In vitro neuroprotection against glutamate toxicity provided by novel non-competitive N-methyl-d-aspartate antagonists

Primary cultures of embryonic cortical cells were used to test the neuroprotective effect of two novel non-competitive N-methyl-D-aspartate antagonists against the neurotoxicity of glutamate. These two compounds, GK 11 and GK 222, are phencyclidine derivatives that contain asymetric carbon atoms. We have tested the neuroprotective effects of the racemates as well as those of the corresponding plus and minus enantiomers and have compared them with the reference drug dizocilpine (MK-801). We show here that the (-) enantiomers have a significantly better protective effect than the (+) enantiomers, but that the former are as efficient as the corresponding racemates. Qualitative analysis with different neuronal and glial markers does not reveal any difference in the population of protected cells among the different molecules tested.