Agmatine - NOTE* This Topic Is Not Near Finished

08/29/2012 13:32



Protein synthesis suppression

"Polyamines have been demonstrated to play an important role in the transformation process. Conversely, polyamine depletion results in growth arrest" (9, 10).

"Polyamines are required components for both protein and nucleic acid synthesis"

"Herein we report concurrent suppression of both polyamine biosynthesis and transport by agmatine."


"Agmatine is absorbed from the gastrointestinal tract, probably by means of a specific transporter. It is likely that agmatine in the chyme of the gut represents an essential source of agmatine in the tissues of the organism. An increase in the availability of gastrointestinal agmatine for absorption impairs liver regeneration and may contribute to the development of liver diseases."


It would probably be a good idea to leave agmatine out of the NO products, since it's an endogenous, competitive inhibitor of NOS.[/B] :D



"When inhibitors of polyamine biosynthesis are present and polyamine levels are low, [B]the rates of protein and nucleic acid synthesis are diminished[/B] [14,15], fidelity of translation is impaired [16] and chromosome disintegration may occur [17,21]."

"Polyamines are essential, low-molecular-weight organic cations that have been implicated in the biosynthesis of nucleic acids and proteins (25)." "Polyamine depletion also decreases general protein synthesis [5,38]."

[5] - Marton, L. J. and Morris, D. R. (1987) in Inhibition of Polyamine Metabolism

[14] - Whitney, P.A. and Morris, D.R. (1978) J. Bacteriol. 134, 214-220  

[15] - Jain, A. and Tyagi, A.K. (1987) Moll. Cell. Biochem. 78, 3-8

[16] - Koza R.A. and Herbst, E. (1992) Biochem. J. 281, 87-93

[17] - Knutila, S. and Pohjanpeto, P. (1983) Exp. Cell Res. 145, 222-226

[21] - Palvimo, J., Pojanpeto, P., Kankkurer, A.L. and Maenp, P.H. (1987) Biochim. Biophys. Acta 90, 21-29

[38] - Heby, O. (1981) Differentiation 19, 1?20



(1) DNA binding and protein synthesis

(2) Mediation of cell growth/cell death

(3) Hypusine synthesis (which is essential for cell survival/proliferation)

(4) Development and differentiation of the central nervous system

(5) Inward rectification of potassium channels

"Alright everyone. Just wanted to post up some information as i know a lot of you have been using agmatine for nutrient partioning, and pumps ect. This thread is not meant to deter anyone, nor say its a good or bad product. Im a Science guy, i read all the time and when i come across interesting articles, i tend to share them and love hearing feedback and discussion. This is how we all learn.

I specifically messaged coop about this because he is highly respectable, and has great knowledge. Im hoping this can lead to civil discussion where people can take what they want from it.

Agmatine study in rats

Essentially this study had a few groups with agmatine and rats were givin IP shots of the Agmatine. They recorded food intake and Alpha2 activity.

The study showed that in HIGHER doses, NPY/AgRP levels (hunger signals, carb cravings) were higher. They showed increased appetite and an orexigenic effect. The Amount of food was then tested when agmatine was given with yohimne and still showed an increase yet, Yohimbine attenuated npy plus agmatine stimulated feeding by 30%

"based on these findings, Agmatine reduces noradrenaline activity in the PVN via pre synaptic a2- adrenoreceptors, which in turn may promote the release of NPY and consequently stimulate eating"

Theres a lot more in the study, but these were in RATS, and they were injkections. But ive seen people taking up to 2g per day.

i think this is a good reading especially with summer coming up.... Pump is nice, but when it can come at the expense of an increased food intake and agonism of alpha 2s id be worried.

This can go hand in hand with what dan duchain said in Bodyopus.... Low calorie dieting can increase alpha 2 receptors. Increases in NPY and AgRP can influence Alpha-2 adrenos, and slow metabolism... This can be shown by rT3 levels.

increased NPY/AgRP with depressed leptin, increases alpha 2 agonism, and increased food intake can be a cause for disaster in some people

When N{PY/AgRP are raised there becomes issues with thyroid...

Theres definitely other mechanisms in here. but i just put down some kind of messy to post this thread."




You forgot the effects it has on the NMDA (antagonist) and on the adreno receptors (On one hand it can be a partial agonist which may increase fat loss or it could be partial antagonist which would halt fat loss)

Recently this has been the latest craze on the forums. It is sort of the flavor of the month so to speak. It is mainly marketed as something to induce "teh pumps!" but from the looks of it to me, it comes with a couple negatives.

Agmatine: Biological Role and Therapeutic Potentials in Morphine Analgesia and Dependence

Agmatine is an amine that is formed by decarboxylation of L-arginine by the enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to putrescine. Agmatine binds to several target receptors in the brain and has been proposed as a novel neuromodulator. In animal studies, agmatine potentiated morphine analgesia and reduced dependence/withdrawal. While the exact mechanism is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, α2-adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP) signaling have been proposed as possible targets. Like other monoamine transmitter molecules, agmatine is rapidly metabolized in the periphery and has poor penetration into the brain, which limits the use of agmatine itself as a therapeutic agent. However, the development of agmatinase inhibitors will offer a useful method to increase endogenous agmatine in the brain as a possible therapeutic approach to potentiate morphine analgesia and reduce dependence/withdrawal. This review provides a succinct discussion of the biological role/therapeutic potential of agmatine during morphine exposure/pain modulation, with an extensive amount of literature cited for further details.
FT -

Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors.

It has been suggested that agmatine (decarboxylated arginine) is an endogenous clonidine-displacing substance (CDS) which recognizes 2-adrenoceptor and non-adrenoceptor, imidazoline binding sites. We have examined the effect of agmatine at 2-adrenoceptor binding sites and pre- and postjunctional 2-adrenoceptors. Agmatine produced a concentration-dependent inhibition of 1 nmol/l 3H-clonidine binding to both rat (pKi–5.10+-0.05) and bovine (pKi–4.77+-0.38) cerebral cortex membranes. However, agmatine (0.1–100 M) failed to activate pre-junctional 2-adrenoceptors regulating transmitter release in the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate post-junctional 2-adrenoceptors of the porcine isolated palmar lateral vein which mediate contraction or inhibition of forskolin-stimulated cyclic AMP formation. High concentrations of agmatine (10–30-fold the pKi at 2-adrenoceptor binding sites) failed to influence 2-adrenoceptor activation by either clonidine or UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate) in any of the peripheral preparations examined. Moreover, even in a preparation where an interaction with 2-adrenoceptor binding sites on cell membranes can be demonstrated, the rat cerebral cortex, agmatine failed to inhibit forskolin-stimulated cyclic AMP in the intact tissue or affect the inhibition produced by the selective 2-adrenoceptor agonist UK-14304. Agmatine was also devoid of agonist activity in two preparations, the rat isolated thoracic aorta and the rat isolated gastric fundus, in which CDS has been reported to produce non-adrenoceptor effects. Thus, we have confirmed that agmatine recognizes 2-adrenoceptor binding sites and, therefore, is a CDS. However, since agmatine is devoid of pharmacological activity at either peripheral or central 2-adrenoceptors it can not account for earlier reports suggesting that brain-derived CDS can activate 2-adrenoceptors.
Cardiovascular responses to agmatine, a clonidine-displacing substance, in anesthetized rat.

We investigated the cardiovascular responses in anesthetized ventilated rats to agmatine (decarboxylated arginine), an amine which is an endogenous clonidine-displacing substance (CDS) synthesized in brain. Intracisternal agmatine dose-dependently increased sympathetic nerve activity and arterial pressure (at 400 nmol by 8.7 +/- 2.1 microV and 28.6 +/- 2.7 mmHg, respectively) and blocked arterial baroreflex reflexes. Microinjection of agmatine into the rostral ventrolateral medulla (RVL) had no effect on arterial pressure or sympathetic nerve activity while iontophoresis of agmatine onto defined vasomotor neurons of RVL was also without effect. Agmatine (i.v.) decreased sympathetic nerve activity and arterial pressure probably by blocking the transmission through sympathetic ganglia and by direct dilation of vascular smooth muscles. Despite binding like clonidine to alpha 2-adrenergic receptors and imidazoline (I)-receptors of both classes, agmatine does not replicate the central or peripheral actions of clonidine. The results suggest that earlier cardiovascular actions of partially purified CDS were either attributable to contaminating molecules and/or that CDS may be a family of molecules.
Cardiovascular effects of agmatine, a "clonidine-displacing substance", in conscious rabbits.

