Focal ischemic damage is reduced by CPP-ene studies in two animal models.
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.
Bullock
R
R
Department of Neurosurgery, University of Glasgow, Scotland.
McCulloch
J
J
Graham
D I
DI
Lowe
D
D
Chen
M H
MH
Teasdale
G M
GM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002415:Cats; D003250:Constriction; D004195:Disease Models, Animal; D006408:Hematoma, Subdural; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494