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RCs 4-bromomethcathinone (Brephedrone)

Bromine substitution at the ring 3- or 4-position of methcathinone enhances potency at serotonin uptake transporters.

Nicholas V. Cozzi and Kevin F. Foley


Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27834

Abstract

We previously reported that methcathinone, the aryl ketone analog of methamphetamine, was an inhibitor of monoamine uptake into human platelets and cultured cells (Cozzi et al., Soc. Neurosci. Abs., 24, 341.8, 1998). Based upon our pharmacophore model for the amphetamine binding site in the plasma membrane serotonin (5-HT) uptake transporter, it was hypothesized that halogen substituents on the phenyl ring of methcathinone would have a favorable effect on binding affinity at the 5-HT transporter. To test this proposal, 3-bromomethcathinone and 4-bromomethcathinone were synthesized and evaluated for their abilities to inhibit [3H]5-HT uptake into human platelets in vitro. In support of our hypothesis, both of the bromine-substituted compounds were about 15-fold more potent than methcathinone as 5-HT uptake inhibitors: 3-bromomethcathinone inhibited [3H]5-HT uptake with an IC50 of 2.05 ± 0.17mM while 4-bromomethcathinone had an IC50 of 1.83 ± 0.5 mM These results lend support to our model of the substrate binding site in the 5-HT uptake transporter. The model predicts that there is a pocket within the substrate binding domain of the transporter that can accommodate substituents at the ring meta-or para-positions of arylalkylamine ligands. Occupation of this pocket by such substituents leads to increased stability of the ligand-protein complex.
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Doesn't say much about the potential for neurotoxicity there.

Just that it has stronger serotonergic activity as a reuptake inhibitor, and I would be pretty surprised if it wasn't a strong 5HT releaser also. Very surprised in fact.

Buggered if I would try it though..no chance.
 
I doubt its likely to kill. 'Just' produce profound and long lasting cognitive, memory and sleep deficits.
 
Actually, the question is more: are YOU retarded? Is a short lasting shitty high worth the potential for serious, long lasting brain damage? Yes, the cathinones have different pharmacology. The risk with halo amphetamine derivatives is simply too high to make it worthwhile. When we say this is neurotoxic, we aren't talking MDMA-neurotoxic. We're talking about a derivative if a drug that is used in research to selectively destroy serotonergic neurons. Frankly, if that isn't enough to dissuade you, then there is no hope. Fry away your brain if you must but don't encourage other people to do so as well.

It may well be that this stuff is actually non neurotoxic however I imagine an appreciable fraction of it is deoxygenated at the benzylic carbon to yield the parent non-cathinone amphetamine as a matter of course in it's metabolism. Then it WILL be neurotoxic.
 
I don't like the idea of having a bunch of 4-bromoephedrine (a 1' metabolite...) floating around in my blood. Eugh.
 
^neither do i, thanks for that speculation/info matt. i wouldnt have touched the chem anyways but shit son.

is there possibility of bromine impurity?
 
I think the term: "neurotoxic" needs to be better defined in this conversation...
I'm sure all or most people know that a "Neurotoxic" substance is something that causes: temporary damage, permanent damage, or total (neural / brain) cell death. BUT, there is actually a 4th outcome, that the "Neurotoxic" drug does NOT cause any neural cell damage at all!
Just b/c a drug is neurotoxic does not mean it will actually be neurotoxic when ingested, it just means that the drug has the POTENTIAL to cause cellular damage. The amount of drug taken, the ROA used, the unique physiology of each person, and I'm sure many other factors, all determine whether or not a "neurotoxic" drug will actually be neurotoxic, and just how neurotoxic it will be.


I am NOT suggesting this drug, or any of the RC's / analogues, etc... are safe, infact I'd bet that this 4-Bromo substance is probably very dangerous. All I'm saying is that a distinction needs to be made between a substance having the potential for being neurotoxic, and a substance known to be neurotoxic when taken at xxmg's via yy ROA....
 
MattPsy said:
Actually, the question is more: are YOU retarded? Is a short lasting shitty high worth the potential for serious, long lasting brain damage? Yes, the cathinones have different pharmacology. The risk with halo amphetamine derivatives is simply too high to make it worthwhile. When we say this is neurotoxic, we aren't talking MDMA-neurotoxic. We're talking about a derivative if a drug that is used in research to selectively destroy serotonergic neurons. Frankly, if that isn't enough to dissuade you, then there is no hope. Fry away your brain if you must but don't encourage other people to do so as well.

