Agmatine is an amino acid supplement and neuromodulator that is sometimes classified as a neurotransmitter as well. It functions as a nootropic as well as a longevity supplement, especially for the brain. Agmatine is closely connected to the amino acid l-arginine and, like most nootropics, is considered highly non-toxic. That said, due to insufficient toxicology studies it is recommended to stay below the range of 2,670mg dosage. In addition to it’s nootropic activity it seems to enhance or potentiate several other types of substances including antidepressants such as Buproprion, opioidergic pain killers and cannabinoids such as marijuana due to it’s modulatory effect on the endogenous cannabinoid system, especially the CB1 receptor.
Despite being a derivative of the amino acid l-arginine it shouldn’t be mixed with either l-arginine or l-citrulline due to possible neurological side effects and possible cardiovascular interactions. Yohimbine and Rauwolscine are also definitely not to be mixed. Agmatine activates the α2A receptor (part of the adrenergic, “fight or flight” system) in the brain that yohimbine and rauwolscine inhibit. D-aspartic acid is another to avoid due to the NMDA receptor signaling reduction that occurs. Drinking alcohol with agmatine is also to be avoided. Coingestion of agmatine and alcohol increases the possibility of ulceration.
There hasn’t been enough human clinical testing done to determine a perfect dosage range or therapeutic window for agmatine yet, but in one human study 1300-2670mg of agmatine was used daily to treat neuropathic pain. 1.6 – 6.4mg/kg is the estimated dose in humans for cognitive enhancement. That would be equal to around 217-435mg in a 150lb person.
Due to the fact that agmatine isn’t readily absorbed with protein, it should be taken before a meal. The absorption issue is due to the fact that agmatine uses the same transporter pathways as its parent compound l-arginine. According to at least one in vitro study in rodents, it was discovered that 1-3% of agmatine was metabolized into GABA (the brain’s natural calming compound and the primary inhibitory neurotransmitter in the body and brain). Agmatine appears to be readily absorbed following oral ingestion but more studies are needed to determine if the same results found in rats would be present in humans via an oral route. Interestingly enough, the half life of agmatine in the body seems to be rather short-lived despite a much longer circulation within the brain itself.
Agmatine has been referred to as a neuromodulator compound and is considered by some to be a relatively new neurotransmitter in its own right. Like other neurotransmitters, its metabolism is regulated throughout the nervous system and is stored in the presynaptic portion of the neuron. As a neuromodulator it’s been shown to positively modulate signaling through the NMDA (n-methyl d-asparte). NMDA is closely related to glutamate, the brain’s primary excitatory neurotransmitter. NMDA is closely related to memory function as well as synaptic plasticity. Neuroplasticity is the ability of the brain to organize and reorganize itself which is thought to be vital to learning and memory functions. Agmatine has a modulatory effect on NMDA receptors, the α2 adrenergic receptors as well as serotonergic receptors.
It is theorized that agmatine could possibly be an agonist of acetylcholine’s nicotinic subreceptor set. Agmatine doesn’t appear to affect serotonin itself or its release directly, however, the anti-depressant quality of agmatine seems unchanged even when serotonin level is depleted by up to 70%. Despite its antidepressant effect being unrelated to serotonin levels, blocking the certain serotonergic subreceptors seems to inhibit agmatine’s antidepressant effects
Agmatine also has an effect on the endogenous cannabinoid systems. Endocannabinoids (CB1 and CB2) are closely related to the chemical THC, found in marijuana. Agmatine seems to have some pain killing effect, particularly in in regard to neuropathic pain. Agmatine was ineffective in reducing thermal pain perception based on a rodent study involving hot plates, but was synergistic and potentiated the analgesic (pain-killing) effect of two cannabinoidergic drugs by 300-440%. In addition to the potentially cannabinoidergic neuropathic analgesia agmatine seems to have some opioidergic effects.
Agmatine is a bacterial byproduct of arginine and is found in some fermented foods including wine, beer, and even instant coffee. The concentration of agmatine in these products is negligible as far as effects are concerned, however. Agmatine may activate imidazoline receptors as well. This is correlated with an increase in β-endorphin which helps the pancreas with insulin secretion which may benefit bodybuilders. Insulin increase may support lean, muscle growth.
Agmatine also has anti-hypertensive properties (blood pressure lowering) so for hypotensive persons care should be taken. It may also be a promising neuroprotector for stroke pre-treatment.Agmatine also seems to increase BDNF (brain derived neurotrophic factor) which is involved in learning and memory functions.
As far as bodybuilding goes it seems to increase muscle pumps via inhibition of NOS (nitric oxide synthase), increases workout energy and output, improves mental clarity and focus and increases appetite (even when full) which could make the task of “bulking up” easier.
With agmatine or any other supplement, it’s always best to speak with your personal care practitioner first, especially if you’re currently under a doctor’s care for any existing condition or taking any over the counter or prescription drugs.