Abstract
The selective alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) and the selective N-methyl-D-aspartate (NMDA) receptor antagonists MK 801 and ifenprodil were administered to Mongolian gerbils following a 5 min period of bilateral carotid artery occlusion. NBQX when given 4, 6 or 24 h after ischaemia gave a reduced loss of hippocampal CA1 neurones compared to control animals receiving vehicle only. Dizocilipine (MK 801) (1-10 mg/kg i.p.) and ifenprodil (a total of 45 mg/kg i.p.) gave no protection. The peak levels of NBQX obtained in the cerebrospinal fluid of gerbils receiving the neuroprotective dose (3 x 30 mg/kg i.p.) was 1 microM. In gerbil cortex slices, this concentration had no effect on NMDA-evoked depolarization, but had a moderate effect on kainate and gave a total blockade of AMPA depolarizations. It is concluded that antagonists of non-NMDA glutamate receptor subtypes, possibly AMPA, may be a useful therapeutic approach for cerebral ischaemia-related brain damage following global ischaemia.
MeSH terms
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Animals
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Cerebral Cortex / drug effects*
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Cerebral Cortex / metabolism
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Dizocilpine Maleate / administration & dosage
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Dizocilpine Maleate / cerebrospinal fluid
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Dizocilpine Maleate / pharmacology
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Excitatory Amino Acid Antagonists*
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Female
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Gerbillinae
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Hippocampus / cytology
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Hippocampus / drug effects*
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Ibotenic Acid / analogs & derivatives
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Ibotenic Acid / metabolism
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Ischemic Attack, Transient / drug therapy*
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Ischemic Attack, Transient / metabolism
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Ischemic Attack, Transient / pathology
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Kinetics
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Male
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Neurons / drug effects
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Piperidines / administration & dosage
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Piperidines / cerebrospinal fluid
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Piperidines / pharmacology
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Quinoxalines / administration & dosage
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Quinoxalines / cerebrospinal fluid
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Quinoxalines / pharmacology*
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Receptors, AMPA
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Receptors, Glutamate / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Substances
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Excitatory Amino Acid Antagonists
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Piperidines
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Quinoxalines
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Receptors, AMPA
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Receptors, Glutamate
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Receptors, N-Methyl-D-Aspartate
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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Ibotenic Acid
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Dizocilpine Maleate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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ifenprodil