It may well be that this stuff is actually non neurotoxic however I imagine an appreciable fraction of it is deoxygenated at the benzylic carbon to yield the parent non-cathinone amphetamine as a matter of course in it's metabolism. Then it WILL be neurotoxic.
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Did you read the link I posted? Since having a beta ketone annihilates potential affinity for the VMAT2, which is required for monoamine release, which is required for PBA\PCA's neurotoxicity to manifest...it's almost impossible for what you're saying to be true in this light!

And anyone who's tried both bk-MDMA and MDMA [or 4-FMC and 4-FMA] will be able to tell you, no appreciable amount of metabolites are formed from deoxygenation at the beta carbon...you realize it undergoes demethylation first into the beta-hydroxy?
 
Incredible, I can't believe they are selling this. I don't care about the argument that the neurotoxicity is merely conjecture at this point, look at the risks mentioned in this thread and in other places - now how the hell can a high be worth that kind of damage? Even the news depresses me.
While at another forum it is described as coming quite close to ecstasy and little if anything is mentioned about neurotoxicity. What are they thinking, is there not one person there who has heard of the dangers of haloamphetamines? Indeed, mephedrone is pushing it - even unacceptable IMO. Flephedrone felt wonderful to me but I strongly reconsidered my entire methcathinone use at some point and have now for a while rejected taking any. (Of course I am abstaining from almost anything now but ok).

Even if it's better than ecstasy, fuck it, I'm NOT going for broke. I have bk-PMMA but it is for collection purposes only and I have never felt like it was okay to take the plunge with that. And similarly there are so many others right now that should be avoided. I also recommend people avoid MDPV and MPA and a shitload of others.

I say you, don't be tempted by stories about putative absence of neurotoxicity in vitro or animal models - it's not like that is the only thing to worry about anyway. Even if none of your neurons are directly harmed, it's not like it is fun to be drained of monoamines and have your recycling and synthesis pathway enzymes undermined.

Ive sent an urgent message to a webmaster of a remaining source. I wanna remind you that details are source discussion but I also recommend that as many as possible send messages as well to persuade them so that maybe we can save the health or lives of some people. A moment of truth for HR, right?
 
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Great, the second vendor (and only other one I know) has agreed to remove the product from their catalog shortly. :)

I have debated the subject and reasons for great likelihood of danger elsewhere and can copy it here, I will do that now:

(By the way, if you read the second quote and the article except from Nichols you will see that bromo is quite possibly the worst one. If beta-ketonating it increases dopaminergic activity that could make it slightly less toxic but considering the side-effects reported by some people who have used brephedrone it seems serotonergic activity is still significant and it would be safer to assume that with the activity the effects on the metabolic enzymes is also carried over and thus you should NEVER TRY IT.)

Did you know though, that it is a phenomenon that after incidents start to happen with certain compounds, popularity can surge rather than collapse?

If vendors read that an increasing number of other vendors stop making the product available they will see that its not the way to go to have it synthesized and may opt for an alternative. In general I agree that repression is not the answer when it comes to drugs. But when RCs are only in their early stages, making a big fuss about it could give it a bad name with both potential users AND (potential) vendors.

I admit there is no evidence that the compound is actually that harmful but if you consider the square relations between the following compounds:

4-FMP (4-FA) → 4-FMC
↓............................↓
4-BMP (4-BA) → 4-BMC

you can see that 4-FA (parafluoroamphetamine) is generally OK, 4-FMC (flephedrone) is already dubious and suspected to be worse than mephedrone (but possibly less bad although I think never that much), 4-BA (parabromoamphetamine) and other haloamphetamines EXCEPT fluoro is toxic so by induction you would expect 4-BMC (brephedrone) to be as harmful or even more with added meph cardiovascular issues from the beta-hydroxy metabolites.

Like I said: subjective reviews are worthless to me. 4-MA is also to be avoided like the plague because I hear that it can cause long lasting measurable detrimental changes to the brain, while I don't think that it is that noticeable from the effects. The effects may initially indeed be pleasurable, but I suspect when use is continued side-effects will surface more and more and the more you have used the more permanent brain damage you will have caused. Something similar is what I fear with brephedrone and only a fucking idiot would take that chance looking at the relational square I provided.

