which substances are Neurotoxic?

[BilZ0r]

Well I've seen people refer to tardive dyskinesia as a neurotoxic event, just because it can be permanent.

 

[trypt]

I also found an interesting study showing DXO (a metabolite of DXM) prevents the neurotoxic effects of MDMA: http://www.erowid.org/references/refs_view.php?ID=571

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[BilZ0r]

Body temperature? Antioxidant? Gotta be one of those...

 

[VelocideX]

Well I don't think you'll find that SSRIs just like... shift depressed peoples moods up 1 level, so that the bad times are okay, the okay times a good, and the good times are great.... Usually, it just means that the unbelievabley bad times are managable...

However SSRIs act, its probably secondary to the serotonin uptake inhibition... some peopl argue that its neurogenesis, though I don't think it is.

Some experiemnts report that MAOIs have a therapeutic lag, but others don't.... I personally suspect they don't (though I've never taken one clinically). Velocide, anything to add?

Moclobemide certainly has a lag time, though its not as long as the SSRIs (probably because of its dual 5-HT/NE action; drugs which act on both appear to have short lag times e.g. venlafaxine).

Neurogenesis has been shown to be required for the antidepressant effect hasn't it? There's studies where irradiation of the hippocampus to stop neurogenesis blocks the antidepressant effect of all the antidepressants.

AFAIK the irreversible MAOIs have an initial stimulant-like response which fades over a few days... the antidepressant effect manifests after a week to two weeks then keeps increasing to its maximum over the period of another few weeks.

I dont think the SSRIs are merely mood enhancers; I believe they have some fundamental effect on cognition processes. I had clinical depression, at times quite severe, for years, and it took me years toeven admit that I had it. I kept blaming it on circumstances time after time. Even when I admitted I had it, nothing really worked. I rationally knew that things in my life were great, and I had no reason to be depressed, but nevertheless I felt like shit... I'd feel so upset and felt like bursting into tears but I knew I had no reason too. Since being on moclobemide my emotions are back to top notch, but my thinking has shifted too. I am more self-confident, and more relaxed. Is this a function of my new-found emotional set, or is there some other mechanism at work?

 

[BilZ0r]

Neurogenesis has been shown to be required for the antidepressant effect hasn't it?

No... well the effects of antidepressants, or of SSRIs specifically?

I definatly don't think SSRIs are mood enchancers...

 

[VelocideX]

I'm kinda busy atm, but take a look at http://mentalhealth.about.com/cs/psychopharmacology/a/neurogenesis.htm

To find out if the observed neurogenesis is involved in antidepressants’ mechanism-of-action, Rene Hen, Ph.D and colleagues selectively targeted the hippocampus with x-rays to kill proliferating cells. This reduced neurogenesis by 85 percent. Antidepressants had no effect on anxiety and depression-related behaviors in the irradiated mice. For example, fluoxetine failed to improve grooming behavior, as it normally does, in animals whose behavior had deteriorated following chronic unpredictable stress. Evidence suggested that this could not be attributed to other effects of x-rays.

also:

By knocking out the gene that codes for a key subtype of serotonin receptor (5-HT1A), the researchers created a strain of "knockout" mice that as adults show anxiety-related traits, such as a reluctance to begin eating in a novel environment. While unaffected by chronic treatment with the SSRI fluoxetine, the knockout mice became less anxious after chronic treatment with tricyclic antidepressants, which act via another neurotransmitter, norepinephrine, suggesting an independent molecular pathway.

While chronic fluoxetine treatment doubled the number of new hippocampal neurons in normal mice, it had no effect in the knockout mice. The tricyclic imipramine boosted neurogenesis in both types of mice, indicating that the serotonin 1A receptor is required for neurogenesis induced by fluoxetine, but not imipramine. Chronic treatment with a serotonin 1A-selective drug confirmed that activating the serotonin 1A receptor is sufficient to spur cell proliferation.

I'm sure you could find the study easily on pubmed

 

[BilZ0r]

Yeah, but some other anti-depressants have no effect on neurogenesis.

 

[VelocideX]

Such as?

 

[BilZ0r]

Well seeing as FUCKING SCIENCE DIRECT IS FUCKING BROKEN PEICE OF SHIT.... the only example I can remember is trans-cranial electromagnetic stimulation...

There's also evidence that decreased neurogenesis DOESN'T lead to depression.

...and I don't think anyones ever looked to see whether MAOIs effect hippocampal neurogenesis.

 

[VelocideX]

Don't people with depression usually show reduced hippocampus volumes though?

 

[BilZ0r]

Yeah but there a plenty of other ways to explain that... my main one would be secondary to high levels of circulating corticosterone...

 

[/navarone/]

Methamphetamine byproducts...

