Agmatine
Arginine-derived neuromodulator hitting NMDA and imidazoline targets, with a mood and pain support profile.
Pharmacology
Contents
WHAT IS AGMATINE?
Detailed overview
Agmatine is an endogenous neuromodulator formed by decarboxylation of arginine and sold as a dietary supplement in the form of agmatine sulfate. It acts on several targets at once: a weak NMDA receptor channel blocker, an imidazoline I1/I2 receptor agonist, an alpha-2 adrenoceptor modulator and an inhibitor of neuronal nitric oxide synthase, and it also behaves as an endogenous clonidine-displacing substance. Together these actions produce an antidepressant-like, analgesic and neuroprotective profile that is strongly supported by animal studies but only modestly in humans. A double-blind trial found agmatine sulfate effective in lumbar disc-associated radiculopathy, and an open-label pilot reported an antidepressant effect, but large confirmatory clinical trials are still lacking.
Mechanism
NMDA block + imidazoline agonism + nNOS inhibition
Evidence
Strong preclinical + small human pilots
Legal status
Dietary supplement (agmatine sulfate)
Receptor profile
- NMDA receptors (channel block)Moderate
- Imidazoline I1/I2 receptorsModerate
- Alpha-2 adrenoceptorsWeak
- Neuronal nitric oxide synthase (nNOS) inhibitionWeak
Safety
Side effects, stop signs, contraindications
Side effects · 4
- Mild digestive upset (nausea, diarrhea, bloating), especially at higher doses
- Mild blood pressure reduction from imidazoline and alpha-2 activity (possible dizziness)
- Changes in appetite or satiety (via polyamine metabolism)
- Uncertain long-term safety: human data are limited to small, short studies
Contraindications · 4
- Pregnancy and breastfeeding: safety not established, avoid
- Low blood pressure or antihypertensive medication: additive hypotension possible
- Combination with antidepressants (especially MAO inhibitors) requires medical supervision
- Not an approved medicine: sold as a dietary supplement, not to treat disease
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study
Shopsin B
Agmatine as a potential therapeutic intervention in bipolar depression: the preclinical landscape
Watts D, Pfaffenseller B, Wollenhaupt-Aguiar B, Paul Géa L, Cardoso TA, Kapczinski F
Evidence of Reduced Agmatine Concentrations in the Cerebral Cortex of Suicides
Chen GG, Almeida D, Fiori L, Turecki G
Altered Arginine/Agmatine Pathway and Polyamines in Adolescents Diagnosed with Major Depressive Disorder
Yazici KU, Ozturk ŞK, Percinel Yazici I, Ustundag B
Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy
Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM
FAQ
FAQ
Arginine-derived neuromodulator hitting NMDA and imidazoline targets, with a mood and pain support profile.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.