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2-FA, 3-FA, 4-FA neurotoxicity

polaroid

polaroid

Bluelighter
Joined
Jan 31, 2010
Messages
53
What do you think about this topic?

In short: OP is saying that halogenated amphetamines have nearly the same structure as chloroamphetamines. And chloroamphetamines are known for selectively kill serotonin neurons.

The ONLY different between the research chemical 4-FA and the highly- neurotoxic Para-chloroamphetamine (4-CA) is the substitution of a single atom -- a fluorine atom for a chlorine atom.
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Originally Posted by Wikipedia
[Para-chloroamphetamine, aka. 4-CA] is used as a neurotoxin by neurobiologists to selectively kill serotonergic neurons for research purposes, in the same way that 6-hydroxydopamine is used to kill dopaminergic neurons.
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http://www.drugs-forum.com/forum/showthread.php?t=175262
 
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The guy has a point. Firstly amphetamine is one hell of a shitty neurotoxic stimulant... And secondly, this is more on chemistry, fluorine is kind of a special one in the group of halogens. It's incorrect to put it aside chlorine and say that it's as similar to chlorine as chlorine is similar to bromine etc., because fluorine has some different properties and can't be used in many situations as a substitute for chlorine, bromine, or iodine. An atom of fluorine is lighter, smaller, electronegativity difference between F and Cl is much bigger than difference between Cl and Br. Just look how HCl (aq), HBr (aq), and HI (aq) are all strong acids and HF (aq) is far from being a strong acid. For instance in organic synthesis often HCl (aq), HBr (aq), and HI (aq) are interchangeable but HF (aq) would be no good substitute. Also, this one concerning 2,5-dimethoxyPEAs and SAR - look up activity thresholds and subjective effects for 2C-B, 2C-C, and 2C-I vs. 2C-F

I don't feel too good so I won't write at length about F vs. other halogen elements. However, by no means I state "this is 100% true what this guy wrote" or "this is 100% wrong what this guy wrote". I'm not really into stimulant amphetamines SAR because this class of drugs don't interest me much.

OP said:
I explained this if you read my post carefully -- I used the examples of chlorpheniramine vs brompheniramine -- two OTC antihistamines with markedly similar pharmacological profiles. In fact, they are a good analogy for 4-FA vs. 4-CA because:

WHY USE CHLOR/BROMPHENIRAMINE AS AN ANALOGY FOR 4-FA/4-CA

1) Chlorpheniramine and Brompheniramine also differ by ONE HALOGEN ATOM.
2) Chlorpheniramine and Brompheniramine also are biologically active in the CNS.
3) Chlorpheniramine and Brompheniramine also contain single highly electronegative substituents on a phenyl ring.
4) Chlorpheniramine and Brompheniramine are extensively studied in the medical literature.

Read more: http://www.drugs-forum.com/forum/showthread.php?t=175262#ixzz1k7bwKpiE
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This is a stupid comparison. He didn't mention fluoropheniramine. Isn't it for a reason?
 
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Expect similar neurotoxicity to dextroamphetamine for 2/3/4-FA. Perhaps a little more for 3-FA due to extensive DA release, and perhaps even a little less due to how hard it is to take the fluorine atom off, not going to metabolize into toxic products. That thread sounds like misinformation that wouldn't fly here on bluelight.

Neuropharmacology (1975), 14(10): 739
The ability of 4-chloroamphetamine, 4-bromoamphetamine, and 4-fluoroamphetamine to deplete brain 5-hydroxyindoles and some pharmacokinetic properties of these drugs were compared in rats. Half-lives of the three compounds in rat brain were 3.7, 4.4, and 5.7 hr, respectively for the 4-fluoro, 4-chloro, and 4-bromo amphetamines. The tendency of the drugs to be associated with particulate material in brain homogenates or to prefer an organic versus an aqueous phase in uitro varied in the order 4-bromo > 4-chloro > 4-fluoro. This order of activity also applied to the inhibition of monoamine oxidase in vitro. All three 4-haloamphetamines reduced the activity of tryptophan hydroxylase and lowered the levels of serotonin and 5-hydroxyindoleacetic acid in whole brain initially. With 4-chloroamphemine and 4-bromoamphetamine, the depletion of brain 5-hydroxyindoles lasted for at least a week. 4-Fluoroamphetamine, in contrast, lowered serotonin and 5-hydroxyindoleactic acid levels only for short times (2-6 hr) after drug injection, and 5-hydroxyindole levels were essentially back to normal within 24 hr. Prior treatment with an uptake inhibitor prevented the serotonin depletion by all of the haloamphetamines, indicating they all required the membrane uptake pump for entry into the neurone. The effect of 4-bromoamphetamine, like that of 4-chloroamphetamine, could be reversed by subsequent injection of the uptake inhibitor after short periods but not after 24-48 hr. The failure of 4-fluoroamphetamine to produce a long-lasting depletion of brain serotonin like that produced by 4-chloroamphetamine or 4-bromoamphetamine may reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines.
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Nichols et al. found 4-fa to lack MDMA-like neurotoxicity, let alone PCA-like neurotoxicity.

