The pharmacology of SDZ EAA 494, a competitive NMDA antagonist

Neurochem Int. 1994 Dec;25(6):583-600. doi: 10.1016/0197-0186(94)90157-0.


SDZ EAA 494 (D-CPPene) was characterized as a competitive NMDA antagonist, having a pA2 value against NMDA depolarizations in frog spinal cord and rat neocortex of 6.7-6.8 and a pKi of 7.5 in a [3H]CGP39653 binding assay, with no action on other receptors or amine reuptake. The compound was orally active in rodent maximal electroshock models with an ED50 of around 16 mg/kg, was protective in rats even 24 hours after oral application and had an oral therapeutic index of around 8. Muscle relaxation, ataxia, flattened body posture and reduced acquisition of a passive avoidance task, suggesting potential effects on memory formation, occurred at supra-anticonvulsant doses in rodents, with PCP-like stimulatory effects produced only by high i.p. doses or constant i.v. infusions. This favourable profile is discussed in relation to the negative outcome of a recent trial of the compound in patients with intractable epilepsy. The conclusion is drawn that standard models for screening new anticonvulsants are inappropriate to seeking drugs active in patients with a protracted convulsive history. The anti-ischaemic action of SDZ EAA 494 encourages further testing in brain trauma, in which the anticonvulsant action of the compound may be an added benefit.

MeSH terms

  • Animals
  • Binding Sites
  • Cats
  • Corpus Striatum / drug effects
  • Dose-Response Relationship, Drug
  • Electroshock
  • Kynurenic Acid
  • Mice
  • N-Methylaspartate / antagonists & inhibitors*
  • Nomifensine / pharmacology
  • Piperazines / antagonists & inhibitors
  • Piperazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium
  • Spinal Cord / drug effects


  • Piperazines
  • SDZ EAA 494
  • Nomifensine
  • N-Methylaspartate
  • Sodium
  • Kynurenic Acid