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The difference between Methcathinone and 4Methylmethcathinone?

Furious George

Furious George

Ex-Bluelighter
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Mar 28, 2008
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Hi Guys,

I'm having a debate with someone on another forum about why they consider methcathinone to be "insanely neurotoxic" whilst they reject outright that 4MMCat is neurotoxic. There line of argument is:

"Any changes to molecular structure completely alter the pharmacological action of a drug.
Adding a 4 in the methyl position "seem" to vastly decrease dopamine displacement and increase 5HT affinities.
I have abused mephedrone and mcat (well, not mcat, but a pro-drug) and it is very obvious to see the difference between the two.
The main neurotoxicity of MA and MCAT come from oxidative damage and DA receptor damage (they also have a whole host of other nasty mechanisms), this is not evident at all with mephedrone."

So is this an accurate explaination or not. I'm no chemist, it's all Greek to me.
 
Mods? You guy are chemistry wizards, *starts kissing arse* with brains as big as yours I bet you could easily answer my question.:D
 
I've never heard of MCAT being "insanely neurotoxic." In fact, the only neurotoxicity that I've read about involving a cathinone was due to the presence of manganese in poorly synthesized, dirty MCAT reacted with KMnO2. Manganese is, in fact, a nasty dopaminergic neurotoxin, causing progressively worsening Parkinsonian-like symptoms if ingested chronically. That being said, since MCAT is so close in structure to methamphetamine, I assume that it would still be a little more toxic than either regular (d)-amphetamine or regular (S)-cathinone. The toxicology of mephedrone (4M-MCAT) is anyone's guess.

What prodrug of MCAT did you take?
 
I haven't taken MCat or a prodrug of it. I had seen data that put the neurotoxicity of MCat on a par with Methamphetamine, which the chap I'm talking with describes as "insanely neurotoixic". He is trying to educate me as to why methylating methcathinone at position 4 dramatically reduces the neurotoxicity. Basically Mcat is supposedly very neurotoxic but 4MMCat is not. I was hoping for a varification (and preferably expansion) of his explanation. :)
 
From wikipedia: -

Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration.[10][11] High doses of methamphetamine produce losses in several markers of brain dopamine and serotonin neurons. Dopamine and serotonin concentrations, dopamine and 5HT uptake sites, and tyrosine and tryptophan hydroxylase activities are reduced after the administration of methamphetamine. It has been proposed that dopamine plays a role in methamphetamine induced neurotoxicity because experiments which reduce dopamine production or block the release of dopamine decrease the toxic effects of methamphetamine administration. When dopamine breaks down it produces reactive oxygen species such as hydrogen peroxide. It is likely that the oxidative stress that occurs after taking methamphetamine mediates its neurotoxicity. [12] It has been demonstrated that a high ambient temperature increases the neurotoxic effects of methamphetamine.[13]
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http://www.emedicine.com/EMERG/topic859.htm

I apologise about the pro drug reference, I was under the ill informed impression that a substance I had taken was metabolised into Mcat in the body, it isn't so however.

I have however taken methamphetamine, and the stimulant psychosis that follows is indicative of a certain mechanism of brain damage, I can't unfortunately find the article right now, but the basic premise was that it was due to dopamine depletion and the subsequent messaging functions of that neurotransmitter being disrupted, serotonin also came into play.

Despite doing vast amounts of mephedrone at a time I have never noticed a psychotic or hallucinogenic state emerging from binging, at worse I had serotonin depletion resulting in affected mood, but I didn't have the lethargy characteristic of dopamine depletion.

I would assume that there is a vast difference in mechanism and high of both drugs, and to declare the two to have similar neurotoxic effects is flawed, look at heavy meth cat users compared to heavy 4-methylmethcat users and you will see a fairly clear difference.

Edit = To clarify, I referred to methamp as being heavily neurotoxic, as opposed to methcat, methcat has lower neurotransmitter release and thus (in theory) lower neurotoxicity.
 
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It's my understanding that MMCAT has a much higher affinity for 5HT2b and as such is quite dangerous for the heart.

MCAT itself seems fairly benign OTOH.
 
Ham-milton said:
It's my understanding that MMCAT has a much higher affinity for 5HT2b and as such is quite dangerous for the heart.

MCAT itself seems fairly benign OTOH.
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IME that's true. Of course it's highly subjective, but I've experienced slight heart problems after using 4-MMCAT unlike anything else I've experienced with stimulants. That really scared me off.
Somehow I think great care should be taken about using 4-MMCAT as we don't understand the method of action. And as Jamshyd says, compared to 4-substituated amphetamines it doesn't look too good.
 
4-methyl > 4-methoxy > 4-methylthio, though.

That's only relevant for DA and SE releasers, though. DARIs it's irrelevant.
 
Or is it? Increased levels of DA seem like it might be a problem regardless of if it's being released or just not being taken back up.
 
