Focal ischemic damage is reduced by CPP-ene studies in two animal models

Stroke. 1990 Nov;21(11 Suppl):III32-6.

Abstract

We have studied a new high-affinity competitive N-methyl-D-aspartate antagonist, D-CPP-ene (SDZ-EAA 494), in two models of focal cerebral ischemia. In the cat middle cerebral artery occlusion model (6 hours' survival), pretreatment with D-CPP-ene reduced infarct size by 64% (15 mg/kg dose) and 60% (4.5 mg/kg dose). There was no reduction in infarct size at a dose of 1.5 mg/kg. Treatment 1 hour after the occlusion reduced infarct size slightly, but not significantly. In a new model of subdural hematoma in the rat, the zone of cortical ischemic damage beneath the blood clot was reduced by 54% with D-CPP-ene pretreatment. Neuroprotective efficacy in a gyrencephalic species comparable to that of noncompetitive antagonists thus can be achieved with this agent. These experiments also indicate that competitive N-methyl-D-aspartate antagonists may be clinically useful after traumatic intracranial hematomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Cats
  • Constriction
  • Disease Models, Animal
  • Hematoma, Subdural
  • Male
  • Piperazines / therapeutic use*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • SDZ EAA 494