D-CPP-ene (SDZ EAA 494), a potent and competitive N-methyl-D-aspartate (NMDA) antagonist: effect on spontaneous activity and NMDA-induced depolarizations in the rat neocortical slice preparation, compared with other CPP derivatives and MK-801.
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 Mg2(+)-free medium. D-CPP-ene (SDZ EAA 494) was the most active competitive antagonist with a threshold concentration of 10 nM and an ED50 of 39 nM. The inhibitory effects of all competitive antagonists were reversible, whereas reversibility following MK-801 (ED50 = 33 nM) was incomplete and slow. D-CPP-ene was also the most potent competitive antagonist against NMDA-evoked depolarizations, having an apparent pA2 value of 6.8; its action was specific to the NMDA type of excitatory amino acid receptor.
Lowe
D A
DA
Sandoz Research Institute Bern, Switzerland.
Neijt
H C
HC
Aebischer
B
B
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D005071:Evoked Potentials / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D003986:Dibenzocycloheptenes; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C065286:SDZ EAA 494; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid