. Likewise, this compound turned out to be a reuptake inhibitor as well, with similar potency to MDPPP:

Thus even small steric bulk on the nitrogen also probably lowers the substrate affinity of the compound for DAT, and prevents the drug from entering the neuron and causing release. With that said, I would expect phenmetrazine and analogues to also not be able to release monoamines.

We know that serotonergic releasers normally have entactogenic effects, and this is diminished if the compound simply acts as a serotonin reuptake inhibitor. So 4-fluorophenmetrazine would probably have similar effects to 3-fluorophenmetrazine and be a dopamine reuptake inhibitor.

 

[Tryptamite]

Sorry I made an error. I forgot there was already a 4-methylphenmetrazine on the market and it wasn't highly rated. 3-fluorophenmetrazine is supposedly very enjoyable in higher doses IV'd (we all remember "pro sexull rush" used to describe phenmetrazine.

But the only 4-MAR/Aminorex typre drug we have seen is 4,4-Dimethylaminorex, and that was responsible for a number of deaths. We know from phendimetrazine that substitutions on the Nitrogen lower the potency or have to be demthylated in vitro making it a prodrug.

So for me discussion of aminorex substitutions and possible effects would be ineresting. why are there none on the rc market. i would have thought that after cathinones and substituted amphetamines, phenmetrazine and then 4MAR would be a logical choice. We have seen phenmetrazine played around with a bit but so far no mention of aminorex rcs. are the precursors that hard to get? without going into synth talk I realise cyanide compounds are invloved but this shouldnt be too difficut for big pharmaceutical factories to handle. im sure there are other routes as well.

2-FAR would be a cool name and a cool molecule if it turned out to be a winner.

 

[aced126]

Sorry I made an error. I forgot there was already a 4-methylphenmetrazine on the market and it wasn't highly rated. 3-fluorophenmetrazine is supposedly very enjoyable in higher doses IV'd (we all remember "pro sexull rush" used to describe phenmetrazine.

But the only 4-MAR/Aminorex typre drug we have seen is 4,4-Dimethylaminorex, and that was responsible for a number of deaths. We know from phendimetrazine that substitutions on the Nitrogen lower the potency or have to be demthylated in vitro making it a prodrug.

So for me discussion of aminorex substitutions and possible effects would be ineresting. why are there none on the rc market. i would have thought that after cathinones and substituted amphetamines, phenmetrazine and then 4MAR would be a logical choice. We have seen phenmetrazine played around with a bit but so far no mention of aminorex rcs. are the precursors that hard to get? without going into synth talk I realise cyanide compounds are invloved but this shouldnt be too difficut for big pharmaceutical factories to handle. im sure there are other routes as well.

2-FAR would be a cool name and a cool molecule if it turned out to be a winner.

For substituted aminorex, the synthesis would be doable but it would need precursors much harder to obtain than simply to synthesize aminorex, and it would need some more steps than most RC syntheses I reckon. I think this could be a reason.

I would be careful with aminorex analogues as a lot of them could be potent 5HT-2b agonists which cause cardiac valvulopathy.

 

[Tryptamite]

Megatherium from the hive found this data back in the day:

Aminorex patents

Patent BE628803
Patent US3161650
Patent US3278382
Patent DE2101424

According to ../rhodium/pdf /poos.aminorex-1.pdf the p-halogen analogs of aminorex are more powerfull than plain aminorex:
* aminorex: ED50 = 5.8 mg / kg
* p-bromo aminorex: ED50 = 4.6 mg / kg
* p-chloro aminorex: ED50 = 2.5 mg / kg
* p-fluoro aminorex: ED50 = 1.2 mg / kg

Links don't work.

Stronger doesn't necessarily mean better. I presume it should follow that 4-fluoro-4-methyl-aminorex would be stronger than non-halogenated 4-methyl-aminorex?

Also I realise amphetamine SAR does not account for aminorex compounds but i would just be comfortable trying out the flouro compounds, chloro-amphetamime is very nuerotoxic, and i cant imagine bromo-amp is very good for the brain cells either..

 

[Tryptamite]

Future 4-MAR halogen analogs of abuse

So, making a 4-MAR halogen analog would be -pharmacologically speaking - a shot in the dark.

I got inspired by this:
"Contrary to previously cited work this suggests that aminorex may in fact be as potent an adrenomimetic as amphetamine. In any case, Poos (personal communication) highlighted eight compounds which may have adrenomimetic activity similar to those of amphetamine and methamphetamine.

Shown below and listed in decreasing order of anoretic activity they are:

1) 2-amino-5-(4-fluorophenyl)-2-oxazoline
2) 2-amino-5-(4-Chlorophenyl)-2-oxazoline
3) 2-amino-5-(3-trifluoromethylphenyl)-2-oxazoline
4) 2-amino-5-(4-bromophenyl)-2-oxazoline
5) 2-amino-5-phenyl)-2-oxazoline [aminorex]
6) 2-amino-5-(4-trifluoromethylphenyl)-2-oxazoline
7) 2-dimethylamino-4-methyl)-5-phenyl-2-oxazoline
8 ) 2-amino-4-methyl-5-phenyl-2-oxazoline [4-methylaminorex].

2-amino-4-methyl-5-(4-trifluoromethylphenyl)-2-oxazoline [para-TFM-4-methylaminorex].



