What Is Agmatine?

Agmatine is a compound naturally formed from the amino acid L-arginine. It is a neurotransmitter found predominantly in neurons. Because it is capable of targeting multiple receptors, researchers are investigating it in the context of a spectrum of complex diseases.

Furthermore, some research suggests that agmatine may play a role in cognitive function, stress resiliency, mood, and athletic performance [R, R].

The highest levels of agmatine are found in the gut, where it is produced by the microbes living there. It is also found in dietary form, mainly in fermented foods, and in supplemental forms like agmatine sulfate. Agmatine is also produced in small amounts by mitochondria in the liver [R].

Mechanisms of Action

Agmatine is a natural component of the inner workings of many cells, and as such, it has complex interactions with cellular function. Researchers have been working to untangle agmatine’s mechanisms and effects by studying human and animal cells as well as bacteria.

Agmatine appears to block the production of NOS (nitric oxide synthase): There are 3 main enzymes that produce nitric oxide (NO); iNOS, nNOS, and eNOS:

• iNOS (inducible) produces large quantities of NO as a function of the immune system to kill harmful bacteria. If left unchecked, iNOS can cause inflammation.
• nNOS (neuronal) is a signaling molecule that facilitates communication in the brain across neurons. If left unchecked, nNOS can inhibit the growth and repair of neurons.
• eNOS (endothelial) signals vasodilation in the lining of blood vessels for increased blood flow. Increased blood flow lowers blood pressure and increases the import of oxygen and nutrients and export of cellular waste products.

Thus, some researchers believe agmatine may regulate nitric oxide levels by inhibiting iNOS and nNOS and increasing eNOS [R, R].

In other cell studies, agmatine has been found to:

• Block NMDA receptor: Agmatine binds to 2 sites of the NMDA (N-methyl-D-aspartate) receptor and prevents glutamate from binding to them. This may prevent neuron death from overexcitation due to the neurotransmitter glutamate [R].
• Activate alpha-2 adrenergic (α2A) receptors: Agmatine is strongly attracted to the alpha-2 adrenergic receptors. Low-dose agmatine amplifies α2A receptor activation while higher concentrations block it. Some effects of agmatine can be abolished with α2A receptor blockers, such as yohimbine and rauwolscine [R

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