[...]

If you know a thing or two about drug trend politics and dynamics and can argue the futility of trying to act on this threat I am open to your wisdom, but let's debate about this at the very least, but preferably do what we can so that we can be proud to call ourselves an HR forum.
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Some more good info on the haloamphetamines that you might extrapolate:

Hyperthesis said:
This could be the answer:

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.​


I think that ALL amphetamines are neurotoxic to some degree, depending on dosage and frequency of usage, of course. But the 4-F-derivative stands far behind 4-Cl/4-Br/4-I/4-Me with respect to brain damaging effects. Its's all relative, isn't it. Or in Paracelcus' famous words: „Dosis sola facit venenum“ :)
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Herbal~Jah said:
seriously....these RC's are getting to be ridiculous. Why can't you people just use the drugs that have been around for awhile and studied a lot... lol basically all the ILLEGAL drugs seem to be the SAFE ones... (well most of them)
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The place in the world where they make money on RC's are europe/uk/canada/us, alot of countries(like mine) make things illegal very fast. To combat this there are semi-big chemical-laboratorys who just develop more synthetic cannabinoids, stimulants so they have a few options when jwh-018 gets banned they have 3-4 new ones waiting.

What they are going for are effect, not really worried regarding side-effects. Some vendors care about the healthrisks and won't sell anything to bad. That is the market today and thank GOD for sites like bluelight so you can do some research.
 
Yeah I thought mephedrone was bad already, this is just ridiculous.
 
Great, the second vendor (and only other one I know) has agreed to remove the product from their catalog shortly.
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You may have saved lives :)

What were they thinking putting this out there in the first place?? Jesus some people have no conscience.
 
So from what I've gathered the halogenated amphetamines cause serious irreversible damage to 5-HT receptors, but 4-FA doesnt?

Why would this be?

Just curious.
 
Solipsis said:
Incredible, I can't believe they are selling this. I don't care about the argument that the neurotoxicity is merely conjecture at this point, look at the risks mentioned in this thread and in other places - now how the hell can a high be worth that kind of damage? Even the news depresses me.
While at another forum it is described as coming quite close to ecstasy and little if anything is mentioned about neurotoxicity. What are they thinking, is there not one person there who has heard of the dangers of haloamphetamines? Indeed, mephedrone is pushing it - even unacceptable IMO. Flephedrone felt wonderful to me but I strongly reconsidered my entire methcathinone use at some point and have now for a while rejected taking any. (Of course I am abstaining from almost anything now but ok).

Even if it's better than ecstasy, fuck it, I'm NOT going for broke. I have bk-PMMA but it is for collection purposes only and I have never felt like it was okay to take the plunge with that. And similarly there are so many others right now that should be avoided. I also recommend people avoid MDPV and MPA and a shitload of others.

I say you, don't be tempted by stories about putative absence of neurotoxicity in vitro or animal models - it's not like that is the only thing to worry about anyway. Even if none of your neurons are directly harmed, it's not like it is fun to be drained of monoamines and have your recycling and synthesis pathway enzymes undermined.

Ive sent an urgent message to a webmaster of a remaining source. I wanna remind you that details are source discussion but I also recommend that as many as possible send messages as well to persuade them so that maybe we can save the health or lives of some people. A moment of truth for HR, right?
Click to expand...


hey Solipsis
you quote mdpv here, is it because you think it´s toxic or because it makles you paranoid ?

peace
 
Cone said:
So from what I've gathered the halogenated amphetamines cause serious irreversible damage to 5-HT receptors, but 4-FA doesnt?

Why would this be?

Just curious.
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yes i too am curious about why the uproar about 4-bmc, and not 4fa?

also, i do believe the beta-ketones have less potential for neurotoxicity (i.e. bk-mdma vs. mdma), but that may not make it safer than mdma. I've tried 4bmc, and it seemed mild (200mg dose)... even more so than bk-mdma. I've also heard that in some countries 4bmc is quite popular. wouldn't we have heard of multiple cases of serotonin syndrome? I know neurotoxic drugs can cause damage much later after use, but i'd think there'd be some report of issues.
NOTE: I do not want anyone to misconstrue my questions as implying this substance is safe, these are merely questions i feel are worth asking.
 
Dose is 250mg oral if you've got clean brephedrone.

If it doesn't fully dissolve, it's obviously not pure.
 
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