While the 5HT2B agonism is a cause for concern, there are multiple other drugs with decent 5HT2B agonism, MDMA and MDA for example, these drugs have a very long history of abuse, and I don't recall seeing many connections between them and cystic fibrosis.
If you recall Fenfluramine, it took long periods of constant daily use to cause heart damage, although that statement could be misleading as the condition takes a while to develop.

Of course it's highly subjective, but I've experienced slight heart problems after using 4-MMCAT unlike anything else I've experienced with stimulants. That really scared me off.
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What sort of time period did the problems emerge over? I am fairly sure the condition (cardiac fibrosis) takes a while to develop and show symptons.
Resveratrol has been shown to slow development of the condition.
 
Well, I did about 200 mgs divided in four doses overnight with a few glasses of wine on the side. I was feeling great and had no greater side effects during the night. Then when I woke up the next morning after 4-5 hours of sleep my heart was beating irregular and if I took a deep breath it would hurt in the cardiovascular region. This irregular heartrate and sporadic pain continued for approximately 40 hours or so. I had to sleep twice before it went away and during the period of time I felt very uncomfortable when I got excited over something.

In retrospective I probably should've gone to see a doctor, but fortunately I pulled through without greater trouble.
I haven't touched it ever since.
 
the bad thing is if it does cause cardiac fibrosis, or proliferation of cellular growth on the cardiac valves no one is going to know for a while..

The acute cardiac action is probably due to adrenergic activity possibly of the metabolite paramethyl ephedrine/pseudoephedrine.

It seems in my opinion very likely that the substance will prove neurotoxic also.

Either way I suggest leaving it well alone until plenty of other intrepid guinea pigs have tasted it, selfish yes, but sensible.
 
Yeah, I wouldn't rush out and consume any 4-substituted amphetamine without a long-established safety profile. Perhaps I would try 4-fluoroamphetamine if it were available and more common, but I still wouldn't want to use it frequently. Any other substituent is just a tad too sketchy in my book. I don't think I'd take an amphetaminergic compound with serotonergic effects, period (unless it was a pure 5-HT2A agonist, not a SERT substrate).
 
Really? It's something I really want to try, but haven't yet (just bunk meth-y pills, no more!). Seems like something that can have value in lower doses.
 
It seems in my opinion very likely that the substance will prove neurotoxic also.

Either way I suggest leaving it well alone until plenty of other intrepid guinea pigs have tasted it, selfish yes, but sensible.
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Could you elaborate on why you have formed this opinion?

Plenty of intrepid guinea pigs have tried it, it was an ingredient in the Neorganics, and it is commonly sold by various legal high vendors in the UK, I have known people take crazy doses, so any information you can give regarding toxicity/possible toxicity could potentially be very valuable.

I have never seen anyone complain of any nasty side effects, and generally the chemical is very well received, would the neurotoxicity be apparent in any form of comedown or would it be an ongoing accumulative process?
 
IlostaMadge said:
Could you elaborate on why you have formed this opinion?

Plenty of intrepid guinea pigs have tried it, it was an ingredient in the Neorganics, and it is commonly sold by various legal high vendors in the UK, I have known people take crazy doses, so any information you can give regarding toxicity/possible toxicity could potentially be very valuable.

I have never seen anyone complain of any nasty side effects, and generally the chemical is very well received, would the neurotoxicity be apparent in any form of comedown or would it be an ongoing accumulative process?
Click to expand...

it took 10 years for the neurotoxicity concerns of MDMA to be discovered, and that was a subsance that was being pretty heavily investigated by the scientific community Methyl methcathinone is not being investigated as far as I know. the comedown effects of MDMA does not really have anything to do with the neurotoxicity.

methyl methcathinone is an unknown, methcathinone is neurotoxic so given methyl methcathinone probably works in the same way I would be very surprised if it wasn't neurotoxic also. so the intrepid guinea pigs might be pruning their neurons and we will not know for a bit.

http://jpet.aspetjournals.org/cgi/content/abstract/279/2/1043
 
The neurotoxic effects of MDMA are somewhat evident, I was under the impression that the hallucinations produced on the comedown from the drug were indicative of 5HT presynaptic neuron damage, I may be grossly misinformed here.

As for methcat vs 4-methyl methcat, in my subjective opinion it is far less dopaminergenic, whilst methcathinone, methamphetamine and other dopamine cascading stimulants carry a period of lethargy and a marked hallucinatory state after large binges (due to dopamine depletion), mephedrone does not, it carries some depression and mood alteration that I would attribute to low levels of 5HT (in a similar way but not as drastic as MDMA "mid week blues").

Generally with heavy stimulant abuse the psychotic delerium like state that ensues is indicative of a depletion of dopamine leading to it's messenger functions becoming disrupted, despite vast amounts of mephedrone being taken in a short space of time, this state does not occur.

I know this is all heavily subjective, and as with any unresearched chemical, caution and moderation should be exercised, but I wanted to give a few opinions and get feedback on them, I am not stating these claims as fact, merely asking to get opinions from more informed people than I.
 
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