Fermentation produced agmatine sulfate. contact mark at:gx8@genabolix.com

1. AGMAPURE
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by GENABOLIX
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AGMAPURE®
Trademark: AGMAPURE®
Product
Name:
Agmatine Sulfate
CAS NO: 2482-00-0
Other
Names:
C5 H14 N4 •H2 O4 S
Guanidine, N-(4-aminobutyl)-, sulfate (1:1)
Guanidine, (4-aminobutyl)-, sulfate (1:1)
(8CI,9CI);
MF:
C5H16N4O4
Molecular
Weight:
228.27g/mol
Solubility in
Water:
50g/L (25 °C)
Density: 1.328±0.06 g/cm3
MP: 234-238°C
I. Introduction of AGMAPURE®
Recently Agmatine has gained wide interest as a breakdown metabolite
of Arginine with a multitude of physiological functions. Agmatine Sulfate,
the commonly used stable salt of Agmatine, is a promising supplement
rapidly drawing the attention of the athletic performance market.
Agmatine Sulfate is thought to improve nutrient partitioning thus leading
to more glycogen storage and increased water retention within the
muscle. It also increases the level of nitric oxide (NO), which can increase
the "PUMP" that athletes look for when weight training. Although Arginine
also has this function, the cost of it is quite expensive and, if you want
obvious effects, you need at least 6 times more dose than Agmatine, no
matter in what form of salt or ester it is.
Attracted by such an application prospect, we’ve developed the new
generation product of Agmatine Sulfate: AGMAPURE®
.
Currently, AGMAPURE®
is the unique Green Agmatine Sulfate in sports
nutrition market. It’s in high purity, produced by natural biological process
and away from the neurohazard impurity Arcaine, which exists in almost
all the other brands of Agmatine Sulfate.

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II. AGMAPURE®
VS. Putrescine-related Agmatine Sulfate
Why Genabolix® introduced
AGMAPURE®
into the
currently crowded market of
Agmatine Sulfate?
Because till now, almost all the competitor products of Agmatine Sulfate use
the same synthesis process, starting from notorious putrescine!
Production Process of
Putrescine-related
Agmatine Sulfate Putrescine is a foul-smelling organic compound related to cadaverine. Both of putrescine and
cadaverine are produced by the breakdown of amino acids in living and dead organisms, and
both are toxic in large doses. The two compounds are not only responsible for the foul odor of
putrefying flesh, but also contribute to the odor of such processes as bad breath and bacterial
vaginosis.
The putrescine will finally become hardly removable impurity in final Agmatine Sulfate. It may
be in the form of putrescine monosulfate, or even base form, which will be quite unidentified
impurity in final Agmatine Sulphate and can’t be purified with current technology, because its
chemical structure is highly similar to that of Agmatine. Although some companies can turn out
a max purity of 98%, there is still detectable impurity, Arcaine, which is harmful to human brain
and will increase the risk of amnesia.
We adopt natural compound as raw material, and turn it into AGMAPURE®
by
completely natural biological process. Therefore, AGMAPURE®
is clean and safe,
without introducing in any unwanted and unknown impurity. It has been
demonstrated by our purity test.
Production Process of
AGMAPURE®

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III. Purity Test of AGMAPURE®
& Putrescine-related Agmatine Sulfate
Purpose and Scope
The purity test describes the research of impurity profile of AGMAPURE®
and the Putrescine-related Agmatine
Sulfate to show the difference between them.
Method Description
Method: HPLC-UV(for purity determination)
Instrument Type: Aglient 1260
Column: C18 25cm
Wavelength: 195nm
Method: HPLC-DAD/MS(for identification determination)
Instrument Type: Aglient 1260
Column: C18 25cm
Test Results
Putrescine-related Agmatine Sulfate has one impurity at
RRT about 1.14 with percent about 10% by normalization
calculation method. Furthermore, within MS identified
results, the major peak shows the Agmatine characteristic
ion segment (114.1 and 131.1). Whatsoever, the impurity
peak show 173.1 segment, which complies with the
molecular of Arcaine (1,4-diguanidinobutane, CAS#
544-05-8). Arcaine is a standard tool for setting up amnesia
animal models.
The purity test of AGMAPURE®
doesn’t show any
characteristic peak at all. It is Pure!!!