Although not mentioned in this work, one would immediately assume that the 4-fluoro- and 4-chloro-phenyl derivatives of compounds 7 and 8 would also have significant anoretic activity. Given the astoundingly simple synthetic process required to produce these compounds, and the fact that the 4-halogen substituted aryl derivatives would require precursors unlikely to titillate the interest of law enforcement agencies, these compounds will most probably be made in future clandestine syntheses. It is also conceivable that some enterprising clandestine chemist will wonder if appropriately substituted methoxy derivatives will have psychotomimetic properties. "

From: ../rhodium/chemistry /future_drugs.html

Poster: Megatherium, methods and discourse, the hive.

Would the compounds highlighted in bold share the same cardiotoxic issues as fenfluramine? N-Ethyl-3-(trifluoromethyl)amphetamine

 

[roi]

4-fluorophenmetrazine and 4-methylphenmetrazine have both been around and suck. I guess 3,4-methylenedioxyphenmetrazine wouldn't be that great either.

 

[Tryptamite]

Yeah I know, I was getting the two classes confuddled in my old age. Oh well, Ill just take some more 4-CHLOROAMPHETAMINE to fix it. Joke! I would not touch 4CA with a shitty stick taped to another stick taped to my penis for good measure lol. And for harm reduction I reccomend staying away from all halogenated amphetamnes/cathinones, etc. aside from those with a flourine on the benzene ring,and while you're at it, duct taping your penis to various objects is a good way to poke yourself in the eye should an atrractive boy/gir/donkey/car walk or drive by (you should be doing cock push-ups).


Seriously though I expect little more input on the subject of substituted aminorex drugs. I have had a good read about and found a few things but I wont post them here as they are only old forum posts themselves. It seems to be a somewhat of a dead end without actual bioassays of the compounds we are talking about to back up our SAR predictions. Even lab tests on some mice.
I am particularly interested in what happens if you move the methyl/flourine/whatever (methoxy perhaps? ) moiety around to other positions on the ring, obiously the N is out of the question unless we are talkng methyl but phendimetrazine is a bit shit apparently. And we already have 4 phenyl substitutions such as (4-phenylchloro)aminorex, and the seemingly dodgy para,4-methylaminorex, but what about a 2 fluoro on the phenyl ring of aminorex or 4-methylaminorex?

 

[aced126]

You can't compare the phenmetrazine class to the aminorex class, especially with movement of the halogen around the ring, because phenmetrazine blocks DAT but aminorex releases dopamine (and serotonin).

 

[sekio]

phenmetrazine is a DA releaser though?

 

[aced126]

phenmetrazine is a DA releaser though?

I don't think it is. On wikipedia it says it is, but the source it gives is a patent (https://www.google.com/patents/US20130203752) which in fact mentions that the compound(s) may be reuptake inhibitors or releasers. I do acknowledge that it mentions phenmetrazine as a specific DA releaser, but I still have uncertainty due to the following:

-If it was a releaser of DA, then incorporating a 4-fluoro might increase SERT substrate affinity greatly and we would see some 5HT release. This doesn't happen at all though, neither does it happen with any substitution on the rings.

-In the study I posted, as well as the specific examples I took, we can see that any added steric bulk on the nitrogen past one methyl group causes the drug to loose DAT substrate affinity.

 

[palmanita]

But the only 4-MAR/Aminorex typre drug we have seen is 4,4-Dimethylaminorex, and that was responsible for a number of deaths.

It was one of the best drugs I've tried though. Strong antidepressant, anxiolytic, mild stimulant and entactogenic effects, lasting all day long and in the doses I've used there was surprisingly little comedown, also sleep was easy afterwards (gladly I was cautious and cut the 80mg(?) sample pill in a few pieces and found 20mg to be strong already, 40mg were an overwhelming flood of euphoria). In my opinion it was just plain irresponsibility to hand out so high dosed samples of a drug with two hours onset and 12+h half life.

A comparable drug would be nice when used responsibly.

 

[adder]

-If it was a releaser of DA, then incorporating a 4-fluoro might increase SERT substrate affinity greatly and we would see some 5HT release. This doesn't happen at all though, neither does it happen with any substitution on the rings.

This is some weird reasoning in my opinion. Even if there is some correlation between dopamine and serotonin release in p-substituted amphetamines, it doesn't automatically mean that any analogue with modified side-chain that is still a DA releaser will be a 5-HT releaser, right?

 

[aced126]

This is some weird reasoning in my opinion. Even if there is some correlation between dopamine and serotonin release in p-substituted amphetamines, it doesn't automatically mean that any analogue with modified side-chain that is still a DA releaser will be a 5-HT releaser, right?

It doesn't but is often the case.

Methcathinone > mephedrone, clephedrone, brephedrone. All have empathogenic effects. Amphetamine > 4-FA, 4-Me-amphetamine, both strong 5HT releasers. What is happening is the ring substitution is lowering DAT substrate affinity and at the same time increasing SERT substrate affinity (this is why all the substituted compounds have dosages often 10 times as much as the unsubstituted amphetamine/cathinone).

If we try the same thing with known reuptake inhibitors such as ritalin: 4-F-eph, 4-Me-eph, 4-F-mph, 4-Me-mph, 3,4-Cl-mph. All have absolutely no affinity as a SERT substrate (even though they might have affinity to simply block SERT, this however doesn't result in empathogenic effects but instead downstream antidepressant effects). Some more examples: adding a 3,4-methylenedioxy substitution to pyrovalerone doesn't confer it 5HT releasing abilities at all.

I think if something is a DAT substrate (the same way dopamine itself functions as a substrate, not some alternate binding site for example), then it has potential to be a SERT substrate with the right substitutions.

Obviously this doesn't imply that "incorporating a 4-fluoro might increase SERT substrate affinity greatly [of phenmetrazine]" but it is pretty suggestive, in my opinion at least.