What is Agmatine?
Agmatine is a derivative of the amino acid arginine. It is a biogenic amine also produced by the neurons of the central nervous system (brain) and stored in the related synaptic vesicles, where it is fortified by uptake, released by depolarization and subsequently inactivated by the enzyme agmatinase. In the human brain, agmatine appears to act as a neuromodulator / neurotransmitter by binding to different receptor targets; in experimental models it has also shown interesting neuroprotective effects.
Agmatine is obtained from the decarboxylation of arginine by the enzyme arginine-decarboxylase, but its synthesis is NOT aimed at itself as it is an intermediate of polyamines (cell growth factors). The same reaction is carried out by the intestinal bacterial flora on the food residues containing arginine, whose biotransformation into agmatine (in turn converted into putrescine) contributes to giving the faeces the characteristic and unpleasant odor.
Functions
Agmatine is a biological regulator and acts as a real neurotransmitter / neuromodulator; the functions of agmatine are (or rather, THEY SHOULD BE) of:
- * BLOCK (ANTAGONISM) of post-synaptic receptors for NMDA ( N-Methyl-D-Aspartate ), whose physiological agonist is glutamic acid; the stimulation of these receptors has the effect of increasing the entrance of sodium and especially calcium into the neurons, followed by the setting up of various processes:
- activation of nitroxide-synthetase which produces nitric oxide (NO) as responsible for the synthesis of cyclic-GMP in nerve endings; therefore, agmatine inhibits the synthesis of nitric oxide, but despite this it seems to have vasodilatory and hypotensive effects
- activation of a protein kinase C that regulates the blockage of magnesium (Mg).
- activation of ornithine-decarboxylase which promotes the synthesis of polyamines by enhancing the influx of calcium (Ca)
- activation of phospholipase A2 which determines an enhancement of presynaptic release and an inhibition of the glial uptake of glutamic acid (an exciting neurotransmitter and precursor of GABA or γ-aminobutyric acid; the latter is a regulator of neuronal excitability and is directly involved in the maintenance of muscle tone).
- Binding α2-adrenergic receptors : their activation causes a decrease in the production of norepinephrine (negative feedback) and of the secretion of insulin at the pancreatic level. Nevertheless, the overall effect of agmatine would seem to favor the release of catecholamines from chromaffin andrenergic cells (Li et al ., 1994), and insulin from pancreatic B-cells (Sener et al ., 1989)
- Bind imidazoline and nicotinic receptors
- Promote the release of peptide hormones such as: GH ( somatotropin - anabolic hormone) and LH ( luteotropin - stimulating the release of testosterone - anabolic hormone).
- Similar to nitric acid, it causes vasodilation and increases the glomerular filtration rate; the researchers have in fact noticed how the arginine infusion causes an increase in glomerular filtration even when nitric oxide synthase is inhibited; this effect, however, does not occur when the enzyme arginine decarboxylase is inhibited.
Agmatine and arginine supplements
Agmatine is therefore an amino acid derivative of arginine, which for its real or presumed functions is used as an ingredient of some arginine-based products aimed at increasing endothelial nitric oxide (ON) (read the dedicated article: Nitric oxide).
The goal of the addition of agmatine to promote the synthesis of nitric oxide is to block the ENDOGENOUS transformation of arginine into agmatine, consequently implementing the bioavailability of arginine for the production of nitric oxide.
In fact, the enzyme arginine decarboxylase is inhibited by calcium ions and polyamines, so agmatine is a feedback inhibitor of this enzyme (an effect necessary to avoid an excessive accumulation of agmatine in the synthesis site).
Based on this theory, the significant presence of exogenous agmatine would affect the metabolic destination of arginine, directing it more towards the production of nitric oxide rather than on its conversion into endogenous agmatine.
Furthermore, agmatine is used for its presumed anti-depressive activity (Zomkowski et al ., 2002; Taksande et al ., 2009), anti-pain (Onal et al ., 2004), anxiolytic (Lavinsky et al ., 2003), anticonvulsant (Bence et al ., 2003), anti-proliferative (Isome et al ., 2007), neuroprotective (Olmos et al ., 1999), facilitating spatial memory (Liu and Bergin, 2009) and stimulus on secretion of insulin and other anabolic hormones (GH and Testosterone). Often, in informative articles to push the relative commercial products, all these alleged beneficial effects are exalted and fed to the reader without the slightest criticality, omitting to underline how these are still preliminary evidences.
Side effects
Agmatine is a molecule still little known and studied; there are no known side effects related to its intake but it is well known that arginine supplements (in which agmatine is present) are potentially allergenic (symptoms: respiratory complications, rashes, burning and itching). In mice, agmatine has been shown to increase caloric intake and dietary preference for carbohydrates in satiated rats (Prasad and Prasad, 1996); this could facilitate an unwanted increase in appetite, and therefore in weight, in the user.
For greater safety, before taking supplements with agmatine, consult your doctor and verify the possible biochemical interaction with the drugs used for any therapeutic combination.
