Alpha-GPCvsHuperzine A

Alpha-GPC (L-alpha-glycerylphosphorylcholine) is hydrolyzed by phospholipases in the gut and brain to release free choline, which is transported across the blood-brain barrier via the choline transporter (CHT1) and taken up by neurons for acetylcholine synthesis via choline acetyltransferase (ChAT). It is the most efficient oral choline source for raising brain acetylcholine levels due to high bioavailability and direct utilization. Alpha-GPC also provides glycerophosphate (glycerol-3-phosphate), which enters the Kennedy pathway and supports phosphatidylcholine and cell membrane phospholipid synthesis. It may stimulate growth hormone release through cholinergic activation of the pituitary. Alpha-GPC enhances high-affinity choline uptake and supports muscarinic (M1, M2) and nicotinic receptor function.

Huperzine A is a potent, selective, and reversible inhibitor of acetylcholinesterase (AChE), binding to the enzyme's active site and preventing hydrolysis of acetylcholine to choline and acetate. By blocking AChE, it increases acetylcholine concentration in the synaptic cleft, prolonging activation of muscarinic (M1-M5) and nicotinic receptors. Huperzine A also blocks NMDA glutamate receptors in a non-competitive, use-dependent manner (similar to memantine), binding to the phencyclidine site within the ion channel and protecting neurons from excitotoxic calcium influx. It shows selectivity for the NR2A and NR2B subunits. Additionally, huperzine A has antioxidant properties, scavenging reactive oxygen species and reducing lipid peroxidation. It may enhance NGF signaling.