Agmatine is a metabolite of L-Arginine.

It shows promise for alleviating neuropathic pain and drug addiction. Agmatine supplementation can also protect from strokes and benefit cognitive health.

Agmatine is derived from L-arginine through decarboxylation (the removal of a carboxylic acid group). It is stored in neurons and is released during neuronal activation. Agmatine is considered to be a neurotransmitter and neuromodulator.

Preliminary research suggests agmatine has potential use in the treatment of neuropathic pain and drug addiction. It also protects the brain from toxins and strokes.

Though supplementing agmatine by itself can increase the perception of pain, it works synergistically with painkillers like morphine and fentanyl. Agmatine’s synergy with opioids allows it to reduce pain killer tolerance, the possibility of addiction, and pain itself.

Agmatine has several mechanisms. It can inhibit N-methyl-D-aspartate (NMDA) and nicotinic acetylcholine receptors, as well as activate imidazoline receptors. Agmatine can also inhibit nitric oxide synthase enzymes, which allows it to regulate elevated levels of nitric oxide. Agmatine can inhibit calcium channels and certain serotonin receptors as well. Further research is needed to determine the full extent of agmatine’s mechanisms.

There is a lot of animal evidence to suggest agmatine is a highly promising research chemical. It is not a common supplement because there is a lack of human evidence for its effects. Several studies have been done on people, but the majority use agmatine injections, not oral ingestion. Research must establish that agmatine’s effects will work following oral ingestion in order for wide-scale supplementation to be considered.


Nutrient-Nutrient Interactions



L-Arginine and L-Citrulline are two amino acids that raise plasma arginine concentrations.

Agmatine’s oxidative inactivation of the nitric oxide synthase enzyme (seen in this study with nNOS with a Ki of 29µM) is due to increasing the activity of the NADPH oxidase subunit[116] which arginine is known to hinder for nNOS[117][118] yet appears to increase activity for iNOS and eNOS.[346][117] In this sense, arginine is antagonistic to the effects of agmatine towards nNOS (a possible reason why supplemental arginine inhibits many neurological effects) but does not affect eNOS in the same manner.

It is not sure whether pairing either of these two agents with arginine will enhance systemic nitric oxide production (via eNOS; the mechanism underlying most of the blood pressure effects) or be antagonistic; both are plausible, with the former being due to increased nitric oxide production from eNOS and the latter due to quicker inactivation of the enzyme.

Arginine (and by extension, citrulline) are inhibitory to some of the neurological effects of agmatine supplementation such as reducing opioid tolerance. The interaction between agmatine and arginine in regards to blood vessels (and ‘the pump’ for physical exercise) is not clear.


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