Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia.
Ischemia may increase synaptic concentrations of glutamate, which may cause neuronal damage. Drugs that antagonize glutamate's effects may reduce this type of damage. MK-801, an N-methyl-D-aspartate receptor antagonist that readily enters the central nervous system, was evaluated in two focal central nervous system ischemia models: a multiple cerebral embolic model and a rabbit spinal cord ischemia model. When animals were treated five minutes after the onset of injury, MK-801 was effective in reducing ischemic damage in both models. In the multiple cerebral embolic model, the average dose of microspheres trapped in the brain increased from 344.8 +/- 51.4 micrograms (n = 29) in controls to 534 +/- 41.4 micrograms (n = 17) in the MK-801-treated group. Similarly, in the rabbit spinal cord ischemia model, the average ischemia duration increased from 28.9 +/- 1.7 minutes (n = 52) in controls to 50.6 +/- 3.9 minutes (n = 12) in the MK-801-treated group. These results suggest that this glutamate antagonist should be useful for the treatment of stroke.
Kochhar
A
A
Department of Neurology, Veterans Administration Medical Center, San Diego.
Zivin
J A
JA
Lyden
P D
PD
Mazzarella
V
V
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply*
D003986:Dibenzocycloheptenes; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate