271 replies to this topic

[metaprog]

There is no contradiction in IrishMD's statement. There is, however, an implicit yet clear interpretation of the second sentence you so meticulously sought out & highlighted in an attempt to find fault with IrishMD's reasoning. The aforementioned sentences prior to the second highlighted sentence clearly stipulate the prerequisite criteria for D-Serine to agonize the NMDAr at the glycine site. Would suffixing "...without the aforementioned criteria being satisfied." to the end of the 2nd highlighted/underlined sentence better edify the reasoning for you?

Note my sarcastic & liberal use of irrelevant emoticons placed throughout my writing. It seems that is your method of trying to veil or assuage the bitter & confrontational tone of your writing. I can understand you taking exception to Irish's initially aggressive/offensive tone, but dredging up this same little tiff after it was seemingly buried is extremely juvenile of you. And if you sincerely fail to understand Irish's explanation, then you indeed lack the scientific (and logical/semantic) background to speak on said topic.

Back to our regularly scheduled program...

@UnbeatableKing - Indeed I will. That's the plan.

[ScienceGuy]

There is no contradiction in IrishMD's statement. There is, however, an implicit yet clear interpretation of the second sentence you so meticulously sought out & highlighted in an attempt to find fault with IrishMD's reasoning. The aforementioned sentences prior to the second highlighted sentence clearly stipulate the prerequisite criteria for D-Serine to agonize the NMDAr at the glycine site. Would suffixing "...without the aforementioned criteria being satisfied." to the end of the 2nd highlighted/underlined sentence better edify the reasoning for you?

Note my sarcastic & liberal use of irrelevant emoticons placed throughout my writing. It seems that is your method of trying to veil or assuage the bitter & confrontational tone of your writing. I can understand you taking exception to Irish's initially aggressive/offensive tone, but dredging up this same little tiff after it was seemingly buried is extremely juvenile of you. And if you sincerely fail to understand Irish's explanation, then you indeed lack the scientific (and logical/semantic) background to speak on said topic.

Back to our regularly scheduled program...

@UnbeatableKing - Indeed I will. That's the plan.

Please do not get me wrong... If you read any and all of my other posts on this forum you will note that I am not like that at all.

Believe me when I say that my posting had no malicious intent. I am genuinely interested in any and all new possible additions to my NOOTROPIC stack and was genuinely confused by IRISH MD's apparently contradictory statements. On the one hand D-SERINE does activate the NMDA RECEPTOR, then on the other hand it does not and hence would be perfectly safe for me to take... I in fact nearly ordered a pot to try, but then I re-read his first post and became confused...

Like I said I am not as expert in BIOCHEMISTRY as he is, and so consider him the best person to explain matters such that I can see whether or not it is safe to take. Understand?

Please kindly note that I already went to the lengths of editing my prior post to formally apologise to Irish MD for completely overreacting to the LYME DISEASE matter...

So that I cannot be falsely accused of taking information out of context, here's the two paragraphs that I have a problem with in their entirety:

D-Serine is a coagonist at the NMDA receptor and is thought to bind to the glycine binding spot, albiet with higher potency. In concert with glutamate and in the absence of magnesium, D-Serine activates the NMDA receptor and promotes calcium entry. The end result is increased transcription/translation of various gene products. In the hippocampus, activating this system promotes long term potentiation (LTP) via BDNF & trkB upregulation.

Nevertheless, D-Serine doesn't predispose to excitotoxicity even in the presence of some imagininary illness (even if it were real), because of the dynamics of the compound with its receptor. D-Serine is a co-agonist, and requires numerous criteria to be met prior to agonism. In humans and higher mammals, it requires preceeding agonism of the AMPA receptor, membrane depolarization, NMDA magnesium displacement, and accompanying binding with glutmate (or DAA/NMDA). It gets more complicated from here (receptor autoregulation, increased membrane electrical potential) but I won't confuse you. Thus, even supraphysiological levels of D-Serine will not activate the receptor. In mice, glutaminergic receptor dynamics are different (and you would know that if you had any actual scientific education). Taking DAA with D-serine still does not predispose to excitotoxicity because DAA has no affinity for the AMPA receptor.

