Agmatine

links: Nootropics reference: https://www.reddit.com/r/NooTopics/comments/mwc4yz/agmatine_sulfate_miracle_substance_with_endless/ 4-13-2021

Agmatine #

An ‘aminoguanidine’. Naturally produced and involved in quite a few pathways in brain and body. Derived from Arginine decarboxylation.

• MAO reuptake inhibitor (the opposite of an MAOI)
• Lowers COX-2, potentiates CB1.
• 5-HT1A agonist, nAChR antagonist
• H3 agonist?
• Increases eNOS, but decreases iNOS and nNOS. I think this is by means of NMDA inhibition.
  • Oxidative stress-induced nNOS deactivation: Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme I mean, I wonder if it’s a net negative in terms of NOS activity?
    • We discovered that agmatine causes a 3-fold increase in the NADPH oxidase activity of nNOS leading to the production of H2O2 and is a likely cause for the inactivation of the enzyme
  • Polyamines inhibit nitric oxide synthase in rat cerebellum
    • Spermine > spermidine > putrescine inhibited NOS.
    • These inhibitory effects … were also observed in intact cultured cerebellar granule neurons upon stimulation of NMDAR. Evidence was obtained, however, that endogenous polyamines are not involved in regulation of NMDA-stimulated NO synthase activity.
      • This makes sense as a negative feedback loop
• Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice
  • Enhances the effect of bupropion 10-fold? tf? Being a polyamine site antagonist supposedly lets it preferentially antagonize eNMDAR. Spermidine is actually an agonist. According to sirsad.
• Agmatine acts as an antagonist of neuronal nicotinic receptors.
• Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway
  • In ‘chronic unpredictable mild stress’ (CUMS): Inhibits Acetylcholinesterase, significantly increases BDNF and inhibits corticosterone. Showed significant antidepressant activities.
• Antidepressant-like effect of agmatine and its possible mechanism
  • Attenuates depression-induced decrease in monoamine levels. Monoamines including NE, E, DA, or 5-HT in PC12 cells decreased after the treatment with 200 microM NMDA for 24 h, while in the presence of 1 and 10 microM agmatine or 1 and 5 microM desipramine, the levels of NE, E, or DA were elevated significantly while 5-HT did not change.
• 5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate cyclase activation in the mice brain are involved in the antidepressant-like action of agmatine
  • Its effects were antagonized by co-administration of by pindolol (antagonist of β-adrenergic, 5-HT1A/5HT1B), yohimbine (α2 adrenergic receptor antagonist), and Tropisetron.
• Can inhibit certain Serotonin receptors.
• Increases NRF2 R
• Increases Adenylyl Cyclase in the prefrontal cortex, and decreases levels of AC which associate with depression
• May help promote/support: positive emotional outlook, restful sleep, immune system function, strength and endurance, gastric motility and digestion, cognitive function cardiovascular function, pain tolerance, and recovery.
• Post-training administration increases spatial memory consolidation in rats
• Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors
  • 
• Evidence for imidazoline receptor involvement in the agmatine antidepressant-like effect in the forced swimming test

The molecular and metabolic influence of long term agmatine consumption (Nissim et al., 2014) #

Great overview. The thing about this study though is like - is a very healthy person not gonna see some of these benefits especially if they get a lot from foods? I think it’s sort of a trace one though. But yeah these results are very based

• Activates PPAR-α/its coactivator PGC1α, increased PPAR-γ expression, and expression of genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis/transport. Increased Beta-oxidation Allow me to spam these big ass graphs. These are really the main ones I care about
• HFD = high fat diet; (60% vs 10%) SD = control

Supplementation #

• Dose: 500mg-1-2g or so, twice a day.
  • 2g/day for a year permanently cured sirsadalot’s depression. Dand recommends 3g
• Timing: 2-hour half life
• Not absorbed well when taken with protein, as it uses the same transporters as Arginine (thus inhibits its absorption as well)