DEXTROMETHORPHAN AND PHENCYCLIDINE RECEPTOR LIGANDS - DIFFERENTIAL-EFFECTS ON K+-EVOKED AND NMDA-EVOKED INCREASES IN CYTOSOLIC FREE CA2+ CONCENTRATION

The ability of dextromethorphan (DXM) and phencyclidine (PCP) receptor ligands to attenuate increases in cytosolic free Ca2+ concentration ([Ca2+]i) evoked by N-methyl-D-aspartate (NMDA) and high extracellular [K+] was examined using the fluorescent dye Fura 2 in cultured rat hippocampal pyramidal neurons. The DXM receptor ligand caramiphen (40-mu-M) reduced K+-evoked rises in [Ca2+]i to a greater extent than NMDA-evoked rises; the reverse was true for the PCP receptor ligands ketamine (10-40-mu-M) and dextrorphan (10-mu-M). DXM itself, which has affinity for both DXM and PCP receptors, reduced both K+- and NMDA-evoked increases in [Ca2+]i in a concentration-dependent manner. The results suggest that DXM receptor ligands may at least in part exert their known anticonvulsant and neuroprotective effects by reducing Ca2+ influx through voltage-activated Ca2+ channels.