Arcaine sulfate is a competitive inhibitor of the NMDA receptor and also an inhibitor of the enzyme NO synthase. It has an effective concentration of 50-500 μM and an IC50 of 61μM at -60mV. Arcaine binds to the polyamine recognition site of the NMDA receptor complex and blocks the receptor in a concentration and voltage dependent manner. In positive membrane potentials Arcaine does not produce a blocking effect. In the presence of 100 μM Arcaine (at -60 mV), NMDA amplitude whole cell currents are reduced by 67% and by 69% in single channel recordings. The inhibitory effect of Arcaine is rapid in onset and recovery (<100ms in both cases) and occurs when the receptor is in its open state. Arcaine does not inhibit other glutamate receptors such as AMPA and Kainate and does not affect GABA elicited currents. When applied with dizocilpine, another open state NMDA blocker, Arcaine prevents dizocilpine from producing a long lasting blockage of the receptor thus indicating the existence of a competitive interaction between the two substances