Let me put it this way, Irish MD has stated that D-SERINE exerts its NOOTROPIC effects via activation of the NMDA RECEPTOR, wherein he explains that this occurs "In concert with glutamate and in the absence of magnesium" since it is a COAGONIST.

However, Irish MD then states that D-SERINE is a COAGONIST whose activation of the NMDA RECEPTOR is so complex and involved (detail in above paragraph) that "even supraphysiological levels of D-Serine will not activate the receptor"; in which case it won't yield its NOOTROPIC effect, given this is apparently dependant on it in fact activating the receptor, no?

Please kindly note that it is great news for me if "even supraphysiological levels of D-Serine will not activate the [NMDA] receptor" because that means I can take it!

However, if its NOOTROPIC effect is dependent upon the NMDA RECEPTOR being activated, as indicated by IRISH MD's original post, then that's surely a bummer, because whilst I can take it, doing so won't yield any NOOTROPIC effect even if I take "supraphysiological levels"

You see the problem?

IRISH MD - Can you please be kind enough to answer this conundrum... if I can take this stuff safely (even given I have a pre-existing CNS LYME induced state of NMDA RECEPTOR OVERSTIMULATION) I'll be ordering a pot of it right away and will gladly feedback my personal experience with it

Edited by ScienceGuy, 29 August 2012 - 08:15 PM.

[CIMN]

requires preceeding agonism of the AMPA receptor, membrane depolarization, NMDA magnesium displacement, and accompanying binding with glutmate (or DAA/NMDA). It gets more complicated from here (receptor autoregulation, increased membrane electrical potential

perhaps the fact that it requires so many conditions to be met to act as a co agonist reduce its toxicity potential?
it acts as a co agonist but that doesn't mean it will activate the receptor. its until its further conditions are met that it acts as a agonist (what I'm assuming)

Edited by CIMN, 29 August 2012 - 07:53 PM.

[ScienceGuy]

requires preceeding agonism of the AMPA receptor, membrane depolarization, NMDA magnesium displacement, and accompanying binding with glutmate (or DAA/NMDA). It gets more complicated from here (receptor autoregulation, increased membrane electrical potential

perhaps the fact that it requires so many conditions to be met to act as a co agonist reduce its toxicity potential?
it acts as a co agonist but that doesn't mean it will activate the receptor. its until its further conditions are met that it acts as a agonist (what I'm assuming)

Mmmm... But the problem is that, according to Irish MD's original post, the desired objective of "long term potentiation (LTP) via BDNF & trkB upregulation" is only attained via actual activation of the NMDA RECEPTOR

[unbeatableking]

@Science Guy

Ever hear of 'rate limiting reactants'?

D-Serine is implicated in cell signaling and is also an NMDA receptor agonist. It is not however, the sole agonist at the said receptor.

In the absence of other metabolites that take part in the agonism of the aforementioned receptor, the NMDA receptor will fail to activate.

All of these metabolites are similarly limited, be it because of built-in physiological safeguards (BBB crossing mechanisms) or deficits brought upon by the physiological catabolism of said metabolites.

Here's a simple example:

The synthesis of ATP begins with the glycolysis cycle which leads to the formation of NADH and Pyruvate. The pyruvate undergoes decarboxylation where it is thereby converted to a two carbon acetyl group that is shuttled towards a coenzyme a molecule.

From there the acetyl-coa goes through the TCA cycle leading to the formation of NADH and FADH2. The electron pairs attached to these molecules are shuttled through the electron transport chain which creates an ionic gradient. The end point being an oxygen molecule.

All of this leads to the synthesis of ATP. They call this the oxidative phosphorylation pathway.

This isn't the only ATP-synthesizing pathway in the body. You also have the substrate level phosphorylation pathway - ergo, directly attaching a phosphate group to an ADP molecule.

This example should tell you how complicated the physiological mechanisms in the body are. This is what Irish MD was trying to say: we have many built-in biological safeguards that prevent such issues from occurring.

