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).[214] Creatine appears to modulate the polyamine binding site of the NMDA receptor, as it is abolished by arcaine and potentiated by spermidine.[215] This binding site is known to modify NMDA receptor affinity.[216][217]
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