Agmatine has been identified as a "clonidine-displacing substance" in extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by alpha 2-adrenoceptors. In conscious rabbits, agmatine 10 micrograms kg-1 injected intracisternally (i.c.) caused no change, whereas agmatine 30, 100 and 300 micrograms kg-1 i.c. increased renal sympathetic nerve firing, the plasma concentration of noradrenaline and adrenaline and arterial blood pressure. Heart rate tended to be decreased. Yohimbine 1.5 micrograms kg-1 i.c. caused no change, whereas yohimbine 5, 15 and 50 micrograms kg-1 increased renal sympathetic nerve activity, the plasma concentration of noradrenaline and adrenaline, blood pressure and heart rate. In rabbit brain cortex slices preincubated with [3H]-noradrenaline, agmatine 1 to 100 microM did not modify the electrically evoked overflow of tritium (either 4 pulses at 100 Hz or 36 pulses at 3 Hz). The evoked overflow was reduced by 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304) 0.03 to 30 nM (4 pulses at 100 Hz), and this inhibition was not affected by agmatine 10 and 100 microM. Agmatine did not change the basal efflux of tritium. The results show that agmatine, like yohimbine, causes central sympathoexcitation when given i.c., but agmatine differs from yohimbine in that it does not increase heart rate. Agmatine acts neither as an agonist nor as an antagonist at the alpha 2-autoreceptors in rabbit brain cortex. alpha 2-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Agmatine: an endogenous clonidine-displacing substance in the brain.

Clonidine, an antihypertensive drug, binds to alpha 2-adrenergic and imidazoline receptors. The endogenous ligand for imidazoline receptors may be a clonidine-displacing substance, a small molecule isolated from bovine brain. This clonidine-displacing substance was purified and determined by mass spectroscopy to be agmatine (decarboxylated arginine), heretofore not detected in brain. Agmatine binds to alpha 2-adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells. Its biosynthetic enzyme, arginine decarboxylase, is present in brain. Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter.
So it is an antagonist for NDMA receptor and agonist for the alpha 2

Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery.

1. We investigated the vascular effects of agmatine (decarboxylated arginine), an endogenous ligand for alpha 2-adrenoceptors and non-adrenoceptor imidazoline (I-) receptors, present in endothelium, smooth muscle and plasma, using the rat tail artery as a model. 2. While by itself agmatine (10 nM-1 mM) was without effect on isolated arterial rings, at the highest concentration used (1 mM) it slightly increased EC50 values for contractions elicited respectively by the alpha 1- and alpha 2- adrenoceptor agonists methoxamine and clonidine. 3. Agmatine (0.03-1 mM) produced a concentration-dependent transient inhibition of the contractions induced by transmural nerve stimulation (TNS; 200 mA, 0.2 ms, 1 Hz, 10 s). This effect was abolished by the alpha 2-adrenoceptor antagonists, rawolscine and idazoxan. 4. In the presence of rawolscine or idazoxan, agmatine produced a concentration-dependent delayed facilitation of TNS-induced contractions, which was prevented by cocaine. 5. Neither inhibitory nor potentiating actions were produced by agmatine on contractions induced by noradrenaline (NA) administration. 6. Agmatine did not directly affect [3H]-NA uptake in bovine cultured chromaffin cells. 7. Agmatine can regulate vascular function by two opposing actions at sympathetic nerve terminals, with different latencies: a transient inhibition of NA release mediated by prejunctional alpha 2-adrenoceptors and a cocaine-sensitive delayed facilitation the mechanism of which is undetermined at present. 8. The results reveal the existence of a novel endogenous amine modulating NA release in the perivascular sympathetic terminals.
And also looks like agmatine can inhibit NA release (agonizes Aplha 2)

Combine these with its potential to increase hunger hormones NPY/AgRP and you have the reasons why I dont mess with it.