Inhibition of protein arginine ADP-ribosylation. Matrix metalloproteases (MMPs). Indirect down-regulation of the enzymes MMP 2 and 9. Advanced glycation end product (AGE) formation. Direct blockade of AGEs formation. NADPH oxidase. Activation of the enzyme leading to H2O2 production. Food consumption Agmatine sulfate injection can increase food intake with carbohydrate preference in satiated, but not in hungry rats and this effect may be mediated by neuropeptide Y. However, supplementation in rat drinking water results in slight reductions in water intake, body weight and blood pressure. Also force feeding with agmatine leads to a reduction in body weight gain during rat development. Also, many fermented foods contain agmatine. Pharmacokinetics Agmatine is present in small amounts in plant-, animal-, and fish-derived foodstuff and gut microbial production is an added source for agmatine. Oral agmatine is absorbed from the gastrointestinal tract and readily distributed throughout the body. Rapid elimination from non-brain organs of ingested (un-metabolized) agmatine by the kidneys has indicated a blood half life of about 2 hours. Also, agmatine is a neuro-modulator, which means it is a substance that modulates chemical transmission of information between the nerve cells. Research A number of potential medical uses for agmatine have been suggested. Cardiovascular Agmatine produces mild reductions in heart rate and blood pressure, apparently by activating both central and peripheral control systems via modulation of several of its molecular targets including: imidazoline receptors subtypes, norepinephrine release and NO production. Glucose regulation Agmatine hypoglycemic effects are the result of simultaneous modulation of several molecular mechanisms involved in blood glucose regulation. Kidney functions Agmatine has been shown to enhance glomerular filtration rate (GFR) and to exert nephroprotective effects. Neurotransmission Agmatine has been 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 receptor binding sites, and blocks NMDA receptors and other cation ligand-gated channels. However, while agmatine binds to α2-adrenergic receptors, it exerts neither an agonistic nor antagonistic effect on these receptors, lacking any intrinsic activity. Short only of identifying specific ("own") post-synaptic receptors, agmatine in fact, fulfills Henry Dale's criteria for a neurotransmitter and is hence, considered a neuromodulator and co-transmitter. The existence of theoretical agmatinergic-mediated neuronal systems has not yet been demonstrated although the existence of such receptors is implied by its prominence in the mediation of both the central and