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

Neurosci Lett. 1990 Jun 8;113(3):315-21. doi: 10.1016/0304-3940(90)90604-8.

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 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.

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Dibenzocycloheptenes / pharmacology*
  • Dizocilpine Maleate
  • Evoked Potentials / drug effects
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / antagonists & inhibitors
  • Receptors, Neurotransmitter / physiology*

Substances

  • Dibenzocycloheptenes
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • SDZ EAA 494
  • Dizocilpine Maleate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid