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Karlsson, Bente R.

Mayo Clinic

University of Oslo

Citations 1

The Effects of Dizocilpine Maleate (MK-801), an Antagonist of the N -Methyl-D-Aspartate Receptor, on Neurologic Recovery and Histopathology following Complete Cerebral Ischemia in Primates
Lanier, William L. , Perkins, William J., Karlsson, Bente R., Milde, James H., Scheithauer, Bernd W., Shearman, Gary T., Michenfelder, John D.

Journal of Cerebral Blood Flow & Metabolism | April 8, 2011 | Volume: 10 | Issue: 2 | Pages: 252-261

10.1038/jcbfm.1990.42 Get It

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 μg/kg i.v. over 5 min, followed by an infusion of 150 μg/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups ( p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.