271 replies to this topic

[timjeezy]

^

Unbeatableking cares for his fellow man. <3 Just a word of advice. <3

Both have similar MOA's, so I don't see any reason why we can't discuss the two together.

Thanks for the advice. Sarcosine it is then (found 100 grams for $10 so why not).
Luckily I have not ordered any D-Serine yet. I may still try D-Serine at some point if I could order a smaller amount just to have a taste.

I apologize ahead of time if I missed this, but how much Sarcosine would you recommend taking for one dose? 1.0 gram or so?

Edited by timjeezy, 10 September 2012 - 08:56 PM.

[unbeatableking]

One gram twice a day, as indicated by a study.

[gbpackers]

I think I read one of the posts saying D-serine kills your verbal ability.

No Idea how you guys notice such effects from it. I pretty much notice a slight energy boost and feel smarter after taking it. I take 1.5g twice a day.. and have been doing well with my test prep..

[unbeatableking]

^

I took it stand-alone after a meal and a nap.

You are on a lot of different things.

[CIMN]

3. I recommend starting with Sarcosine. If you like it then you can try D-serine.

ok, perhaps i will try one and the other and compare the two..
it was a bit confusing to me, since this thread is mainly about d-serine, so i presumed that we should stick with that?

Just want to Ask or mention.. if Sarcosine is better then D-serine then why doesn't Irish MD mention that? i wonder which he would recommend as he brought up this d-serine info.

[gbpackers]

^

I took it stand-alone after a meal and a nap.

You are on a lot of different things.

lol true i'm on a shitload of things

[unbeatableking]

3. I recommend starting with Sarcosine. If you like it then you can try D-serine.

ok, perhaps i will try one and the other and compare the two..
it was a bit confusing to me, since this thread is mainly about d-serine, so i presumed that we should stick with that?

Just want to Ask or mention.. if Sarcosine is better then D-serine then why doesn't Irish MD mention that? i wonder which he would recommend as he brought up this d-serine info.

Because Irish MD is a man of science.

There aren't a lot of studies/journals/articles/anecdotes to confirm the efficacy of Sarcosine as a stand-alone cognitive supplement amongst normal populations. Most of the aforementioned were done on schizophrenic patients.

Plus in theory, D-serine should indeed be more efficacious than Sarcosine given it's MOA.

You can't necessarily base real-world results on microbiological processes however, which explains the varied number of responses to different nootropics on here.

I have talked to him, he says he has tried and used Sarcosine with great effect. He has not tried D-serine yet however.

[Galantamine]

3. I recommend starting with Sarcosine. If you like it then you can try D-serine.

ok, perhaps i will try one and the other and compare the two..
it was a bit confusing to me, since this thread is mainly about d-serine, so i presumed that we should stick with that?

Just want to Ask or mention.. if Sarcosine is better then D-serine then why doesn't Irish MD mention that? i wonder which he would recommend as he brought up this d-serine info.

Because Irish MD is a man of science.

There aren't a lot of studies/journals/articles/anecdotes to confirm the efficacy of Sarcosine as a stand-alone cognitive supplement amongst normal populations. Most of the aforementioned were done on schizophrenic patients.

Plus in theory, D-serine should indeed be more efficacious than Sarcosine given it's MOA.

You can't necessarily base real-world results on microbiological processes however, which explains the varied number of responses to different nootropics on here.

I have talked to him, he says he has tried and used Sarcosine with great effect. He has not tried D-serine yet however.

Well said.

[CIMN]

Irish MD, thanks for this thread and your knowledge as well,

I've been wondering, would taking these nmda agonist cause the receptors to get desensitized? Im not a expert on the topic but in regards to the ion influx from these nmda agonist, i expect it would caus a generation of a membrane potential... would these nmda agonist help or harm that process? is it a sustainable effect? or would they eventually cause a desensitization of the receptor?

Edited by CIMN, 11 September 2012 - 06:19 PM.

[unbeatableking]

The NMDA agonism process is designed to elicit the influx of Ca 2+ ions leading to the momentary depolarization of the axon, thereby establishing a membrane potential.

It should help that process.

[unbeatableking]

Umm, with regards to desensitization. Do you mean tachyphylaxis/downregulation/tolerance?

There is a slight possibility for this. If you are worried about this conundrum, then it should be fine to consume a beer once or twice a week in order to antagonize your receptors. Doing so leads to a receptor rebound of sorts leading to a rise in NMDA activity.

You can also take the occasional break off of these substances. Perhaps take them four times a week at most? Your CNS has a natural receptor upregulating mechanism. Besides, I don't find it wise to take these substances everyday, not in the long-term at least.

[CIMN]

The NMDA agonism process is designed to elicit the influx of Ca 2+ ions leading to the momentary depolarization of the axon, thereby establishing a membrane potential.

