Agmatine

Synapsin

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I know people requested this before, sorry for being so behind. Can't find my reference list but it should be pretty easy to find stuff if you're interested (or just post/ PM me).

Agmatine

Agmatine background

Agmatine is an amine, an organic cation, and serves as an endogenous ligand at alpha 2-adrenergic and imidazoline receptors, to which it binds with high affinity. In addition, Agmatine has properties of an endogenous neurotransmitter.

Agmatine is:

(a) Locally synthesized in brain by a specific enzyme, arginine decarboxylase;

(b) Stored in a large number of neurons with selective distribution in the CNS;

(c) Associated with small vesicles in axon terminals that, at least in hippocampus, make synaptic asymmetric (excitatory) synapses on pyramidal cells;

(d) Released from synaptosomes in a Ca(2+)-dependent manner;

(e) Enzymatically degraded by agmatinase in synaptosomes

(f) Able to block the ligand-gated NMDA receptor channel at sites distinct from ligand-binding and polyamine sites.

(g) Able to competitively inhibits the activity of all isoforms of nitric oxide synthase (with exception to eNOS which we will mention later for its effects on NO production). Agmatine meets most criteria to establish it as a novel neuromodulator in the CNS (Reis, 1999).

(h) Able to activate imidazoline receptors (high affinity as an agonist; note these are downstream effects), which raises levels of beta-endorphins (leading to an increase in glucose uptake in skeletal muscle); it also lowers blood glucose levels, giving it glucose disposal agent (GDA) like properties.

Each of these points has a specific role of important in this discussion of Agmatine, indicating its vital role in the human body.

Agmatine as a neuroprotective neuromodulator

Agmatine is said to serve as an endogenous neuroprotective neuromodulator which is co-released during neurotransmitter release. It has been reported to be an endogenous neuromodulator of mental stress and has possible beneficial effects when it comes to depression, generalized anxiety, post-traumatic stress disorder, and social anxiety. Taksande et al (2009) found that that modulation of imidazoline receptors by Agmatine are implicated in the antidepressant like effect of SSRIs and may be projected as a potential therapeutic target for the treatment of depressive disorders.

Agmatine has also been indicated to be effective when it comes to pain management and palliative care.Agmatine was shown in preclinical studies to be a safe and efficacious treatment for alleviating pain and improving quality of life in lumbar disc-associated radiculopathy.

Agmatine is a specific competitive antagonist of the NMDA receptor and its guanidine moiety makes it different than traditional NMDA receptor antagonists. It’s been used many times for treating drug addictions, and another important thing to note is that Agmatine was found as an effective preventative method when it comes to glutamatergic NMDA apoptosis.

Li et al (2003) found that Agmatine reverses the NMDA-induced intracellular Ca(2+) overloading and the decrease of monoamines (including norepinephrine, epinephrine or dopamine) contents in PC12 cells, indicating that agmatine's antidepressant-like action may be related to its modulation of NMDA receptor activity and/or reversal of the decrease of monoamine contents and Ca(2+) overloading induced by NMDA. This is an important thing to keep in mind later for when we discuss the combined usage of Agmatine and D-aspartic acid (DAA) since there would appear to be a contradiction in the usage of an NMDA antagonist and an NMDA agonist (although there truly isn’t).

In hippocampal neurons Agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore, supporting the concept that it may serve as a neuromodulator in the brain. There is evidence that agmatine is a neuroprotective molecule and reduces excitotoxic cell death induced by glutamate or NMDA. It is possible that Agmatine, co-released with glutamate, may act to inhibit the activation of NMDA receptors during conditions leading to higher glutamate release.

Relating to bulletin points (b), (c), (d) and (f), axons that innervate pyramidal cells are glutamatergic and pyramidal cells express NMDA receptors of the glutamate subclass. It has been reported that it because of this, that agmatine may be co=stored and released with glutamate as a counter regulatory molecule as seen by electrophysiological studies of hippocampal neurons by Yang (1999).

The implication of Agmatine being co-released with glutamate release gives a clear indication for its usage when it comes to disease. It’s possible that Agmatine plays a regulatory role in normal glutamatergic neurotransmission, preventing excessive activation of NMDA receptors. The importance of this is that Agmatine is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks et al., 2000) and neuropathic pain (Fairbanks et al., 1998), conditions that arise from higher NMDA receptor activation and are reversed by NMDA receptor antagonists.

