Abstract
d- and l-enantiomers of the competitive NMDA antagonists CPP and CPP-ene, as well as the non-competitive NMDA antagonist MK-801, inhibited spontaneous activity occurring in slices of rat cerebral cortex exposed to Mg 2+-free medium. D-CPP-ene (SDZ EAA 494) was the most active competitive antagonist with a threshold concentration of 10 nM and an ED 50 of 39 nM. The inhibitory effects of all competitive antagonists were reversible, whereas reversibility following MK-801 (ED 50 = 33 nM) was incomplete and slow. D-CPP-ene was also the most potent competitive antagonist against NMDA-evoked depolarizations, having an apparent pA 2 value of 6.8; its action was specific to the NMDA type of excitatory amino acid receptor.
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