It should help that process.

yes, but what i meant was, do they eventually lose effect? (is it a good idea to continually have the nmda receptor agonized?) i expect overtime the ability to generate a membrane potential gets reduced because of desensitization.

Edited by CIMN, 11 September 2012 - 06:51 PM.

[unbeatableking]

^

Refer to my post above.

[CIMN]

^

Refer to my post above.

not tolerance in terms of receptor changes but i mean desensitization occurring from the ion influx. (sorry I'm no expert haha) ok so the d serene will "lead to the momentary depolarization of the axon, thereby establishing a membrane potential."

but what i mean is, does the continual depolarization (from d serene use) eventually get reduced over time?

in a sense, tolerance to the ion influx?

Edited by CIMN, 11 September 2012 - 08:04 PM.

[unbeatableking]

Within the context of NMDA agonism you say? The ion influx is a physiological by-product of the agonism of NMDA-receptors. The axons have no say in this.

If the receptors call for the entry of Ca 2+, then the axons will respond accordingly.

And axons don't really work that way. There is an 'all-or-nothing' principle in place. Once the axon crosses over the voltage threshold then the action potential/EPSP will occur to the same extent that it always does.

Which is why neurotoxicity is an issue. The influx of Ca 2+ can occur to the point of neural apoptosis via the generation of NOS/ROS because of the continued agonism of NMDA-receptors.

[CIMN]

If the receptors call for the entry of Ca 2+, then the axons will respond accordingly.

And axons don't really work that way. There is an 'all-or-nothing' principle in place. Once the axon crosses over the voltage threshold then the action potential/EPSP will occur to the same extent that it always does.

Which is why neurotoxicity is an issue. The influx of Ca 2+ can occur to the point of neural apoptosis via the generation of NOS/ROS because of the continued agonism of NMDA-receptors.

ah ok thanks for elaborating on that, so the point is that, we want the minimum Ca 2+ neccesary to achieve an action potential?

[unbeatableking]

If the receptors call for the entry of Ca 2+, then the axons will respond accordingly.

And axons don't really work that way. There is an 'all-or-nothing' principle in place. Once the axon crosses over the voltage threshold then the action potential/EPSP will occur to the same extent that it always does.

Which is why neurotoxicity is an issue. The influx of Ca 2+ can occur to the point of neural apoptosis via the generation of NOS/ROS because of the continued agonism of NMDA-receptors.

ah ok thanks for elaborating on that, so the point is that, we want the minimum Ca 2+ neccesary to achieve an action potential?

There really isn't a 'minimum' to be spoken of. Not within the context of ionic gradients.

Simply put, we want to turn the inside of the axon positive. That is it.

[unbeatableking]

I have been experimenting with both D-Serine and Sarcosine during the past few days.

I've promised Irish MD that I would conduct a comprehensive log with regards to both products. I will do so, but I waited till I was able to gauge the purported efficacies of both products.

So far, Sarcosine is the clear winner. It is a stimulant. Allows me to think faster and to some extent, it helps keep me awake. I have not experienced this with D-serine. The general consesus is that neural processing speed and working memory are heavily interrelated, given this reality, you can speculate on the effect sarcosine may have on your memory.

Synergises very well with Piracetam. Clinical dosages range between one to five grams a day.

The best dose, from a dose to dose (one-time dosage) basis in my opinion, is two grams. It is simply more cost-effective that way. Half-life is somewhere around five to six hours.

Apart from that, Sarcosine is cheap. Incredibly so.

[unbeatableking]

This is odd.

I can think, encode and process information at a faster rate than usual. My memory is significantly better as well.

But the process is physiologically taxing.

[Psionic]

how physiologically taxing, do you mean its somewhat stressful?

[unbeatableking]

Let me use an analogy:

My mind is a stomach. It can now devour huge amounts of information, but in the process of my binge eating, I have developed a mental stomach ache.

Some things that might aid in this conundrum:

1. Eating.

2. A short break.

2. Consumption of a choline source.

I feel much better now.

Either way, Sarcosine is going to be a mainstay in my stack.

[CIMN]

If the receptors call for the entry of Ca 2+, then the axons will respond accordingly.

And axons don't really work that way. There is an 'all-or-nothing' principle in place. Once the axon crosses over the voltage threshold then the action potential/EPSP will occur to the same extent that it always does.

Which is why neurotoxicity is an issue. The influx of Ca 2+ can occur to the point of neural apoptosis via the generation of NOS/ROS because of the continued agonism of NMDA-receptors.

ah ok thanks for elaborating on that, so the point is that, we want the minimum Ca 2+ neccesary to achieve an action potential?

There really isn't a 'minimum' to be spoken of. Not within the context of ionic gradients.

Simply put, we want to turn the inside of the axon positive. That is it.

