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d-METH dopamine toxicity>>>d-AMPH? Orly, why?

P A

P A

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I'm sure this has been dealt with before, so I apologize for any redundancy, but what's with the deal with this popular meth-hate among amateur pharmacology enthusiasts? I hear talk of substantially more egregious toxicity than dextroamphetamine at equivalent doses and see little substantiation, apart from d-methamphetamine's comparatively higher [though still meager] affinity for the serotonin transporter.

Aside from the moderately increased risk of hyperthermia at equipotent dosages [via downstream postsynaptic 5-HT2A agonism], what relevance does meth's still-weak serotonergic properties actually have? Or is this just another oft-repeated myth of 'intelligent' drug culture?

(Kinda relevant: My interest stems from the fact that I plan on replacing my p.r.n. 20mg Dextrostat dose with a 10mg tablet of Desoxyn for regular use - are my concerns even justified at such a low dose? If so, why?)
 
Kinda hard to believe 10 mgs would cause problems. People routinely IV 10-30 times that much. While the dangers at that level are obvious, even without much knowledge of pharmacology, 10 mgs should be fine. So long as you keep the dose at that level that is. There's something about meth that seems to lead to "if one is good twenty would be better" type thinking.
 
even without much knowledge of pharmacology, 10 mgs should be fine
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Unfortunately, as modern psychiatry [and psychopharmacology/neurotoxicology in general] was forced to find out the hard way, the chemical interactions that comprise your conscious experience, and the wide variety of drugs and poisons that can significantly fuck them up, are not subject to the otherwise sturdy principles of basic human common sense. Though I agree wholeheartedly with you, I need more rigorous confirmation than "eh it's a low dose, probably no problem" reasoning on this one: my midbrain and right frontal lobe are already fucked up enough as it is, and I don't feel like complicating matters by introducing putatively potent central dopaminergic neurotoxins.

I already take unnecessarily large antioxidant/antihyperthermic precautions for my current dextroamphetamine use (high dose glutathione boosters/donors, acetylcarnitine hydrochloride, hypothermics), so I'd likely be more-than-covered on the issue. I'm just more curious than anything.
 
Substantiation comes from animal studies, methamphetamine is much stronger of a neurotoxin than amphetamine in mice, rats and primates. Methamphetamine is a neurotoxin standard.

The hypothermia produced by serotonin release along with oxidative metabolism through MAO-B causes monoamines to redox cycle and destroy mitochondrial DNA/induce apoptosis. This is much less present in d-AMP (though at very high doses/chronic doses it will still produce toxicity in some species for dopaminergic neurons).
 
The hypothermia produced by serotonin release along with oxidative metabolism through MAO-B causes monoamines to redox cycle and destroy mitochondrial DNA/induce apoptosis
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I'm aware. And I think the word you're looking for is hyperthermic, yeah?

But like I asked, is that really it? Such a meager pharmacologic difference doesn't sound like it would have any relevance to the average low/moderate-dose therapeutic user [even without my relatively extreme protective measures], though there appears to be quite a bit of undue concern. I'm just trying to find out whether any of it is actually warranted.
 
If it were quite bad, even at low doses, it would lose it's licence (anybody remember thalidomide/genetic faults or COX inhibitors/heart attacks). As long as you don't reach the point of completely depleting neurones of their neurotransmitters with larger doses, any damage that does occur should be minimal (or else they wouldn't be allowed to prescribe it!)
 
In low (i.e. therapeutic) doses, d-amp is hypothermic anyway. So unless you're going crazy with the dosing, additional hypothermics probably aren't such a great idea.
 
In low (i.e. therapeutic) doses, d-amp is hypothermic anyway. So unless you're going crazy with the dosing, additional hypothermics probably aren't such a great idea.
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True that.

I was referring to more 'prophylactic' hypothermics like 5-HT2A antagonists in my post, but yeah, that's definitely good to note. Needless to say, I've abandoned their use, as I see no need for serious concern nor meticulous damage control in the intermittent <15mg doses to which I'm partial.
 
P A said:
Unfortunately, as modern psychiatry [and psychopharmacology/neurotoxicology in general] was forced to find out the hard way, the chemical interactions that comprise your conscious experience, and the wide variety of drugs and poisons that can significantly fuck them up, are not subject to the otherwise sturdy principles of basic human common sense. Though I agree wholeheartedly with you, I need more rigorous confirmation than "eh it's a low dose, probably no problem" reasoning on this one: my midbrain and right frontal lobe are already fucked up enough as it is, and I don't feel like complicating matters by introducing putatively potent central dopaminergic neurotoxins.

I already take unnecessarily large antioxidant/antihyperthermic precautions for my current dextroamphetamine use (high dose glutathione boosters/donors, acetylcarnitine hydrochloride, hypothermics), so I'd likely be more-than-covered on the issue. I'm just more curious than anything.
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Could you name the antihypertheric/hypothermic substance you speak of as ive been looking for some. Im curious about the glutathione donors/boosters as well.
 
Most of the text from about 10 years ago say Amphetamine and Methamphetamine release the same amount of Dopamine, but I have always been sceptical of this, after trying both, and this article shows they are very different:

"Amphetamine and Methamphetamine differentially affect Dopamine Transporters in vitro and in vivo" (2009) J. Biol. Chem.

This article shows that Methamphetamine releases up to 5 times more Dopamine than Amphetamine.

And the extra Dopamine can increase Serotonin release by activating D2 receptors, explaining why they feel so different.
 
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