Remember my query regarding the rate-limiting reactant? Human beings can easily synthesize acetyl groups, as you can see, which makes it possible for us to synthesize acetylcholine via the action of acetyltransferase.

But why do you think so many people recommend the exogenous supplementation of ALCAR?

Edited by unbeatableking, 29 August 2012 - 08:18 PM.

[ScienceGuy]

@Science Guy

Ever hear of 'rate limiting reactants'?

D-Serine is implicated in cell signaling and is also an NMDA receptor agonist. It is not however, the sole agonist at the said receptor.

In the absence of other metabolites that take part in the agonism of the aforementioned receptor, the NMDA receptor will fail to activate.

All of these metabolites are similarly limited, be it because of built-in physiological safeguards (BBB crossing mechanisms) or deficits brought upon by the physiological catabolism of said metabolites.

...This is what Irish MD was trying to say: we have many built-in biological safeguards that prevent such issues from occurring...

My problem specifically lies with the fact that apparently in order to achieve the desired objective of LONG-TERM POTENTIATION using D-SERINE, activation of the NMDA RECEPTOR is required. Is that the case? Or does it in fact provide its NOOTROPIC benefits without fully activating the NMDA RECEPTOR?

I am totally up for trying this stuff out if I can do so safely

Edited by ScienceGuy, 29 August 2012 - 08:35 PM.

[unbeatableking]

D-Serine is an NMDA receptor agonist, specifically at the glycine binding site. This is it's main nootropic MOA. What is your point exactly?

Edited by unbeatableking, 29 August 2012 - 08:38 PM.

[unbeatableking]

Do you want to know the safety of the substance within a pathological context? Ergo, among those suffering from CNS abnormalities?

Isn't the right place to ask. Irish MD is a doctor but he doesn't possess the legal right or capacity to dispense advice in your case.

Besides, even if he did, the man knows nothing about your case file. We are discussing everything from a theoretical perspective.

[ScienceGuy]

D-Serine is an NMDA receptor agonist, specifically at the glycine binding site. This is it's main nootropic MOA. What is your point exactly?

So its primary NOOTROPIC mechanism of action is indeed via AGONISM of the NMDA RECEPTOR. Thank you. That was my understanding.

I think I'm going to order some of it and try it, starting with a very, very low dose; and see how I respond to it.

Because I am worried I might react badly to it, I'll do a mini placebo blind trial on myself to eliminate any possibility of the NOCEBO EFFECT.

I'll feedback how I get on.

Thanks for clarifying; and again, my humblest apologies for derailing the thread earlier

[unbeatableking]

We are here to discuss the substance and its merits amongst normal populations.

Three of us have made orders and will log it as soon as we receive the product. We are also here to discuss possible methods of increasing the efficacy of this stack.

This however, is not the place to discuss the substance within a pathological context. This will sidetrack the discussion and confuse viewers.

[ScienceGuy]

We are here to discuss the substance and its merits amongst normal populations.

Three of us have made orders and will log it as soon as we receive the product. We are also here to discuss possible methods of increasing the efficacy of this stack.

This however, is not the place to discuss the substance within a pathological context. This will sidetrack the discussion and confuse viewers.

Understood. I wasn't planning on doing a log as such; I was just going to confirm via a singular post how I got on with it. But your point is valid, so I'll be trying it purely for my own interest, and will keep my findings to myself.

I will certainly be very intrigued to read how you three get on with it. Thanks again and good luck!

Edited by ScienceGuy, 29 August 2012 - 11:05 PM.

[gbpackers]

We are here to discuss the substance and its merits amongst normal populations.

Three of us have made orders and will log it as soon as we receive the product. We are also here to discuss possible methods of increasing the efficacy of this stack.

This however, is not the place to discuss the substance within a pathological context. This will sidetrack the discussion and confuse viewers.

Understood. I wasn't planning on doing a log as such; I was just going to confirm via a singular post how I got on with it. But your point is valid, so I'll be trying it purely for my own interest, and will keep my findings to myself.