I've been wondering about piracetam it being a allosteric regulator,
essentially what is the difference between piracetams MOA vs sarcosine, they essentially do the same thing? piracetam modulates the ions channels, but it works on Ca 2+ like an agonist?

im picturing the receptor as a lock, and the key is the agonist or allosteric regulator, and the more you add agonist the faster ions can enter to create a action potential, am i getting that right?

Edited by CIMN, 12 September 2012 - 06:14 PM.

[unbeatableking]

An allosteric modulator changes the function of a protein by attaching to a binding site. Essentially changing the function of the ion channel.

Piracetam enhances glutaminergic transmission by allosterically modulating NMDA channels. To what extent, I am unaware of.

Sarcosine is an NMDA-receptor co-agonist in conjunction with glutamate. It is an agonist at ligand-gated binding sites. Upon the attachment of both ligands, glutamate and sarcosine, the receptor opens and calcium ions move inside.

Piracetam = altering the function of the receptor.

Sarcosine = agonizing the receptor.

Edited by unbeatableking, 12 September 2012 - 07:06 PM.

[CIMN]

An allosteric modulator changes the function of a protein by attaching to a binding site. Essentially changing the function of the ion channel.

Piracetam enhances glutaminergic transmission by allosterically modulating NMDA channels. To what extent, I am unaware of.

Piracetam = altering the function of the receptor.

Sarcosine = agonizing the receptor.

Isn't a allosteric modulator-regulator like another agonist? Irish MD says D-Serine activates the NMDA receptor and promotes calcium entry,The racetams allosterically activate this system.

in the end they achieve the same goal with different mechanisms?

Allosteric modulation of a receptor results from the binding of allosteric modulators at a different site (a "regulatory site") from that of the endogenous ligand (an "active site") and enhances or inhibits the effects of the endogenous ligand. Under normal circumstances, it acts by causing a conformational change in a receptor molecule, which results in a change in the binding affinity of the ligand. In this way, an allosteric ligand modulates the receptor's activation by its primary (orthosteric) ligand, and can be thought to act like a dimmer switch in an electrical circuit, adjusting the intensity of the response.

http://en.wikipedia....eric_modulation

Edited by CIMN, 12 September 2012 - 07:45 PM.

[unbeatableking]

An allosteric modulator is not an agonist. It does bind to a receptor site however.

It causes conformational changes, most commonly amongst proteins.

From there it can lead to a varied number of results. Some allosteric modulators ease the process by which neurotransmission occurs for example.

Sarcosine is an agonist at the glycine binding site. This binding is necessary for the entrance of calcium ions to occur.

You don't need to allosterically modulate NMDA-receptors however in order to bring about the depolarized state.

If you take Piracetam in a glutamate-depleted state for example, Piracetam will do nothing for you. Think of it as a physiological process enhancer. It is not an agonist, it aids in the agonism of receptors however, by acting on binding sites.

Edited by unbeatableking, 12 September 2012 - 08:04 PM.

[CIMN]

ok, so the allosteric regulator changes the receptor. But doesn't act as a agonist. got it.

[unbeatableking]

Hmm. Apparently, Sarcosine's half-life, on average, is at 1.6 hours.

Which leaves me to believe that the best dosing scheme would be 2 grams every two or three hours.

http://www.jci.org/a...06729/files/pdf

I hope Irish MD can share his opinion regarding this.

Edited by unbeatableking, 12 September 2012 - 08:23 PM.

[unbeatableking]

This is odd.

I have been up for 24 hours now. I have gone through both Marcel and Marias, and although my performance has indeed dropped to some extent, I am still going.

This is amazing. Hopefully I can keep this up.

[unbeatableking]

Found a study which seems to argue that D-serine and/or Glycine are competitive agonists with regards to another compound at the glycine binding site.

What other compound you ask? Believe it or not: Piracetam.

A potentiation of response to glutamate and aspartate through the glycine site of the NMDA receptor by piracetam has been reported in a Russian study. Another study showed that piracetam and aniracetam at 100 PM do not affect MK-801 binding in the presence of NMDA and glycine. If piracetam acts on the glycine regulatory site of the NMDA receptor the presence of glycine could obscure the potentiating effect of piracetam.

In theory this doesn't make any sense. Glycine and/or D-serine are necessary co-agonists at the NMDA receptor site.

[health_nutty]

My initial reaction to D-Serine is not good. Maybe the lack of sleep is getting to me so take it with a grain of salt.

D-serine is making me sleepy! Yesterday late afternoon I tried 1.5 grams on an empty stomach and felt a little light headed the rest of the day.

This morning I dropped down to 1g and I feel drained. I went for my normal 5 mile run and it felt terrible. No positive effects noticed.

I think I'm going to give this a break for a few days and try again.