2-bromo-amphetamine

[yoyoman]

I've seen this pop more on some shady websites but I wonder if its going to be 2-FA/FMA's replacement?

Any guess to its action? The fluorine on 2 position seemed to stop some of the euphoria from regular amphetamine. I'm wondering if they are going to try Bromo, Chloro, etc

Its either going to be worse or better.

 

[Solipsis]

Ya I think 2-FA is mostly a dopaminergic drug making it more similar to the rather functional but less fun dexamphetamine, it may be even less recreational than dex which certainly can be nice in larger doses but it's ultimately pretty different from the much more serotonergic 4-FA etc.

2-MA has also been made which again is rather dexamphetamine-like but weak.

We won't know until it is tried, but I would not count on 2-BA being very strong or recreational.

I personally don't expect it to be like 4-halo-amphetamines in most regards so it is doubtful it has the serotonergic toxicity but it is bad territory on principle if you ask me.

 

[Limpet_Chicken]

What is the specific reason that para-halo or presumably other para-electronegative as hell EWGs result in the severe serotonergic neurotoxicity when there is only one (two?) ring substituents, not counting the sidechain in the 1-position of the aromatic ring? and not either when there are multiple substituents on the ring or when a single one only remains then when the EWG is relocated to a different position on the ring?

 

[Solipsis]

Eh, I think 3,4-dichloroamphetamine is still toxic as hell but might be mistaken.

Seems to be correlated with some affinity for the serotonergic terminal, whether it is SERT or VMAT2 or something I do not know. But some of the substitutions you mention abolish affinity for the serotonergic release altogether so it appears that this prohibits the transporter proteins from welcoming the trojan horse before it then somehow gets the neuron so rekt that many wither and die.

4-FA still fits the bill of EWG but apparently there is not really significant damage done. So it's really a quite specific range of compounds with specific pharmacological affinities. 4-MA actually also sounds pretty terrible. I do not know if it wreaks havoc in quite the same way, but I would hardly be surprised because it can really chronically bomb your serotonergic function from the sound of anecdotal intoxications (no bad trip by any measure, but after that, lasting personality changes possible from one exposure etc). Methyl is hardly an EWG lol, but apparently it may still fit the bill.

Correct me if I'm wrong. pCA has long been a little bit of a mystery and at least a topic of much discussion. Especially when 4-FA popped up and now that we also see 4-CMC etc. 4-FA has much longer claimed to not be neurotoxic and more recently 4-CMC and 4-BMC were also said to not follow these mechanisms. I have yet to see the studies backing it up so resort to praying for users that this is right.

[hmm how much does this explain: http://www.nature.com/articles/srep06344 ]

 

[aced126]

Eh, I think 3,4-dichloroamphetamine is still toxic as hell but might be mistaken.

Seems to be correlated with some affinity for the serotonergic terminal, whether it is SERT or VMAT2 or something I do not know. But some of the substitutions you mention abolish affinity for the serotonergic release altogether so it appears that this prohibits the transporter proteins from welcoming the trojan horse before it then somehow gets the neuron so rekt that many wither and die.

4-FA still fits the bill of EWG but apparently there is not really significant damage done. So it's really a quite specific range of compounds with specific pharmacological affinities. 4-MA actually also sounds pretty terrible. I do not know if it wreaks havoc in quite the same way, but I would hardly be surprised because it can really chronically bomb your serotonergic function from the sound of anecdotal intoxications (no bad trip by any measure, but after that, lasting personality changes possible from one exposure etc). Methyl is hardly an EWG lol, but apparently it may still fit the bill.

Correct me if I'm wrong. pCA has long been a little bit of a mystery and at least a topic of much discussion. Especially when 4-FA popped up and now that we also see 4-CMC etc. 4-FA has much longer claimed to not be neurotoxic and more recently 4-CMC and 4-BMC were also said to not follow these mechanisms. I have yet to see the studies backing it up so resort to praying for users that this is right.

[hmm how much does this explain: http://www.nature.com/articles/srep06344 ]

Just to make note: one cannot gauge neurotoxicity on the basis of how the drug makes them feel afterwards. A drug might be neurotoxic but it might be too subtle to notice subjectively, or might only manifest at a much later time. With that said, 4-FA indeed seems to be much less neurotoxic to its other halogenated counterparts.

http://www.sciencedirect.com/science/article/pii/0028390875900994

All the 4-halogenated amphetamines produced a dose dependent reduction in whole brain serotonin and 5HIAA levels, with the chloro analogue producing the greatest reduction. But also of importance is that the Cl and Br analogues maintained or increased this reduction after 1 week, but with the F analogue, levels were back to normal within a day. Also of note is that a SERT reuptake blocker completely attenuated the reduction in levels of 5-hydroxyindole, pointing out to the crucial role SERT plays in neurotoxicity.

 

[Cotcha Yankinov]

I'm curious how much of this is relevant to humans re: MDMA neurotoxicity, considering the typical route of uptake of harmful molecules is at fault with these amphetamines just like MDMA, but yet there is still so much debate about whether human users of MDMA are suffering neurotoxicity (although I think things are leaning towards a yes to neurotoxicity).

I would assume the typical factors like temperature are important. I noticed there seemed to be inhibiton of TPH with one of the compounds (which in my eyes is a big red flag). Was that due to denaturing of TPH or serotonin terminal loss (or both)?

 

[Limpet_Chicken]

LMAO I wasn't implying Me WAS an EWG I was simply making the point that EWGs on the para position without any companion, seem to get all lonely and pissy, taking it out on whatever hunk of meat and wetware surround them. There seems often to be a significant difference between electropositive groups there (alone still don't seem too pleasant on the face of it but for usually different reasons), in fact 4-monosubstitution seems pretty bad news generally speaking. 4-Me-AMP, 4-MMA, MeS- etc.

Para-methyl seems particularly toxic stuff. How do the other para-alkyl substitutions having reasonable chain length fair in comparison, does lengthening the chain from methyl to ethyl, Et to Pr, changing from primary to secondary n-Pr to iPr result in an increase or decrease in toxicity in these?

Also, I was always under the impression that para-iodo was the worst of the halides? is it known how badly/if 4-nitro or 4-cyano substitution results in similar neurotoxins? not that I have the slightest interest in synthesizing either or taking them for that matter. they would be interesting to compare if already known due to the second-messenger selectivity of DOCN and DON/2C-CN/2C-N