I will certainly be very intrigued to read how you three get on with it. Thanks again and good luck!

why don't you make a separate thread with a disclaimer of your condition and how you react to it? So we can have a record of how someone with your condition reactions to the compound. I personally have been on D-serine for a couple weeks I think now and I feel slight energy boost after taking it, and I guess I feel a little bit smarter lol. Not sure how else to describe it. I shall continue taking it because I have not noticed anything negative and it tastes like sugar! I take pramiracetam, creatine, beta alanine, fish oil, green tea, and oxiracetam (occasionally) as well. Drink a couple beers on the weekends as well.

Edited by gbpackers, 30 August 2012 - 03:39 AM.

[Galantamine]

Let me put it this way, Irish MD has stated that D-SERINE exerts its NOOTROPIC effects via activation of the NMDA RECEPTOR, wherein he explains that this occurs "In concert with glutamate and in the absence of magnesium" since it is a COAGONIST.

However, Irish MD then states that D-SERINE is a COAGONIST whose activation of the NMDA RECEPTOR is so complex and involved (detail in above paragraph) that "even supraphysiological levels of D-Serine will not activate the receptor"; in which case it won't yield its NOOTROPIC effect, given this is apparently dependant on it in fact activating the receptor, no?

Supraphysiological levels of D-serine will not activate the NMDA receptor in a vacuum/alone/by itself. It requires the criteria I listed previously prior to activation (co-agonism, receptor upstream activation, intracellular depoarlization).

It's NOOTROPIC (notice the capital letters? I can be an petulant child too) modality is secondary to its pharmacodynamic characteristics: higher potency. Potency means that it can produce a given effect at a lower concentration to the same degree as another compound requiring a higher concentration. Hopefully you can peice together the context from here (i.e. D-serine vs. glycine).

[ScienceGuy]

why don't you make a separate thread with a disclaimer of your condition and how you react to it? So we can have a record of how someone with your condition reactions to the compound. I personally have been on D-serine for a couple weeks I think now and I feel slight energy boost after taking it, and I guess I feel a little bit smarter lol. Not sure how else to describe it. I shall continue taking it because I have not noticed anything negative and it tastes like sugar!

Thank you for the suggestion... I might just do that!

Individuals with a pre-existing state of NMDA RECEPTOR OVERSTIMULATION are not extremely rare, since there are numerous circumstances that cause it, so I think that is a great idea

Good to hear it tastes like sugar; that'll make my mini-placebo-blind personal trial easier to administer; although I think I'll cap both the D-SERINE and the PLACEBO just to be sure

Edited by ScienceGuy, 01 September 2012 - 07:29 AM.

[X_Danny_X]

im confused a little bit. so D-Serine can activate the NMDA receptor on its own? Or it needs to be stacked with other NMDA agonists?

So if it is alone, then I just need to buy it and enjoyed its nootropic affect.

[ScienceGuy]

Supraphysiological levels of D-serine will not activate the NMDA receptor in a vacuum/alone/by itself. It requires the criteria I listed previously prior to activation (co-agonism, receptor upstream activation, intracellular depoarlization).

This I fully understand, but thank you for clarifying

It's NOOTROPIC (notice the capital letters? I can be an petulant child too) modality is secondary to its pharmacodynamic characteristics: higher potency. Potency means that it can produce a given effect at a lower concentration to the same degree as another compound requiring a higher concentration. Hopefully you can peice together the context from here (i.e. D-serine vs. glycine).

Firstly, in the spirit of keeping things positive I am going to ignore this: "It's NOOTROPIC (notice the capital letters? I can be an petulant child too)..."

Secondly, thank you kindly for your reply. However, I am still somewhat confused (which is almost certainly down to my misunderstanding something as opposed to any error on your part); hence, if you can be kind enough to help clarify matters I would very much appreciate it.

I understand that there exists a lengthy list of criteria all of which must be fulfilled in order for D-SERINE to activate the NMDA RECEPTOR.

