NBQX prevents contralateral but not ipsilateral seizure-induced cytotoxicity of kainate but not AMPA-reversal at high doses of NBQX.
The non-N-methyl-D-aspartate (NMDA) glutamate agonists are potent convulsants, and cause neuronal loss in many regions of the limbic system in the brain. Kainate or L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX) were concomitantly injected unilaterally into the rat dorsal hippocampus. Kainate with low doses of NBQX (12.5-25 nmol) almost completely prevented damage to the contralateral but not ipsilateral limbic areas (distal toxicity). In most animals, damage was still found in the contralateral midline thalamic nuclei. In contrast, high doses of NBQX (95-190 nmol) gave no protection to either side. AMPA showed a trend for a reduction in limbic damage to both sides with increasing dose of NBQX. At the highest doses, NBQX prevented damage to both sides.
Lees
G J
GJ
Department of Psychiatry and Behavioural Science, School of Medicine, University of Auckland, New Zealand.
Leong
W
W
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000188:drug therapy* / Q000473:pathology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid