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.
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.
Lanier
W L
WL
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905.
Perkins
W J
WJ
Karlsson
B R
BR
Milde
J H
JH
Scheithauer
B W
BW
Shearman
G T
GT
Michenfelder
J D
JD
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*
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate