Agmatine SulfatevsALCAR

Agmatine is a polyamine neuromodulator with multiple targets: (1) NMDA receptor antagonist at the polyamine binding site (GluN1/GluN2B) — reduces excitotoxicity, pain signaling, and blocks the receptor's open channel. (2) Imidazoline I1 and I2 receptor agonist — I1 in the rostral ventrolateral medulla reduces sympathetic tone; I2 modulates monoamine oxidase and provides anxiolytic/antidepressant effects. (3) Selective nNOS (neuronal nitric oxide synthase) inhibitor — reduces peroxynitrite formation and oxidative stress while preserving eNOS (endothelial) function for vascular health. (4) Alpha-2 adrenergic receptor agonist — reduces norepinephrine release from locus coeruleus, promoting calm. (5) Modulates opioid receptors — enhances mu-opioid analgesia, potentiates delta-opioid, and may reduce tolerance via nitric oxide and NMDA mechanisms.

ALCAR crosses the blood-brain barrier via the organic cation transporter (OCTN2) more effectively than L-carnitine. In neurons, it is hydrolyzed by carnitine acetyltransferase to donate its acetyl group to coenzyme A, forming acetyl-CoA—which can then be used for acetylcholine synthesis via choline acetyltransferase, effectively providing raw material for the memory neurotransmitter. ALCAR also transports long-chain fatty acids across the inner mitochondrial membrane via the carnitine palmitoyltransferase system for beta-oxidation and ATP production. ALCAR activates nerve growth factor (NGF) signaling, possibly through modulation of NGF receptor (TrkA) expression or downstream MAPK/ERK pathways. It has antioxidant properties, reducing lipid peroxidation in mitochondrial membranes and scavenging free radicals. These mechanisms support cognitive function and neuroprotection.