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No matter how accurately the process parameters are set and controlled, the byproduct Arcaine (1, 4-diguanidinobutane, CAS#:
544-05-8), a harmful chemical, always remains in the final Agmatine product unavoidably.
Let’s take a look at the reaction mechanism. Agmatine Sulphate is usually synthesized with Putrescine and S-Methylisothiourea by
chemical method, which gives Agmatine Sulphate as main product by controlling the equivalent of S-Methylisothiourea. The mechanism is
an addition-elimination reaction between the amino group of Putrescine and S-Methylisothiourea. But during the process of preparation of
Agmatine Sulphate, the amino group of the product Agmatine Sulphate can also react with S-Methylisothiourea to produce a small quantity
of Arcaine Sulphate as byproduct because of the material adding method and competitive reaction speed, which is very difficult to control in
organic process.
But for the biotransformation process of AGMAPURE®, the specificity of the utilized enzyme is in high efficiency, so there is no byproduct
produced during the process.
The table above is the purity analysis of two types of Agmatine Products with HPLC-UV method. The results are also distinct.
Arcaine is a harmful chemical to human brain. It’s a competitive antagonist of the polyamine binding site at the N-methyl-D-aspartic acid
receptor (NMDAR). As all know, memories are initially fragile, but become more stable with time. Such an observation has led to the
concept of memory consolidation, which refers to the stabilization of a new memory over time by neural processes activated by recently
learned information. The process of consolidation depends on glutamatergic transmission (da Rosa MM et al. 2012). The activation of
glutamatergic NMDAR in the hippocampus, amygdala and other brain areas play an important role in early consolidation of the memory. In
some researches (Raquele Kipper Mariani, et al. 2011), scientists prove the administration of Arcaine, by opioid mechanisms, blocks the
activation site of NMDAR, and impairs the memory performance!
Due to the technological limitations, Arcaine is introduced in almost all the Putrescine-related Agmatine Sulfate products. We have

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validated quite a few Putrescine-related Agmatine Sulfate products from different competitors with HPLC method. As expected, they all
contain the stubborn impurity: Arcaine, even the Agmatine Sulfate from Sigma (Cat#: A7127). According to many neurobiology researches,
Arcaine is the standard tool for setting up amnesia animal models. Therefore, we consider the introduction of Arcaine impurity in Agmatine
Sulfate will increase the risk of memory impairment.

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by GENABOLIX
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IV. Functions of Agmatine Sulfate
and the Mechanism
Agmatine is a ubiquitous naturally occurring
molecule (Tabor and Tabor 1984). It is
biosynthesized by decarboxylation of the amino
acid Arginine. Agmatine is found in low amounts
in many food stuff derived from plants, fish, and
animal products. Animal studies demonstrate
that the salt of Agmatine, Agmatine Sulfate, is
absorbed by the gastrointestinal tract and
distributed in the body (Molderings, Heinen et al.
2003). Agmatine initially attracted attention as an
endogenous ligand at imidazoline receptors and
α2-adrenoceptors (Li, Regunathan et al. 1994).
Independent of binding to those receptors,
Agmatine induces a variety of physiological and
pharmacological effects exhibiting a great
therapeutic potential.
Relations of the Arginine, Agmatine
and the Polyamine pathways

