The neuroprotective actions of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) in a rat focal ischaemia model

doi:10.1016/0006-8993(92)90924-X

Brain Research

Volume 580, Issues 1–2, 15 May 1992, Pages 35-43

https://doi.org/10.1016/0006-8993(92)90924-X Get rights and content

Abstract

The neuroprotective effects of NBQX, a selective antagonist for the AMPA/kainate subtype of excitatory amino acid receptors, were investigated in a rat focal ischaemia model, involving permanent occlusion of the left middle cerebral artery (MCA). NBQX (3, 10 or 30 mg/kg) was administered i.v. immediately after MCA occlusion and again 1 h later. The highest dose of NBQX (2 × 30mg/kg) gave significant protection against hemispheric (24%) and cortical (27%) ischaemic damage. The lower doses of NBQX (2 × 3or2 × 10mg/kg) were ineffective. No protection was seen against caudate damage for any of the doses of NBQX tested. NBQX has a t1/2 of 30 min, therefore, a second experiment was done in which a dose of 30 mg/kg was given as an i.v. bolus followed immediately by an infusion of 10 mg/kg/h for 4 h, dosing was started immediately after MCA occlusion. This dosing regimen resulted in a mean plasma level over the 4 h of 17 μg/ml, and significant protection against the volume of hemispheric (29%) and cortical (35%) ischaemic damage, which was slightly better than that achieved with two bolus doses of 30 mg/kg. Once again no protection was seen against caudate damage. We conclude that NBQX, an AMPA/kainate antagonist was neuroprotective in a focal ischaemia model in the rat.

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^*: Current address: Novo Nordisk A/S, CNS Division, Novo Nordisk Park, DK-2760 Malov, Denmark.

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The neuroprotective actions of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) in a rat focal ischaemia model

Abstract

Neuron

Brain Res.

Neuron

Nature

Science

Annu. Rev. Pharmacol. Toxicol.

Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats

Stroke

Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischaemia monitored by intracerebral microdialysis

J. Neurochem.

Infarct reduction by NMDA antagonists in a rat stroke model

Excitatory amino acid receptor antagonists: failure to prevent ischemic neuronal damage

J. Cereb. Blood Flow Metab.

Do NMDA antagonists protect against cerebral ischemia: are clinical trials warranted?

Cerebrovasc. Brain Metab. Rev.

The N-methyl-d-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats

J. Neurosci.

Focal cerebral ischaemia in the cat: pretreatment with a competitive NMDA receptor antagonist,d-CPPene

J. Cereb. Blood Flow Metab.

Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion

Stroke

Systemic administration of MK-801 protects against ischaemia-induced hippocampal neurodegeneration in the gerbil

J. Neurosci.

Neuroprotective actions of MK-801 in a rat global ischaemia model

J. Cereb. Blood Flow Metab.

Neuroprotective actions of MK-801 in a rat global ischaemia model

J. Cereb. Blood Flow Metab.

The neuroprotective action of Dizocilpine (MK-801) in the rat middle cerebral artery occlusion model of focal ischaemia

Br. J. Pharmacol.

The neuroprotective action of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) in a rat focal ischaemia model

The neuroprotective action of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) in a rat focal ischaemia model

J. Cereb. Blood Flow Metab.

Ischaemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments

J. Cereb. Blood Flow Metab.

Triphenyltetrazolium chloride (TTC) as a marker for ischaemic changes in rat brain following permanent middle cerebral artery occlusion

Neuropathol. Appl. Neurobiol.