ebola
 
polaroid said:
What do you think about this topic?

In short: OP is saying that halogenated amphetamines have nearly the same structure as chloroamphetamines. And chloroamphetamines are known for selectively kill serotonin neurons.
Click to expand...

Saying 'nearly the same structure' in molecular SAR may be a true statement, yet it does not follow that they retain the same method of action. Especially in peripheral effect and metabolism.
 
Any other views on this? I saw the thread on that other forum, and as someone who has enjoyed 4-FA and would like to try 2-FA I was a little worried! There doesn't seem to be any significant research showing neurotoxicity or big dangers from 2, 3 or 4-FA though? Hrmmm.

My warning bells were triggered by that thread when the guy started rambling on about multivitamins and stuff at the end!
 
ebola? said:
Nichols et al. found 4-fa to lack MDMA-like neurotoxicity, let alone PCA-like neurotoxicity.

ebola
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^This
If my understanding is correct, the reason for this is that the para-fluorine blocks para-hydroxylation (by MAO?) which I believe is a necessary step in the formation of oxidative metabolites. However, in the case of pCA, the less electronegative chlorine doesn't compete as well with oxygen, and the molecule is para-hydroxylated, with the chlorine moving over a position on the ring, forming a particularly nasty metabolite for some reason. This also means that 2-FA and 3-FA likely do not lack neurotoxicity in the same way 4-FA does.
Hmmm... if 3-FA is para-hydroxylated, then it would form a metabolite analogous to that of pCA. I wonder if it's similarly nasty.
 
Honestly, it's impossible to say, since we hardly even know how neurotoxicity works in the first place. You put your brain and body on the line whenever you take an untested chemical.
 
I enjoy 2-FA, 3-FA, and especially 2-FMA more than dexamphetamine (my previous all time favorite) and even d-meth when used as an ADHD drug. I just got a vyvanse script, but i'm going to just stash it away while i got 2-FMA. I used to have to take like 12mg xanax throughout the day with d-meth to calm the anxiety (shards, street stuff, so who knows what else is in it, its not desoxyn for sure)

Now I take 1mg klonopin in the morning and i'm anxiety free the whole work day. 2-FMA fully substitutes and is even better than plain amps IMO.

-----
What would it take to find out the metabolites? Someone like me taking 2-FMA everyday and pissing into a cup and have someone analyze it? I'm curious..
 
Here is a copypasta from a different forum

Okay, so 4-FA neurotoxicity is a hot topic nowadays and most of people know very little about it and spread disinformation. I'm not claiming to be a pharmacist, nor a doctor, but these studies back up my claims. Now read:


First thing needed to know is, that effects of halogenated amphetamines are different in rat brains compared to human, so we can't apply every research on rats to humans. http://www.ncbi.nlm.nih.gov/pubmed/17038507

Second thing I want to address is 4-FA comparison to chlorinated amphetamine, such as 4-CA. 4-CA is not neurotoxic in humans! 4-CA has been used as an antidepressant in the seventies.

Considerable clinical application of 4-CA has been made, and it has been found effective as an antidepressant when used chronically at levels of 75 mg/day (van Praag et al., 1971; van Praag and Korf, 1976). There are very few side effects noted and the drug is tolerated very well. However, indications of raphe-nucleus degeneration (Yunger et al., 1974) and related neurotoxicity (Harvey and McMaster, 1976) in experimental animals have discouraged further clinical study.
The same applies to 4-CMA

The N-methyl homolog of 4-chlorophenylisopropylamine (80, para-chloromethamphetamine p-CMA, Ro 4-6861, S-33) was also found to be a potent and long-lasting depleter of brain serotonin (Fuller et al., 1965). It has been compared with methamphetamine in normal subjects (Verster and van Praag, 1970) and has been evaluated clinically in comparison with 4-CA (79) as an antidepressant (Deniker et al., 1971; van Praag et al., 1971; van Praag and Korf, 1976). Typical dosages were between 60 and 90 mg/day, administered chronically for several weeks. There appeared to be no physical or psychic dependence developed, no cardiovascular complications, and no sleep or appetite problems.

Third thing is, para-halogenated amphetamines deplete serotonin, but in a reversible way in humans, compared to irreversible in rats.
This finding indicated that p-fluoroamphetamine might share with p-chloroamphetamine the action that is responsible for short-term 5-HT depletion but lack the property of p-chloroamphetamine required for long-term effects. A later study confirmed that p-fluoroamphetamine was less potent than p-chloroamphetamine in depleting brain 5-HT (Harvey et al., 1977; Fuller, 1978).
With 4-chloroamphetamine and 4-bromoamphetamine, the depletion of brain 5-hydroxyindoles lasted for at least a week. 4-Fluoroamphetamine, in contrast, lowered serotonin and 5-hydroxyindoleacetic acid levels only for short times (2–6 hr) after drug injection, and 5-hydroxyindole levels were essentially back to normal within 24 hr.
The failure of 4-fluoroamphetamine to produce a long-lasting depletion of brain serotonin like that produced by 4-chloroamphetamine or 4-bromoamphetamine may reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines.
You see? 4-FA doesn't deplete serotonin in rat brain in irreversible way.

Speculation alert: Looking at the atom radius, there's a chance that 4-FA is less neurotoxic than regular amphetamine, since data shows that serotonine depletion goes in hand with atom radius in para (4) position. http://www.ncbi.nlm.nih.gov/pubmed/15677348

Further reading:
http://www.erowid.org/archive/rhodiu...a.sar.hop.html
http://www.sciencedirect.com/science...28390875900994
http://www.ncbi.nlm.nih.gov/pubmed/14654099
http://bitnest.ca/Silo42/10.1111/j.1....tb31518.x.pdf (FULL TEXT)


TL;DR
1. 4-CA is not neurotoxic in humans, it's been proven to be safe in doses 75-90mg/day for a year. Same applies to methylated version.
2. Serotonin levels get back to normal in 24 hours after 4-FA indigestion, compared to ONE WEEK after 4-CA indigestion (and bigger halogenated amphetamines)
3. Therefor 4-FA is nothing like other halogenated amphetamines.
4. 4-FA has lesser addictive potential than plain old amphetamine, due to longer half-life
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^ This is probably the dumbest thing I have ever read.

1. Yeah, pCA and pCMA were *tested* as antidepressants, but I read that study and they were only talking about efficacy when the drug was actually administered. I didn't see anything about followups. They have not, by a long shot, been "proven" safe in humans. The only reason those studies were ever even conducted was that they thought the depletion of serotonin was only a consequence of serotonin release and thus antidepressant efficacy, not neurotoxic damage.
2. Yes, 4-FA apparently does not cause neurotoxic damage in mice (judged by 5-HT content compared with the profile for serotonergic neurotoxins), and so probably not in humans.

"Speculation alert: Looking at the atom radius, there's a chance that 4-FA is less neurotoxic than regular amphetamine, since data shows that serotonine depletion goes in hand with atom radius in para (4) position."
Except the covalent radius of fluorine is twice that of hydrogen.
 
^^ Stop trolling dude, they're all non-toxic cause SWIM says so :p

Honestly, we really have no clue about FA toxicity in humans, and probably won't for a very long time, I suggest keeping doses around that of d-amp/d-meth
 
Yeah well having explored well into the 300+ mg range on 4-FA I can safely say that there's no reason to go there anyway. Hahah.
 
thanks (I now lack access to full texts of journal articles).
 
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