5 replies to this topic

[InquilineKea]

Okay, the truth is, glutumate is not a *direct* neurotoxin. It's an indirect neurotoxin. It opens up AMPA and NMDA receptors, allowing Calcium ions to rush in. And it's actually the calcium ions that are actually responsible for the neurotoxicity (IIRC, it has something to do with the Calcium getting into the mitochondria and making the mitochondria inner membrane more permeable, making free radical reagants more likely to "leak out and combine").

Now, what piracetam does is "enhance the activity of AMPA receptors". It also increases postsynaptic AMPA receptor density. So then what? I would think that it would result in an increased amount of calcium flux into the postsynaptic cell. And that can cause neurotoxicity.

I know that we don't know everything about piracetam yet, but I'd at least like to get this answered first.

[onetimevisit]

A laymans shot
There is an article that claims that piracetam decrease the permability and density of calcium channels(could not source,anyone find?). This theoretically would allow greater electrophysological activity for a given level of oxidative stress. Holistic evidence exists for this, in that Piracetam significantly attenuates neuradegredational markers following hypoxia(on acute basis). I have seen claims tho that piracetam does increase activity of some Ca+2 channels, this indicates that the protection is only partial, or that a non-functional(math) relationship exisit regarding neuroprotection/neurodegeneration. The location of calcium channels is also very important to determine the tradeoffs.

It is without doubt that Piracetam increase Long Term Potentiation(LTP)(i recommend that all Nootropic user study this and its antithesis). Increased AMP postsynatpic density is an example of this effect, which could be described as cholinergnic(global connectivity).AMP receptors in themseleves dont allow calcium to pass, so that direct route isnt of consequence. However increased AMP receptors increases the proability of depolarisation which increases the flux of calcium. Therefore Increased Long Term Potentiation does have the ability to facilitate excitoxic damage, although this is complex and really requires empirical research to quantify. Increased LTP definitly facilitates some forms of memory, particularly of the crystalized nature. It would be expected that the are some 'costs' to fluid  intelligence, this could cause brain fog and depression. Oxidative stress in the mitochondria is not a speciality of mine, although piracetam does appear to have indirect antioxidant effect.
Really need more research, potential does exist for neurotoxicity

I have not advocated healthy individuals use this substance for nootropic purposes, there appears to be some support for its use in various disorders. By a docotors recommendation, i would have to say.

[outsider]

onetimevisit, on 13 January 2011 - 10:28 AM, said:

A laymans shot
There is an article that claims that piracetam decrease the permability and density of calcium channels(could not source,anyone find?). This theoretically would allow greater electrophysological activity for a given level of oxidative stress. Holistic evidence exists for this, in that Piracetam significantly attenuates neuradegredational markers following hypoxia(on acute basis). I have seen claims tho that piracetam does increase activity of some Ca+2 channels, this indicates that the protection is only partial, or that a non-functional(math) relationship exisit regarding neuroprotection/neurodegeneration. The location of calcium channels is also very important to determine the tradeoffs.

It is without doubt that Piracetam increase Long Term Potentiation(LTP)(i recommend that all Nootropic user study this and its antithesis). Increased AMP postsynatpic density is an example of this effect, which could be described as cholinergnic(global connectivity).AMP receptors in themseleves dont allow calcium to pass, so that direct route isnt of consequence. However increased AMP receptors increases the proability of depolarisation which increases the flux of calcium. Therefore Increased Long Term Potentiation does have the ability to facilitate excitoxic damage, although this is complex and really requires empirical research to quantify. Increased LTP definitly facilitates some forms of memory, particularly of the crystalized nature. It would be expected that the are some 'costs' to fluid  intelligence, this could cause brain fog and depression. Oxidative stress in the mitochondria is not a speciality of mine, although piracetam does appear to have indirect antioxidant effect.
Really need more research, potential does exist for neurotoxicity

I have not advocated healthy individuals use this substance for nootropic purposes, there appears to be some support for its use in various disorders. By a docotors recommendation, i would have to say.

I've just read today that muscarinic stimulation produce LTD (long term depression not LTP) in NMDA.  And LTD seems to be a protection mechanism as stated in a 2010 study on the LTD phenomena.  Looks like nicotinic receptors are more LTP for NMDA but I didn't look too much into it yet.

[kilgoretrout]

Precise definition of "neurotoxic"? People love to bandy this word about all over the internet, but it does not seem to have any single precise scientific/technical definition, now does it?  Use of that word should be avoided as people just say it in order to sound ultra-dramatic and im-por-tant.

[InquilineKea]

Neurotoxin: an agent that (directly or indirectly) kills neurons in a way that isn't really recoverable (downregulation is *not* neurotoxicity, since it is recoverable) - anything that causes oxidative damage could be considered neurotoxic, as an example. So amphetamine is neurotoxic since it damages the axons of dopaminergic neurons (from which it can't really recover from), and glutamate is neurotoxic since it makes more Calcium ions flow into the cell, and calcium ions can destroy the mitochondria within neurons IIRC.

Quote

I've just read today that muscarinic stimulation produce LTD (long term depression not LTP) in NMDA. And LTD seems to be a protection mechanism as stated in a 2010 study on the LTD phenomena. Looks like nicotinic receptors are more LTP for NMDA but I didn't look too much into it yet.

Oh huh, wow, that's quite interesting, I must say. There are so many agents that improve acetylcholine transmission, and they don't seem to be neurotoxic.

Edited by InquilineKea, 14 January 2011 - 07:51 AM.

[medievil]

Because it does many things, its also an antioxidant wich would protect against excitoxiticy, besides that its not a direct agonist but a modulater, shame it was so busy modulating stuff it forgot to give me notacible benefits.