Arcaine sulfate

Glutamate is the main excitatory neurotransmitter in the CNS and is also involved in a variety of pathological conditions including epilepsy. Glutamate binds to the ionotropic NMDA receptor to relay its excitatory signal.

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 61 μM at -60 mV. Arcaine binds to the polyamine recognition site of the NMDA receptor complex and blocks the receptor in a concentration- and voltage-dependent manner. At 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 (<100 ms 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 blockade of the receptor thus indicating the existence of a competitive interaction between the two substances¹.