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Amphetamine Neurotoxicity and Tolerance Reduction/Prevention II

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chaultistic said:
I'm a little confused, I wasn't talking about methamphetamine. I was talking about regular amphetamine mix switched back and forth between cocaine/mph. Does levo/dextroamphetamine itself cause redistribution of VMAT?

*edit* I'm not very savvy about all this stuff, so bear with me on my questions.
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No problem. Yes, levo/dextroamphetamine should in theory also cause redistribution of VMAT. Amphetamine and methamphetamine act virtually the same in the brain, besides slightly different affinities for the different transporters and the latter being more neurotoxic; so, the study that epsilon alpha cited should apply to amphetamine as well.
If it was my comment about being a guinea pig that confused you, all I was saying was 'better the devil you know' and such :P


By the way, anyone have an idea of what effect phosphatidylserine might have on amph neurotoxicity? It seems to be protective against NDMA-excitotoxicity related pathways such as ischemic cell death, but on the other hand D-serine itself potentiates excitotoxicity so I'm hesitant to add phosphatidylserine to my stack.
Edit: Nevermind, the supplement version is phosphatidyl-L-serine :P
 
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Are there any ways to decrease NE augmentation and increase the serotonin and dopamine release with basic amphetamine?
 
Renz Envy said:
Are there any ways to decrease NE augmentation and increase the serotonin and dopamine release with basic amphetamine?
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Wouldn't Dextroamphetamine be the key here? I think I've read somewhere that is has very little effect on NE, and much greater effect on DA, not sure about SERT, but possibly.
 
chaultistic said:
Wouldn't Dextroamphetamine be the key here? I think I've read somewhere that is has very little effect on NE, and much greater effect on DA, not sure about SERT, but possibly.
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'Basic amphetamine' (though a loose term) is what is meant by dextroamphetamine, since it has to be an isomer and 'dextro-' is the active one.
 
chaultistic said:
Wouldn't Dextroamphetamine be the key here? I think I've read somewhere that is has very little effect on NE, and much greater effect on DA, not sure about SERT, but possibly.
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I do mean dextro amphetamine.
D-amp does have quite the potency on NE compared to its meth brother.
 
I agree that antioxidants very beneficial

alfa lipioc acid and L-glutamin would be two most effective in my books.

also neurotoxicity of amphetamine may need some revision. result of neurotoxicity is always a loos of some particular type of neuronal cells, if something toxic to cells then cells are gone.

Like in case with MDMA it is believed that serotonegic neurons are lost. I would like to see similar information regarding amphetamine.

In one case described in New Concepts of Psychostimulants Induced Neurotoxicity 2009 four chronic amph users brains been examined on postmortem - no any degeneration been reported.

I think that kind of hard evidence may be crucial in establishing of concept of neurotoxicity, similar evidence been demonstrated in many cases of neurodegenerative diseases, but not in case of amphetamin as far as I know.
 
MaxTTR said:
I agree that antioxidants very beneficial

alfa lipioc acid and L-glutamin would be two most effective in my books.

also neurotoxicity of amphetamine may need some revision. result of neurotoxicity is always a loos of some particular type of neuronal cells, if something toxic to cells then cells are gone.

Like in case with MDMA it is believed that serotonegic neurons are lost. I would like to see similar information regarding amphetamine.

In one case described in New Concepts of Psychostimulants Induced Neurotoxicity 2009 four chronic amph users brains been examined on postmortem - no any degeneration been reported.

I think that kind of hard evidence may be crucial in establishing of concept of neurotoxicity, similar evidence been demonstrated in many cases of neurodegenerative diseases, but not in case of amphetamin as far as I know.
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From what I've seen so far, gross cell death isn't often seen but diffuse damage and inflammation is. Not to mention potential "wiring" problems.
Still climbing midterm mountain...
 
Epsilon Alpha said:
From what I've seen so far, gross cell death isn't often seen but diffuse damage and inflammation is. Not to mention potential "wiring" problems.
Still climbing midterm mountain...
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IIRC in the case of MDMA the loss of 5-HT cell bodies is not observed, but rather axons are destroyed, while in the case of (meth)amp the entire DA neuron is lost. I'm not 100% on this though.

MaxTTR, that's very interesting, and if you could provide a link to that source I'd be grateful. That seems to further evince what appears to be the case with most (human, non-meth) amph users: that no significant damage occurs. One study I saw found that high-dependence amphetamine users were cognitively impaired, while low-dependence users were indistinguishable from controls besides that they scored higher in verbal memory. The study was very well controlled and such. And as far as the high dependence users go, it's hard to say whether the impairment they showed was the result of neurotoxicity or simply downregulation.
 