On the one hand this is good news, because this means that not only is there little possibility of someone who suffers a pre-existing state of NMDA RECEPTOR OVERSTIMULATION (such as those with CNS LYME, MS, HUNTINGTON'S, PARKINSON'S etc..) exacerbating the situation by supplementing with D-SERINE; but also, there is little possibility of healthy individuals inducing NMDA RECEPTOR OVERSTIMULATION by doing so, which would be equally undesirable. In short, good news for everyone!

However, on the other hand, it is my understanding that in order for D-SERINE to exert its NOOTROPIC effect the activation of the respective NMDA RECEPTOR is a necessity... your colleague kindly clarified this earlier, nicely and succinctly:

D-Serine is an NMDA receptor agonist, specifically at the glycine binding site. This is it's main nootropic MOA.

And hence, because there exists a lengthy list of criteria, all of which must be fulfilled in order for D-SERINE to activate the NMDA RECEPTOR, doesn't that mean that unless all those criteria are fulfilled, and consequently said NMDA RECEPTOR is activated, D-SERINE won't in fact exert any NOOTROPIC effect?

In which case, to clarify, when taking supplemental D-SERINE specifically seeking to attain its NOOTROPIC effect, does this mean that one would need to deliberately ensure that all those criteria are fulfilled?

And if this is indeed the case, wouldn't the timing of when all the respective criteria are fulfilled be similarly vital? In that specifically it would be important to ensure that all the criteria are fulfilled specifically at the time at which the D-SERINE is absorbed fully into the bloodstream and hits peak plasma levels, as opposed to when you swallow it?

If so, then the time taken for D-SERINE to achieve PEAK PLASMA LEVEL following PER ORAL administration would be a vital piece of information... In which case, do you happen to know what it is?

RE: POTENCY - Thank you for clarifying this, but I do know what potency is; and surely potency only becomes a relevant factor if all the criteria are fulfilled for D-SERINE to activate the respective NMDA RECEPTOR and hence exert its NOOTROPIC effect? Please do not hesitate to correct me if I am wrong

Edited by ScienceGuy, 01 September 2012 - 10:23 AM.

[Galantamine]

Scienceguy, you need to distill your thoughts into more clear and concise questions. Unfortunately, I don't have all day to examine forum posts. Brevity is a virtue.

[Galantamine]

im confused a little bit. so D-Serine can activate the NMDA receptor on its own? Or it needs to be stacked with other NMDA agonists?

So if it is alone, then I just need to buy it and enjoyed its nootropic affect.

All of the ligands necessary for NMDA activation are already present with your CNS. The amounts of each ligand at that particular temporal point in space is the question, and secondary to rate limiting reactions, BBB transduction, compartmentalisation, and metabolic deactivation (among many others). The speeds & strengths of activation is what separates higher mammals from lower, and from great thinkers from lesser (mildly philosophical point). This latter is the universal underlying reasoning behind *safely* amplifying NMDA signaling - enhancing cognition. D-Serine is a more potent co-agonist at the NMDA receptor then its more abundant cousin, glycine, and so supplementing with D-Serine is a practical, and novel, way to enhance NMDA activation. Since it is *limited* by prior AMPA activation (among other criteria), it can be *safely* used for this purpose.

[X_Danny_X]

im confused a little bit. so D-Serine can activate the NMDA receptor on its own? Or it needs to be stacked with other NMDA agonists?

So if it is alone, then I just need to buy it and enjoyed its nootropic affect.

All of the ligands necessary for NMDA activation are already present with your CNS. The amounts of each ligand at that particular temporal point in space is the question, and secondary to rate limiting reactions, BBB transduction, compartmentalisation, and metabolic deactivation (among many others). The speeds & strengths of activation is what separates higher mammals from lower, and from great thinkers from lesser (mildly philosophical point). This latter is the universal underlying reasoning behind *safely* amplifying NMDA signaling - enhancing cognition. D-Serine is a more potent co-agonist at the NMDA receptor then its more abundant cousin, glycine, and so supplementing with D-Serine is a practical, and novel, way to enhance NMDA activation. Since it is *limited* by prior AMPA activation (among other criteria), it can be *safely* used for this purpose.