Agmatine’s effects on NO production

In the human body, there are three primary Nitric Oxide synthase pathways to be concerned with, nNOS, iNos, and eNOs. Agmatine is an inhibitor of both nNos and iNos, but importantly, it is not an inhibitor of eNos. eNos generates NO in blood vessels and is involved with regulating vascular function. eNos is associated with plasma membranes surrounding cells and the membranes of Golgi bodies within cells and is calcium current dependent. Agmatine also increases Nitric Oxide (N.O) through two pathways by stimulating the release of Nitric Oxide, while also inhibiting types of Nitric Oxide Synthase (enzymes that break down N.O.). With all of this in mind, this ultimately leads to increased NOS production, leading to an overall greater pump because Agmatine is fast acting. It’s also thought that it may be a vasodilator due to its activation of imidazoline receptors (along with its effects on eNOS).

Agmatine and D-Aspartic acid (DAA)

The important thing to distinguish here is that exogenous application of Agmatine and D-Aspartic acid work on different mechanisms for the NMDA receptor, so regardless of one being an antagonist and the other an agonist, they do not overlap. Exogenous D-aspartic acid application utilizes the R-type VGCCs and none of the others, while exogenous Agmatine is said to use the L-type VGCCs and shows no signs of inhibition of the R-type VGCCs.

Other Agmatine benefits

Agmatine can also work through stimulating the release of pituitary hormones, including Luteinizing Hormone (LH) and Growth Hormone (GH). It also increases levels of peptide Y via alpha-2-adrenoceptors within the PVN. Agmatine has a variety of benefits, and can be beneficial and desirable for athletes and bodybuilders as well as fitness enthusiasts and people in search of a healthier lifestyle as they age.

A summary of Agmatine, why you should use it and how should you use it

Agmatine is an effect supplement when it comes to pain management, neuropathic pain, ischemic injury prevention, spinal cord injury, neurotoxicity prevention, and useful for NO production, helping give you those pumps you’ve always wanted in the gym. Agmatine is also a great supplement to pair up with d-aspartic acid to help you not only feel healthier, but actually be healthier. Agmatine works through stimulating the release of pituitary hormones, including Luteinizing Hormone (LH) and Growth Hormone (GH).

Agmatine has a variety of benefits, and can be beneficial and desirable for athletes and bodybuilders as well as fitness enthusiasts and people in search of a healthier lifestyle as they age. Agmatine also increases Nitric Oxide (N.O) through two pathways – by stimulating the release of Nitric Oxide, while also inhibiting types of Nitric Oxide Synthase (enzymes that break down N.O.), and imidazoline receptor activation (blood glucose reduction + enhanced glucose intake selective to skeletal muscles). Agmatine can also be used for improved recovery, improved endurance, improved performance, improved body composition, promoting a healthy & positive mood (anti-anxiety & antidepressant properties), increased nutrient delivery to muscle cells, an enhanced insulin response, as a neuroprotective support for good health, for improved cardiovascular health, and finally, as an antioxidant.
 
jgntyce

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Yes sir! Serious Nutrition Solutions has Agmatine XT that is very affordable!
 

Rebel1978

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Big fan myself. I buy it in bulk powder and mix it in my water and drink throughout the day. Taste is pretty rough, mix it with BCAA or Alphamine.
 
cheftepesh1

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Always in for knowldge
 
Afi140

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Good read. Gracias
 
TheMrMuscle

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And its getting banned in Europe. I work at a supplement store in Sweden and we have already seen some re-formulations come in and there are more to come.
 
TheMrMuscle

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So im still trying to find out why but the only thing ive dug up so far is this quote:

"According to the EU's novel food catalogue, a member state was asked about the status of this product and it was concluded there was no evidence of its consumption as food or ingredient before 15 May 1997 meaning it would have novel food approval before being sold in the EU."

And i dont really know what that means.
 
drejb

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So im still trying to find out why but the only thing ive dug up so far is this quote:

"According to the EU's novel food catalogue, a member state was asked about the status of this product and it was concluded there was no evidence of its consumption as food or ingredient before 15 May 1997 meaning it would have novel food approval before being sold in the EU."

And i dont really know what that means.
Sounds like they're just trying to deprive the European population from them gainzzzz
 
LeanEngineer

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Thanks for sharing. I've used agmatine for a long time now. Great ingredient.
 
LiveToLift

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Glad to see this post. Always enjoy your info posted.
 

619sss

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What's the dose for pump and LH stimulating?
Once dose? Or multiple dose?

30mins before workout?
 

hsk

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https://en.wikipedia.org/wiki/Agmatine

Since we are discussing Agmatine, the above page from wiki states that one of the MOA's of Agmatine is "direct blockade of AGEs formation". However, this wiki page is the only place I have seen Agmatine mentioned as an AGEs inhibitor/blocker. Does anyone know of any studies that can back this up? If so, what dosages would be needed for this effect and how does Agmatine compare to other AGE's inhibitors such as Aminoguanidine, Carnosine, and/or Benfotiamine?
 
money0351

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Great post!
agmatine is a staple for me because of its GDA and nitric oxide benefits
During my undergrad research, I helped conduct a study where we would measure biomarkers, substrate usage, and subjective responses of SCI patients in response to HIIT, LISS, and SS on an arm erg.
I did quite a bit of reading on SCI and came across agmatine as having a possible therapeutic application for SCI which I though was pretty interesting.
Anyways... informative posts, such as this one, are always appreciated!
 

619sss

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https://en.wikipedia.org/wiki/Agmatine

Since we are discussing Agmatine, the above page from wiki states that one of the MOA's of Agmatine is "direct blockade of AGEs formation". However, this wiki page is the only place I have seen Agmatine mentioned as an AGEs inhibitor/blocker. Does anyone know of any studies that can back this up? If so, what dosages would be needed for this effect and how does Agmatine compare to other AGE's inhibitors such as Aminoguanidine, Carnosine, and/or Benfotiamine?
Does it means it affect Carnosine the lactic acid buffer? Is that bad?
 
rtmilburn

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Great post!
agmatine is a staple for me because of its GDA and nitric oxide benefits
During my undergrad research, I helped conduct a study where we would measure biomarkers, substrate usage, and subjective responses of SCI patients in response to HIIT, LISS, and SS on an arm erg.
I did quite a bit of reading on SCI and came across agmatine as having a possible therapeutic application for SCI which I though was pretty interesting.
Anyways... informative posts, such as this one, are always appreciated!
What's SCI?
 
Synapsin

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Hey friends, a bit busy tonight, but I'll get to everyone's posts tomorrow :) cheers
 
Young Gotti

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agmatine for me is hit or miss in terms of pumps, at this point unless it's in a preworkout, I don't really use it as a pre workout and use it in my pre bed concoction

and it could just be in my head but I feel like all agmatine isn't built the same, seems like some companies are much better quality than others
 

hsk

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How much do you dose for real pumps?
Most people use 1g-1.5 grams for a pump or as a GDA. Personally, I take 1.5g preworkout. Another 1-1.5 gram later in the day. Although it provides a nice pump, I use it more for pain management. For pumps, I would probably go with 5-6g l-citrulline or nitrates. Best combo would all 3 combined.
 
LiveToLift

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Many people don't even realize it is used as a gda. They just feel it's sole purpose is them serious pumps. Lol
 
Synapsin

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What's the dose for pump and LH stimulating?
Once dose? Or multiple dose?

30mins before workout?
Not really well studied enough to come up with a dse for LH, but pump, 1-1.5g is a good dose. 30 mins preworkout is good.

https://en.wikipedia.org/wiki/Agmatine

Since we are discussing Agmatine, the above page from wiki states that one of the MOA's of Agmatine is "direct blockade of AGEs formation". However, this wiki page is the only place I have seen Agmatine mentioned as an AGEs inhibitor/blocker. Does anyone know of any studies that can back this up? If so, what dosages would be needed for this effect and how does Agmatine compare to other AGE's inhibitors such as Aminoguanidine, Carnosine, and/or Benfotiamine?
I don't see any studies or references to this, but it would not surprise me given it's effect on nitric oxide. It would not compare to the others unless I see some sort of study to read the exact effects.

How much do you dose for real pumps?
1-1.5 grams

Many people don't even realize it is used as a gda. They just feel it's sole purpose is them serious pumps. Lol
Exactly, and that its selective to skeletal muscle
 
LiveToLift

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Not really well studied enough to come up with a dse for LH, but pump, 1-1.5g is a good dose. 30 mins preworkout is good.



I don't see any studies or references to this, but it would not surprise me given it's effect on nitric oxide. It would not compare to the others unless I see some sort of study to read the exact effects.



1-1.5 grams



Exactly, and that its selective to skeletal muscle
Which is extremely beneficial. Glad you posted this information to inform everyone just how great the product truly is. It has been pretty much a staple for me since it's initial hype.
 

hsk

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I agree. This has been a staple of mine for the 3+ years.
 
warbird01

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ArA+agmatine pumps are insane. Close to on cycle pumps for me.
 
LiveToLift

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ArA+agmatine pumps are insane. Close to on cycle pumps for me.
Seems to be the result for all who have experienced the combo.
 
LeanEngineer

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ArA+agmatine pumps are insane. Close to on cycle pumps for me.
I'm actually running x gels and agmatine xt right now! so agreed:)
 
LiveToLift

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PeteRyde

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Also been a staple of mine too. Morning and night. Feel it aids in pain management and blood pressure control.
Agree it's no taste sensation though.
 
Synapsin

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Explain more about the pumps.... Vein pumps? Muscle pumps? Extra strength, endurance?
I find agmatine makes me extremely vascular, but I wouldn't say it gives you extra strength or any significant endurance.
 
rtmilburn

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I find agmatine makes me extremely vascular, but I wouldn't say it gives you extra strength or any significant endurance.
What supplements would you say are the best for strength? Both acute and for more long term/permanent strength gains.
 
Synapsin

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What supplements would you say are the best for strength? Both acute and for more long term/permanent strength gains.
Tbh, nothing will be that effective short term. Long term, I recommend creatine, betaine, KSM 66, shilajit, and some other stuff (I am very partial to nitrates and citrulline as well, although that is anecdotal). I don't like to supplement too much; ergonine + HV covers me for all of these minus the KSM (which is in Erase pro + anyways) and the shilajit (which is in TruZMA). I like to design things I would actually use.
 

InItForGainz

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What supplements would you say are the best for strength? Both acute and for more long term/permanent strength gains.
Acute
Citrulline, Caffeine, Agmatine, Nitrates.
Long Term
Creatine, Beta-Alanine, PA, Choline.
 
rtmilburn

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Tbh, nothing will be that effective short term. Long term, I recommend creatine, betaine, KSM 66, shilajit, and some other stuff (I am very partial to nitrates and citrulline as well, although that is anecdotal). I don't like to supplement too much; ergonine + HV covers me for all of these minus the KSM (which is in Erase pro + anyways) and the shilajit (which is in TruZMA). I like to design things I would actually use.
Thoughts on amentoflavone?
 
Synapsin

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One last question, are you gonna continue to do write ups likes this? Because I love them and love learning from you!
Of course, I love doing write ups and helping out. If you have any particularly topics in mind, let me know :)
 
rtmilburn

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Could we get a write up on peakO2, elevateATP, peakATP, hica, creatinol-o-phosphate, and Ecklonia Cava. In that order would be my preference :)
 
Synapsin

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Could we get a write up on peakO2, elevateATP, peakATP, hica, creatinol-o-phosphate, and Ecklonia Cava. In that order would be my preference :)
Hmm. Maybe one of the ATP's or HICA is good. COP is too old and doesn't have anything worthwhile out in the last 20 years, thanks for the suggestions
 
Ape McGrapes

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Hmm. Maybe one of the ATP's or HICA is good. COP is too old and doesn't have anything worthwhile out in the last 20 years, thanks for the suggestions
So your suggesting that C-O-P is bunk or just lacks the science?

I've used it preworkout, but can't say if it helped or not.
 
Synapsin

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So your suggesting that C-O-P is bunk or just lacks the science?

I've used it preworkout, but can't say if it helped or not.
To be honest, lacks the science. I had good anecdotal experience with it (very minor though), but it always made it really have to use the bathroom so it was annoying and I cut it out. I was actually one of the reasons SNS started making it. I don't think it's justifiable based on very extrapolated data without further research at this time.
 

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