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-Agmatine Decreases blood pressure and heart rate
Agmatine as endogenous ligand of imidazoline and α2-adrenoceptors participates in the regulation of blood pressure and heart rate. The stimulation of imidazoline
and/or α2-adrenoceptors will suppresses the norepinephrine and epinephrine that mediate a number of physiological responses to endogenous catecholamines such as
hypotension, sedation, inhibition of insulin release, anti-lipolysis and platelet aggregation (Gonzalez et al., 1996, Zhao & Ren,2005). Also imidazoline and/or
α2-adrenoceptors are reported to related to reduction in calcium influx and potassium efflux, reducing the rate of depolarization and the amplitude of action potential in the
heart, through the inhibition the increase in the intracellular [Ca2+
] by blocking L-type voltage dependent Ca
2+
channel (Li et al., 1999) (Li et al.2000a, 2002a,b)
Finally, the decrease in systemic blood pressure in rats and rabbits after intravenous administration of Agmatine was sensitive to the nitric oxide synthase (NOS)
inhibitor L-NAME (Haulica et al.,1999), suggesting an involvement of nitric oxide (NO).
-Agmatine has antinociceptive effects
Agmatine binds to NMDA receptors and acts as an antagonist at NMDA receptor channels (Gadotti et al., 2006), and NMDA antagonists are known to block opioid
withdrawal symptoms (Trujillo & Akil, 1994). Agmatine reversed the up-regulation of the NR1 subunit of NMDA receptors in the nucleus accumbens inmorphine dependence
without changing NR1 subunit expression per se (Wang et al., 2011).
-Agmatine Represses the tumor cell growth
There is evidence that an impairment of intracellular agmatine homeostasis is crucially involved inmalignant cell proliferation in solid tumors and leukemia (Molderings et
al., 2004; Molderings, 2006; Wolf et al., 2007; Haenisch et al., 2008). In vivo, in human colon cancer tissue agmatine content and in parallel the expression of arginine
decarboxylase (ADC) were distinctly reduced compared with that in the normal tissue adjacent to the malignant tumor (Molderings et al., 2004). Decrease of intracellular
agmatine content by RNA interference targeting ADC in human intestinal tumor cells resulted in a significant increase of proliferation (Molderings, 2006).
-Potential diuretic
Agmatine can be formed and metabolized in rat kidney (Lortie et al., 1996). Administration of exogenous agmatine caused an increase in urinary flow rate by increasing
osmotic clearance and a cAMP dependent inhibition of urea absorption in the terminal rat inner medullary collecting duct, effects attributed to binding to imidazoline
recognition sites (Smyth & Penner, 1995; Penner & Smyth, 1996; Rouch & Kudo, 2002). Agmatine also produced renal vasodilatation and increases in nephron glomerular
filtration rate (Lortie et al., 1996; Schwartz et al., 1997). This effect was not altered by denervation (Lortie et al., 1996) and may be mediated via a constitutive NO synthase-
dependent mechanism, since it was abolished by the NO synthase inhibitors NG-monomethyl-L-arginine and nitro-L-arginine methyl ester (Schwartz et al., 1997).
-Agmatine boosts muscle pumps
Agmatine sulfate appears to boost muscle pumps in a couple different ways. First, Agmatine sulfate may improve nutrient partitioning, leading to more muscle glycogen
(carbohydrates stored in muscle tissue) stored and consequently more water retained in the muscle. This can lead to a full look to the muscle and increase muscle pumps.
Second, Agmatine sulfate also appears to increase nitric oxide production by acting as a competitive inhibitor of the enzyme nitric oxide synthase (Demady DR &
Jianmongkol S, et al.). The nutrient partitioning effects of agmatine may be due to its possible ability to increase the insulin response to carbohydrates, and it may also have
something to do with the increased blood flow to the muscle experienced with increased nitric oxide production. Agmatine sulfate may play a role in the hypothalamic control
of luteinizing hormone and growth hormone release, leading to increased levels of these hormones (Zarandi M & Serfozo P, et al.).

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V. Differences among Agmatine, L-Arginine and L-Citrulline
Agmatine, L-Arginine and L-Citrulline are all ingredients for bodybuilding products, but Agmatine is different from the other two
ingredients in many ways:
1) To achieve ideal functions, the oral dosage of Agmatine is much less than Arginine and Citrulline.
2) Besides the bodybuilding function, Agmatine also possesses potent ability as neuroprotectant and insulin modulator.
3) Although L-Arginine has multiple beneficial functions, its cost is actually expensive. Because after oral taken, 50%-75% of L-Arginine is
converted to Ornithine and urea instead of nitric oxide. If you want obvious effects, you need much more dose no matter in what form of salt
or ester it is.
4) L-Citrulline has some bodybuilding and pre-workout effects by converted to L-Arginine.
Ingredient
Recommended
Daily Dosage
Functions Mechanism
Agmatine 750mg~1000mg
√ Building muscle and body tissue
√ An intermediate product in the synthesis of
polyamines related to nitric oxide synthesis
√ Inducing the release of peptide hormones
√ Acting as a neuroprotectant
√ Stimulates the release of insulin and uptake of
calcium in pancreatic cells leading to improved insulin
sensitivity
√ Agmatine is an intermediate in polyamine
biosynthesis.
√ Agmatine is α2-adrenergic receptor agonist.
√ Agmatine is imidazoline receptor agonist.
√ Agmatine blocks some cation ligand-gated
channels to protect brain.
L-Arginine 6~9g
√ Building muscle and body tissue
√ Producing nitric oxide
√ Stimulating the secretion of growth hormone (at high
dosage)
√ Precursor for the synthesis of nitric oxide.
L-Citrulline 3~4g √ Building muscle and body tissue
√ Producing nitric oxide
√Precursor for the synthesis of L-Arginine.
VI. Implications of AGMAPURE®
In preclinical studies, low toxicity of Agmatine has been observed in cultured neurons (Gilad et al., 1996), as well as after intraperitoneal

