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Once and for all: Dextroamphetamine vs. dextromethamphetamine

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rae26

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1. Are there any actual differences in CNS stimulant effects between dextroamphetamine (Dexedrine) and dextromethamphetamine (Desoxyn), except for the increased potency per mg of meth (due to increased lipid solubility)? Is it true that Desoxyn gives clearer thoughts and more "control" and at the same time less side effects or is that just placebo?

2. Why is meth neurotoxic when un-methylated amphetamine does not seem to be?

3. Is there a lower limit of blood plasma concentration for methamphetamine neurotoxicity? Is 20-60 ng/mL completely safe as indicated here or did I get something wrong?

Thanks.
 
I can tell you off the bat that meth has more affinity for Serotonin than amphetamine. I believe Bilzor posted factual data on this a long time ago on this forum. The other main difference is the one you mention - the methyl group leads to greater solubility. As for which is more effective, it is a matter of opinion. I would personally go for Dexedrine over Desoxyn (or even IV crystal) any time.

As for #2, I have a feeling that no one really knows yet - although I could be wrong.

I have no idea about #3.
 
I'm pretty sure that the neurotoxicity is pretty much due to the greater potency. It makes sense that the drug that hits harder, and faster would damage dopamine neurons faster.
 
#2 is to do with the serotonin efflux and the fact that the serotonogic neurones hoover up dopamine a la MDMA

Because of it's serotonogic activity, there's not going to be a 'safe' level fot methamphetamine, just a dose that causes less damage
 
Thank you for your input so far.

As for the numbers it's of course supposed to be 20-60 µg/dL (200-600 ng/mL). Although I'm still not sure that by "toxicity" they mean "neurotoxicity" in the HSDB.
 
is it really true that AMP is not neurotoxic whereas METH is? I have the feeling that both are neurotoxic but that METH is just more effective as a neurotoxin.
 
i've often wondered...

just what is meant by "neurotoxic"; there are a whole lot of structures and places in that universe of grey matter. We should be able to stste "specific neurotoxicity", but that would be a lot tougher to figure out. I guess "neurotoxicity" is defined as "damage to certain neurons that efffect certain behavioral (physiological) traits, govered by the CNS.
That AMP is used in the clinic for affective disorders, instead of meth, does tell us something. It must mean that AMP has a safer toxicity profile (CNS and PNS)
 
Technically, extremely high doses of d-amphetamine are neurotoxic as well. The neurotoxic dose threshold for methamphetamine is far lower, however. In addition, as F&B already pointed out, methamphetamine elicits MDMA-esque neurotoxicity, whereas d-amphetamine has no serotonergic effects. At normal clinical doses, Dexedrine seems to be quite safe and has been used by countless humans for almost 70 years. I'm not entirely sure if the same can be said of methamphetamine. As for the real sequelae of animal models of neurotoxicity--thus far, they are not well known. From a cellular perspective, I believe the most consistent finding is a change in dopaminergic nerve terminal morphology and a reduction in synaptic DAT proteins. Only in extraordinary high doses (say, 10+ mg/kg) does one begin to encounter true apoptosis of dopamine neurons.
 
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I see. But now that Desoxyn is used therapeutically against narcolepsy and ADHD at dosages of around 10-20 mg, does this mean that such low amounts are below the threshold of neurotoxicity; possibly even that of serotonergic-induced neurotoxicity?

Edit: Also, to what extent may meth neurotoxicity be counteracted with antioxidants, i.e. ascorbic acid? Completely or just partly?
 
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^ This might be true, but in my opinion it is more likely that this is the case of allowing pharma companies to make money marketting toxic substances. After all, in a world where AIDS drugs are prescribed regularly, I am not surprised that meth toxicity is overlooked.
 
I doubt that serotonergic effects would even occur at 20-25mg per day of Desoxyn. Now, I still believe that regular amphetamine is "healthier" (or far less damaging, depending on your point of view) than methamphetamine.
 
^ The IC50 for SERT with meth is at a level that you are approaching with clinical doses, so I'd imagine that even at 20-25mg doses it elicits neurotoxicity.

There are plenty of well dodgy drugs still prescribed for clinical use, it's just that either a)there are no other decent alternatives or b) pharm companies put pressure on to be able to prescribe said compounds

After all, how good for your body do you think long term corticosteroid treatment is?
 
I saw this program on TV where it said that the pharm companies were only presenting the positive evidence in favor of the drugs and deciding to withdraw anything that could tarnish their chances. This is the inverse (vice versa) of the propaganda exercized by LE on compounds judged to be abusable.
 
All right, it seems that neurotoxicity at some level or another is inevitable with methamphetamine use. It also appears, looking at what's been said in this thread and others, that many of the people here prefer Dexedrine (as opposed to racemic amphetamine formulations like Adderall, I would guess) with regard to not only its health benefits but also the CNS stimulant effects themselves. But if this is the general idea, then why all this talk about Desoxyn being the "ultimate" ADHD medication?

The reason I am asking all this is because I am about to go on an ADHD examination and I want to know what medication I should try to get.
 
Old text used to denote that dex was a carcinogen and caused petechial cerebral hemorrhages.

I can imagine about any stimulant in too high of doses can cause STROKE! Especially some the direct/indirect acting agonists like ephedrine and mephentermine. Old folks I know swear that mephentermine (Wyamine inhalers) used to be quite potent. I only wonder if the PNS effects are less than ephedrine. I know phentermine is mildly affective. I read some place they used to (maybe still do) give astronauts (specifically John Glenn) mephentermine and dexedrine (or benzedrine) pills in their first aid kits. I can imagine some of the reasons for this.
 
Also wanted add isn't formaldehyde neurotoxic? I know it is toxic. Is there maybe some demethylation happening in the synapse/neuron possibly producing methyl- free radicals?
 
I tHink...

The question of desoxyn (meth) being in the clinic for narcolepsy is that it MUST come on quicker (methylated being more lipid soluble) and last longer (better protected from MAO) than AMP. You can take AMP and wait the 15-20 mins or so to make it to work or school, but when you are narcoleptic and you feel an attack coming on when driving in heavy traffic and can't easily pull off the road for a nap, a quick acting jolt that will last awhile and be strong enough, is what you need. I know, i've driven as a passenger with a long time narcoleptic and saw this effect right before my eyes.
Length of action is also important for the anorexigenic properties of the half-life differences, although one could easily get around this by closer dosing schedules.
My biggest concern is that such dopaminergic compounds as AMP and meth, are structurally related to MPTP. I wonder if the same (or a similar) mechanism is to some extent involved with in the greater neurotoxicity of meth because it is a secondary amine. I know that MPTP is a tertiary amine and easier to get in the "quaternized state" where a charged species is formed that then can't pass out of the cell, which then allows it to turn on an apoptosis signal, but is this the heart of the neurotoxicity mechanism for meth too in spite of it being only a secondary amine?
 
I've certainly never heard of dextroamphetamine being a carcinogen. There was a scare about methylphenidate having the potential to be a carcinogen a year or so ago, but the evidence wasn't exactly compelling and only came from one single nonhuman study (as I recall).

As for the stroke comment, the stimulant most likely to cause stroke / spontaneous cardiac death is cocaine, by far. However, it can happen with amphetamines and ephedrine as well. Obviously, anyone with or predisposed towards cardiac problems (especially ventricular arrhythmia) should stay from all stimulants, period.
 
You can take AMP and wait the 15-20 mins or so to make it to work or school, but when you are narcoleptic and you feel an attack coming on when driving in heavy traffic and can't easily pull off the road for a nap, a quick acting jolt that will last awhile and be strong enough, is what you need.


Oral meth doesn't come on any faster than oral IR amphetamine. I notice that Adderall XR takes an hour or so to notice anything, but there's no difference between IRs and Desoxyn.
 
Here is a little table found while scrounging the net.

stimtable.png


Interesting.
 
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