title: 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.
abstract: 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 micrograms/kg i.v. over 5 min, followed by an infusion of 150 micrograms/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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905.
authors.forename: W L
authors.initials: WL
authors.lastname: Lanier
authors.forename: W J
authors.initials: WJ
authors.lastname: Perkins
authors.forename: B R
authors.initials: BR
authors.lastname: Karlsson
authors.forename: J H
authors.initials: JH
authors.lastname: Milde
authors.forename: B W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: G T
authors.initials: GT
authors.lastname: Shearman
authors.forename: J D
authors.initials: JD
authors.lastname: Michenfelder
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003986:Dibenzocycloheptenes / Q000097:blood / Q000627:therapeutic use*; D016291:Dizocilpine Maleate; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008254:Macaca nemestrina; D008297:Male; D010865:Pilot Projects; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*
chemical_list: D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate