Figure 1.
Low micromolar concentrations of memantine manifest relatively little effect on synaptic NMDAR-mediated currents.
A
, At 1 μm, memantine exerted a minimal effect on the NMDAR component of the EPSC. For comparison, nearly complete blockade by 1 μm MK-801 is shown.
B
, At 100 nm, MK-801 also nearly completely blocked synaptic NMDARs.
C
, After the inhibitory effect reached a plateau, 1 μm memantine blocked only 27.1 ± 1 3% of the NMDAR-mediated component of the EPSC, whereas equimolar MK-801 rendered virtually complete blockade (93.6 ± 0.5%). To reach a plateau with 100 nm MK-801, we performed prolonged recordings and still observed 91.6 ± 0.7% blockade of synaptic currents; 10 nm MK-801, although not reaching a plateau, also blocked nearly all of the EPSCNMDAR (data not shown).
D
, At 1 μm, memantine blockade of the NMDAR-mediated component of the EPSC reached a plateau within 100 s, whereas 1 μm MK-801 required ∼500 s. Electrical pulses to elicit EPSCs were delivered every 10 s. Values are mean ± SEM, measured at peak current (n = 28; *p < 0.0001 by t test).