Suppression by memantine and amantadine of synaptic excitation intrastriatally evoked in rat neostriatal slices.

The competitive N-methyl-D-aspartate (NMDA) receptor antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) and D(-)-2-amino-5-phosphonovaleric acid (APV), and the non-competitive NMDA antagonists, memantine and amantadine, which are used in the treatment of Parkinson's disease, were tested for their effects on intrastriatally evoked excitatory postsynaptic potentials (EPSPs) in rat neostriatal slices. Fast, non-NMDA receptor mediated synaptic excitation was not affected by any of the NMDA receptor antagonists. The NMDA component of the EPSPs was more prominent following reduction of the non-NMDA component of the EPSP by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM). Memantine (30 microM) and amantadine (100 microM) had similar effects in reducing the NMDA component, but were not as effective as CGP 37849 (1-5 microM) or APV (10 microM). The data are compatible with a possible locus of action of memantine and amantadine in the neostriatum.