Something i am worried and curious about is the level of neurotoxicity of byproducts from the synthesis of methamphetamine such as:

1) Iodo-ephedrine
2) Phenyl-2-Propanone
3) Propiophenone

The substances above are commonly found all-toghether in a percentage between 1-6% in street methamphetamine.
They are byproducts formed from the reaction of (pseudo)ephedrine with hydriodic acid and red phosphorus (wich is the synthesys method almost every cook uses to synthetise methamphetamine since its relatively easy to obtain the reagents)
Theese byproducts are pretty hard to separate from the methamphetamine. Theese ones dont get separated during standard "Acid-Base Extraction". The only laboraory tecniques that are able to separate the toxic byproducts from the meth are steam distillation of the methampetamine freebase and recrystallization. Both tecniques are tricky to perform due to the need of advanced laboratory skills/knowledge and/or the need of serious lab apparatuses. this is why most meth cooks dont even bother to perform such purification processes sincea well performed Acid-Base extraction already gives optically clear crystals.
On the "Bees website" i read more than once that iodoephedrine and many other methamphetamine byproducts are highly toxic for the human body. I tired to search for more detailed information about the type and level of toxicity theese substances may give.
Unfortunately i came out with nothing....i also tried to search on google and altavista but, so far, no info on the specific toxicity of the above substances.

I already red an article long time ago stating that many amphetaminic substances that are very similar to commonly used phenylethylamines showed many bad qualities from the toxicity point of view,futhrmore it said that this is the main reason why amphetaminic compounds suitable for human consumption wasnt that easy. This article amde me a bit paranoid about different amphetamines.
One weird thing is that halo-amphetamine such as chloro/bromo-ephedrine where used not much time ago in many antistaminic pharmaceuticals. The reason why they got removed from commerce was because theese substances where way easier to convert to methamphetamine than converting pseudoephedrine to meth, and since the all had the same wanted effects of pseudoephedrine so the DEA managed to ban theese. No relevant toxicity was found in chloro/bromo-ephedrine otherwise they wouldnt have been put on the market.
Even if chloro and bromo ephedrine where used in pharmaceuticals, iodo and fluoro isomers of ephedrine never appeared in the pharmaceutical market.
I supposed this was due to the higher toxicity of iodine and fluorine that chlorine and bromine but then i remembered that iodine and fluorine are used in many drugs/pharmaceuticals such as 2C-I,2C-F, many bezodiazepines and other pharmaceuticals. this confirmed that the presence of iodine or fluorine in a drug doesnt necessarely mean that the drug is highly toxic.
Anybody here might know a bit more about the toxicity and the dangers of the 3 substances listed above?

Some info would be very apreciated by me and (i guess) by many other tweakers.

-Navarone-

 

[sk8punk151]

Based by my opinion, I'd have to say some of the 2Cs are most likely neurotoxic. Something that gives me lasting hallucinations for months after use isn't good at all (2C-I)

 

[K'dOUTinAZ]

I have a feeling that 4-Mar may be neurotoxic but there isn't much data on that drug just yet.

 

[VelocideX]

Based by my opinion, I'd have to say some of the 2Cs are most likely neurotoxic. Something that gives me lasting hallucinations for months after use isn't good at all (2C-I)

HPPD may, strangely, not meet the definition of neurotoxicity...

 

[BilZ0r]

4-Mar? Like dimethylaminorex? It's not neurotoxic, some of my collegues did that work.

 

[VelocideX]

Eh, if only 4-MAR was legal.

 

[/navarone/]

4-Mar? Like dimethylaminorex? It's not neurotoxic, some of my collegues did that work.

4-MAR is methylaminorex and not dimethylaminorex.
Anyway I think there isnt much neurotoxic difference between the 2.

BTW I just noticed that methylaminorex is actually an amphetamine.
Even if the structure doesnt immediately look like an amphetaminic substance, if you look more carefully yu'll see that methylaminorex contains the amphetamine chain even if its streched to a ring by the methoxyamine molecule.

As you can see after the benzene ring there is a propane chain with a nitrogen attached to the second carbon.That is amphetamine and the presence of that group classifies methylaminorex under the amphetamine family from the pharmaceutical point of view.
In fact if you manage to remove the methoxyamine group you'll get amphetamine

Later on on Erowid I found an article regarding the synthesis of methylaminorex saying that the main ingredient is Phenylpropanolamine wich is exactly amphetamine with a hydroxy(OH) group attached to the 7th carbon of the molecule, its exactly like ephedrine without the methyl group attached to the amino part.
With some reagents it is possible to convert phenylpropanolamine to methylaminorex by connecting the oxygen and the nitrogen with a methylamine group.

Could this mean that methylaminorex might preserv some amphetamine toxicity propeties?

What was written above is just an idea I had, is methylaminorex really considered an amphetamine compound?

 

[K'dOUTinAZ]

They are pretty similar aren't they? I find the effects pretty similar also. But back in my tweeking days I would have much rather prefered methylamphetamine over methylaminorex. Bliz0r, what do you know of dimethylaminorex? I haven't heard of this one before, is it a weaker or more potent version of 4-MAR? Ever try it before?

 

[BilZ0r]

I know jack didly squat... I've only ever read that article as the PhD thesis that it was finally submited as... I should have a look that single article.