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What about monoamine transporter activators?
Apigenin, Luteolin and IMO few other flavonoids seems to be MaT activators.
Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt.
Zhao G, Qin GW, Wang J, Chu WJ, Guo LH.
Source

Cell Star Bio-Technologies Co., Limited, Shanghai, PR China.
Abstract

Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator. Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin. Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators. Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter. Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity.
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http://www.ncbi.nlm.nih.gov/pubmed/19815045

Bioorg Med Chem. 2010 Nov 15;18(22):7842-8. Epub 2010 Sep 25.
Discovery and synthesis of novel luteolin derivatives as DAT agonists.
Zhang J, Liu X, Lei X, Wang L, Guo L, Zhao G, Lin G.
Source

Department of Medicinal Chemistry, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China. [email protected]
Abstract

Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizing constructed Chinese hamster ovary (CHO) cell lines stably expressing rat DAT. Biological screening results demonstrated that luteolin derivatives 1d, 1e, and 4c carry great DAT agonistic potency (EC(50)=0.046, 0.869, and 1.375μM, respectively) compared with luteolin 8 (EC(50)=1.45±0.29μM). Luteolin derivative 1d, notably, exhibited a 32-fold-higher DAT agonistic potency than luteolin. These luteolin derivatives represent a novel DAT agonist class, from which lead compounds useful for exploration of additional novel DAT agonists could be drawn.
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http://www.ncbi.nlm.nih.gov/pubmed/20971650

Meal rich in parsleys, broccoli, apples, oranges and many other vegetables and fruits was able to shutdown compltetly high doses of 2-DPMP, Ethylphenidate or 6-APB.

I thinking about taking NDRI(methylphenidate or ethylphenidate) during the day and eating really alot fruits in the evening. How it would affect neurotoxicity?
 
bremes said:
I thinking about taking NDRI(methylphenidate or ethylphenidate) during the day and eating really alot fruits in the evening. How it would affect neurotoxicity?
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It wouldn't, with NDRI's there is no neurotoxicity to affect. They actually block amphetamine neurotoxicity. I think some studies suggest MPH/cocaine promote apoptosis, but I don't think it occurs in relevant doses.
 
Then why people are using amph instead of NDRI's? You think even heavy use of NDRI shouldn't lead to any toxicity?

How would this MaT agonists affect amphetamine neurotoxicity?
 
atrollappears said:
It wouldn't, with NDRI's there is no neurotoxicity to affect. They actually block amphetamine neurotoxicity. I think some studies suggest MPH/cocaine promote apoptosis, but I don't think it occurs in relevant doses.
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Would you say the apoptosis from cocaine/mph is worst than the neurotoxicity of amph? What doses would you say of MPH or AMPH would cause a low to high amount of toxicity, or apoptosis, would AMPH also cause apoptosis?
 
chaultistic said:
Would you say the apoptosis from cocaine/mph is worst than the neurotoxicity of amph? What doses would you say of MPH or AMPH would cause a low to high amount of toxicity, or apoptosis, would AMPH also cause apoptosis?
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Cocaine & MPH are NDRIs, what atrollappears was saying is that they, unlike DRAs & amphetamines, are not known to be neurotoxic. In-fact I have read evidence of them being quite neuroprotective.

...

It is interesting that VMAT is normal in methamphetamine users. I wonder what a compound that is selective for release at VMAT but acts as a DRI at MAT would do, if possible.
 
New.Concepts.of.Psychostimulants.Induced.Neurotoxi city.2009

atrollappears said:
IIRC in the case of MDMA the loss of 5-HT cell bodies is not observed, but rather axons are destroyed, while in the case of (meth)amp the entire DA neuron is lost. I'm not 100% on this though.

MaxTTR, that's very interesting, and if you could provide a link to that source I'd be grateful. That seems to further evince what appears to be the case with most (human, non-meth) amph users: that no significant damage occurs. One study I saw found that high-dependence amphetamine users were cognitively impaired, while low-dependence users were indistinguishable from controls besides that they scored higher in verbal memory. The study was very well controlled and such. And as far as the high dependence users go, it's hard to say whether the impairment they showed was the result of neurotoxicity or simply downregulation.
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here it is, this review is a real milestone in this direction.

http://www.datafilehost.com/download-023bc943.html

more correct would be to call it as alteration of brain function.
 
Cocaine & MPH are NDRIs, what atrollappears was saying is that they, unlike DRAs & amphetamines, are not known to be neurotoxic. In-fact I have read evidence of them being quite neuroprotective.
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Do you have any paper about it?
 
bremes said:
Do you have any paper about it?
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They're neuroprotective in that they block AMPH or MPTP neurotoxicity. I don't know how useful that is for people or rats who are not being exposed to MPTP or large doses of AMPH. This is pretty much common knowledge; it's the same principle that makes SSRIs protective against MDMA neurotoxicity.
 
atrollappears said:
They're neuroprotective in that they block AMPH or MPTP neurotoxicity. I don't know how useful that is for people or rats who are not being exposed to MPTP or large doses of AMPH. This is pretty much common knowledge; it's the same principle that makes SSRIs protective against MDMA neurotoxicity.
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I think I've read that chronic lifetime cocaine users also have lower overall instances of alzheimer's, etc.
 
Nagelfar said:
I think I've read that chronic lifetime cocaine users also have lower overall instances of alzheimer's, etc.
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Hmm so then NDRIs may have some general neuroprotective effects, but that doesn't prove a cause-effect relationship with NDRI action or even cocaine.
 
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