Awesome Doctor! So I can just safely buy this product and just take it. I am already stacking the Uridine stack along with the CILTP stack.

Should I expect a nice boost in cognitive thinking and processing immediately or will it take a few days to feel the effect?

[unbeatableking]

^

In theory the effect should be immediate. D-Serine is simply another metabolite after all. Shuttled through the CNS and what-not.

Glutamate, as Irish MD has mentioned, is readily available in your system. There are four pounds of it in your body, most of which can be found in muscle tissue and your CNS.

Do note that most of it is replenished via the consumption of protein, which yields glutamine.

[X_Danny_X]

i see, i eat alot of eggs with the yolk, pasture eggs that is. not those crappy ones you buy at the supermarket. grass fed beef sometimes, cannot buy them all the time since they are expensive as hell.

was a dose established here? i read to the thread and i didnt see it. i could of missed it.


just remember that it is good to take it with a racetam. i take noopept. though i dont know if noopept is good take orally with food since some argue that it gets breakdown by the enzymes and make most of it unusable.

the method of choice some had said is to take sublingually with milk or juice. but man noopept has a nasty bitter taste, it is like tasting alcohol 1000 times strong.

Edited by X_Danny_X, 01 September 2012 - 10:27 PM.

[unbeatableking]

1.5 to 2 grams for the D-Serine. Albeit I do believe 2 grams is much more convenient as most capsules are built to fit one gram amounts exactly.

The noopept issue is somewhat contentious. Although I don't think the sublingual method is necessary as the substance has been shown to have a good bioavailability.

Noopept (Russian: Ноопепт; GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) is a medication promoted and prescribed in Russia and neighbouring countries as a nootropic remedy. It is derived from the racetam family of drugs and shares similar mechanisms of action,[1][2] but is up to 1000 times more potent than the prototypical racetam drug, piracetam.[3] Animal studies have shown noopept to be neuroprotective and enhance memory in various different tests.[4][5][6][7] Unusually for a peptide-derived compound, noopept displays both high oral bioavailability and good blood-brain barrier penetration,[8][9] and human studies have shown promising results, with potential application in the treatment of Alzheimer's disease.[10]

Edited by unbeatableking, 01 September 2012 - 10:34 PM.

[Cognizant]

Excellent, now we are getting somewhere! So, now that we have decided that D-Serine is a "safe" way to increase NMDA activation our next focus, besides anecdotes/reviews by the members of this community as to the efficacy of any sort of NMDA activation stack, is to look at the interaction between AMPA modulating compounds (see: racetams and some others) and NMDA activators. IrishMD, since we all know that AMPA and NMDA interact in numerous ways and, most importantly in this context, that AMPA "limits" NMDA the question at hand is how will the introduction of AMPA modulating compounds affect this stack (ie. positively, as in the usage of racetams will increase AMPA activity and thus increase NMDA linearly or, more likely, the usage of racetams will increase AMPA activity which will lessen the limitations on NMDA and allow for a proportional increase in NMDA activity)?

If the latter is true then we may be looking at potential excitotoxicity down the road, but I could be completely wrong? Your (the forum's) thoughts?

[X_Danny_X]

1.5 to 2 grams for the D-Serine. Albeit I do believe 2 grams is much more convenient as most capsules are built to fit one gram amounts exactly.

The noopept issue is somewhat contentious. Although I don't think the sublingual method is necessary as the substance has been shown to have a good bioavailability.

Noopept (Russian: Ноопепт; GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) is a medication promoted and prescribed in Russia and neighbouring countries as a nootropic remedy. It is derived from the racetam family of drugs and shares similar mechanisms of action,[1][2] but is up to 1000 times more potent than the prototypical racetam drug, piracetam.[3] Animal studies have shown noopept to be neuroprotective and enhance memory in various different tests.[4][5][6][7] Unusually for a peptide-derived compound, noopept displays both high oral bioavailability and good blood-brain barrier penetration,[8][9] and human studies have shown promising results, with potential application in the treatment of Alzheimer's disease.[10]

I see, that is the thread where it was talked about and people were debating if the Russian site was correct when it came to bioavailabilty. Good damn Noopept is nasty when taking it orally.

