Agmatine

Agmatine ((4-aminobutyl)guanidine) is the decarboxylation product of the amino acid arginine and is an intermediate in polyamine biosynthesis. It is discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to α2-adrenergic receptor and imidazoline binding sites, and blocks NMDA receptors and other cation ligand-gated channels. Agmatine inhibits or inactivates nitric oxide synthase (NOS), and it induces the release of some peptide hormones.

History
The term "agmatine" was coined in 1910 by Albrecht Kossel, the German scientist who first identified the substance in herring sperm. Most probably the word stems from A- (for amino-) + g- (from guanidine) + -ma- (from ptomaine) + -in (German)/-ine (English) suffix with insertion of -t- apparently for euphony.

Effects on nitric oxide synthase (NOS)
An in vitro study found that agmatine was a competitive inhibitor of NOS, with enzyme-inhibitor concentrations (Ki) 660 &mu;M for NOS I (neuronal NOS), 220 &mu;M for NOS II (inducible NOS), and 7.5 mM for NOS III (endothelial NOS). Another study determined that concentrations of agmatine on the order of 29 &mu;M effect an irreversible, time- and concentration-dependent inactivation of NOS I. The same study noted a threefold increase in NADPH oxidase activity and accompanying oxidative stress via H2O2 production.

Neuroprotective effect
Treatment with exogenous agmatine exerts neuroprotective effects in animal models of ischemia and neurotrauma.

Antidepressant potential
A recent study shows that agmatine administered orally abolished the depressive-like behavior induced by the administration of the pro-inflammatory cytokine, tumor necrosis factor (TNF-α) in mice.

Another study shows that oral agmatine exerts antidepressant like effects via NPYergic system possibly mediated by the NPY Y1 receptor subtypes in rats. Two earlier studies from the same author show that activation of the δ-opioid and μ-opioid receptor and the 5-HT1A, 5-HT1B and 5-HT2 receptors are important for the antidepressant effect of agmatine.

Two other studies in mice show that agmatine binding to the imidazoline receptor is involved in the antidepressant action of both NDRI bupropion and the SSRIs fluoxetine and paroxetine. Indeed, another study suggests that the anti-immobility effect of agmatine in the forced swimming test is dependent on its interaction with imidazoline I1 and I2 receptors.