Efficacy of D-CPPene, a competitive N-methyl-D-aspartate antagonist in focal cerebral ischemia in the rat.
The effect of a novel and potent competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPPene) upon ischemic brain damage has been examined in a rat model of focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). The animals were sacrificed 24 h after MCA occlusion and the amount of ischemic brain damage was assessed at 8 predetermined coronal planes. Pretreatment with D-CPPene (1.5, 4.5 or 15 mg/kg, i.v.), initiated 15 min prior to MCA occlusion (followed by constant infusion at 1, 3 or 10 mg/kg/h), produced dose-dependent reductions in the volumes of infarction; the dose of 4.5 mg/kg being the most effective (reduced by 37%; P < 0.01). These results indicate that systemic administration of the competitive NMDA antagonist D-CPPene has neuroprotective effects in a model of focal cerebral ischemia and define the dose dependency of its neuroprotective effects.
Park
C K
CK
Department of Neurosurgery, Catholic University Medical College, Seoul, South Korea.
McCulloch
J
J
Kang
J K
JK
Choi
C R
CR
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494