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injection to rats (Satriano et al., 1998). In addition, Agmatine was taken in gram-doses for years in the US bodybuilding community
unrestrained as a putative effective dietary supplement to increase muscle mass and it is yet used in high doses in combination medicine as
an aphrodisiac without reported complications.
AGMAPURE®
is produced by natural biological process and it contains no putrescine-related impurity. Therefore, the application of
AGMAPURE®
as potential sports nutrition is much safer than any other putrescine-related Agmatine Sulfate product in the market. Besides
this advantage, supplementation with AGMAPURE®
may improve athletic performance, increase muscle size, fullness, and vascularity, and
may also increase fat loss. It may also have a couple of additional benefits like protection against free radical damage and an
antidepressant effect. All these implications show a really promising application prospect.
VII. Reference
Gadotti, V. M., Tibola, D., Paszcuk, A. F., Rodriques, A. L. S., Calixto, J. B., & Santos, A. R. S. (2006). Contribution of spinal glutamatergic receptors to the antinociception caused
by agmatine in mice. Brain Res 1093n, 116–122.
Gilad, G. M., Gilad, V. H., & Rabey, J. M. (1996). Arginine and ornithine decarboxylation in rodent brain: coincidental changes during development and after ischemia. Neurosci Lett
216, 33–36.
Gonzalez, C., Regunathan, S., Reis, D. J., & Estrada, C. (1996). Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery. Br J Pharmacol 119,
677–684.
Haenisch, B., von Kügelgen, I., Bönisch, H., Göthert, M., Sauerbruch, T., Schepke, M., et al. (2008). Regulatory mechanisms underlying agmatine homeostasis in man. Am J Physiol
Gastrointest Liver Physiol 295, G1104–G1110.
Haulica, I., Bild, W., Iliescu, R., Georgescu, R., & Frunza, F. (1999). Preliminary research on possible relationship of NO with agmatine at the vascular level. Rom J Physiol 36,
67–79.
Li, G., Regunathan, S., Barrow, C. J., Eshraghi, J., Cooper, R., & Reis, D. J. (1994). Agmatine: an endogenous clonidine-displacing substance in the brain. Science 263, 966–969.
Li, Q., Shang, Z. L., Yin, J. X.,Wang, Y. H., & He, R. R. (2002). Effect of agmatine on intracellular free calcium concentration in isolated rat ventricular myocytes. Acta Physiol Sin
54, 467–472.
Li, X. T., He, R. R., Liu, S., Liu, L. L., Zhang,W. L., Zhao, H., et al. (2000). Electrophysiological effects of agmatine on human atrial fibers. Life Sci 66, 2351–2356.
Li, X. T., Duan, H. R., & He, R. R. (2000). Inhibition by agmatine on spontaneous activity of rabbit atrioventricular node cells. Acta Pharmacol Sin 21, 931–935.
Lortie, M. J., Novotny, W. F., Peterson, O. W., Vallon, V., Malvey, K., & Mendonca, M. (1996). Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional

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Molderings, G. J., A. Heinen, et al. (2003). "Gastrointestinal uptake of agmatine: distribution in tissues and organs and pathophysiologic relevance." Ann N Y Acad Sci 1009: 44-51.
Molderings, G. J., Kribben, B., Heinen, A., Schröder, D., Brüss, M., & Göthert, M. (2004). Intestinal tumor and agmatine (decarboxylated arginine). Low content in colon carcinoma
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Wang, X. F., Wu, N., Su, R. B., Lu, X. Q., Liu, Y., & Li, J. (2011). Agmatine modulates neuroadaptations of glutamate transmission in the nucleus accumbens of repeated
morphine-treated rats. Eur J Pharmacol 650, 200–205.
Wolf, C., Brüss, M., Hänisch, B., Göthert, M., von Kügelgen, I., & Molderings, G. J. (2007). Molecular basis for the antiproliferative effect of agmatine in tumor cells of colonic,
hepatic, and neuronal origin. Mol Pharmacol 71, 276–283.
Zarandi M, Serfozo P, Zsigo J, Bokser L, Janaky T, Olsen DB, Bajusz S, & Schally AV. (1992). Potent agonists of growth hormone-releasing hormone. Part I. International Journal of
Peptide and Protein Research. 39(3), 211-7.
Kalra SP, Pearson E, Sahu A, & Kalra PS. (1995). Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone release in vivo and hypothalamic luteinizing
hormone-releasing hormone release in vitro. Neuroscience Letters. 194(3), 165-8.
Demady DR, Jianmongkol S, Vuletich JL, Bender AT, & Osawa Y. (2001). Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative
inactivation of the enzyme. Molecular Pharmacology. 59(1), 24-9.
da Rosa MM, Mello CF, et al. Opioid mechanisms are involved in the disruption of arcaine-induced amnesia by context pre-exposure. Neurobiol Learn Mem. 2012
Mar;97(3):294-300.
Raquele Kipper Mariani, Carlos Fernando Mello, et al. Effect of naloxone and morphine on arcaine-induced state-dependent memory in rats. Psychopharmacology (2011)
215:483-491.