Creatine has been noted to increase the amplitude (0.5-5mM) and frequency (25mM only) of NMDA receptors, although concentrations of 0.5-25mM also reduced signaling intensity. This was credited to creatine causing an increase in ligand binding of glutamate with an EC50 of 67µM and maximal activity at 1mM creatine (158±16% of baseline). Creatine appears to modulate the polyamine binding site of the NMDA receptor, as it is abolished by arcaine and potentiated by spermidine. This binding site is known to modify NMDA receptor affinity.
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