Effect of low-affinity NMDA receptor antagonists on electrical activity in mouse cortical slices

The objective of this study was to investigate the effects of three low-affinity NMDA receptor antagonists, MRZ 2/279 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane HCl), AR-R 15896AR ([+]-α-phenyl-2-pyridine-ethanamine diHCl) and dextromethorphan on epileptiform activity in vitro. Epileptiform discharges were elicited in DBA/2 mouse cortical slices by perfusion with Mg 2+-free artificial cerebrospinal fluid. MRZ 2/279, AR-R 15896AR and dextromethorphan all reversibly decreased the frequency of the discharges in a concentration-dependent manner. The IC 50's for MRZ 2/279, AR-R 15896AR and dextromethorphan were 5.2, 10.8 and 55.9 μM, respectively. These low-affinity NMDA receptor antagonists may be proved to be clinically effective with fewer adverse effects than drugs with high-affinity for the NMDA receptor-operated channel.