D-Serine, a good place to buy it from is from Smart Powders. Any other good vendors with better price for the gram or Smart Powders is the best place to buy it?

[unbeatableking]

SmartPowders is currently the best place to purchase the substance from. Apart from that, Prototype Nutrition.

[timjeezy]

I would be interested in hearing about anyone's experiences with D-Serine. For example, does it go well with piracetam or other racetams?
I am considering placing an order for D-Serine at some point in the near future, but would like to hear how it is going for those who are or have been using D-Serine.

Edited by timjeezy, 07 September 2012 - 01:23 AM.

[CIMN]

so.. the idea as i heard is that D-Serine would combine well with either D-aspartic acid as well as piracetam?

I'm thinking: stack of: D-Serine + Piracetam + D-aspartic acid (but how much of each is safe?)


so its ok? to take piracetam, d-serine, aspartic acid, together? (in theory they should all potentiate each other if i am getting that correct) no danger of toxicity..?

Irish MD, on 06 July 2012 - 10:59 AM, said:


Irish MD, on 27 August 2012 - 08:50 AM, said:

Nevertheless, D-Serine doesn't predispose to excitotoxicity even in the presence of some imagininary illness (even if it were real), because of the dynamics of the compound with its receptor. D-Serine is a co-agonist, and requires numerous criteria to be met prior to agonism. In humans and higher mammals, it requires preceeding agonism of the AMPA receptor, membrane depolarization, NMDA magnesium displacement, and accompanying binding with glutmate (or DAA/NMDA). It gets more complicated from here (receptor autoregulation, increased membrane electrical potential) but I won't confuse you. Thus, even supraphysiological levels of D-Serine will not activate the receptor. In mice, glutaminergic receptor dynamics are different (and you would know that if you had any actual scientific education). Taking DAA with D-serine still does not predispose to excitotoxicity because DAA has no affinity for the AMPA receptor.

D-Serine is a coagonist at the NMDA receptor and is thought to bind to the glycine binding spot, albiet with higher potency. In concert with glutamate and in the absence of magnesium, D-Serine activates the NMDA receptor and promotes calcium entry. The end result is increased transcription/translation of various gene products. In the hippocampus, activating this system promotes long term potentiation (LTP) via BDNF & trkB upregulation.

The racetams allosterically activate this system and would synergize well with D-Serine. Specifically, Aniracetam (or the ampakines) would promote magnesium displacement via AMPA activation & cellular depolarization, and Piracetam would synergize more locally on the NMDA receptor itself.

Edited by CIMN, 07 September 2012 - 05:11 AM.

[unbeatableking]

^

D-Aspartic Acid is a testosterone booster. It raises overall testosterone levels. It is not feasible for long-term use however.

It isn't neurotoxic. I'd be much more worried about the effects the stack might have on your nephrotic and endocrinological systems, and even then, as long as one doses it properly, I still see no harm.

I would be interested in hearing about anyone's experiences with D-Serine. For example, does it go well with piracetam or other racetams?
I am considering placing an order for D-Serine at some point in the near future, but would like to hear how it is going for those who are or have been using D-Serine.

I have yet to hear of any negatives associated with the supplement. Most reports speak of an increase in energy and mood however, cannot comment on memory.

[CIMN]

^

D-Aspartic Acid is a testosterone booster. It raises overall testosterone levels. It is not feasible for long-term use however.

It isn't neurotoxic. I'd be much more worried about the effects the stack might have on your nephrotic and endocrinological systems, and even then, as long as one doses it properly, I still see no harm.

ok, well for short term use it seems then, ill stick with d serene and piracetam and occasionally try the aspartic acid.

[unbeatableking]

For those of you who are on D-Serine or have plans of taking it, we have established that the substance is indeed safe from a cognitive perspective.

There is a caveat however: the substance is somewhat nephrotoxic, in a dose-dependent fashion.

Which is why it is recommended that people stay within 3 to 5 grams every day. Avoid going beyond that.