Synergy between diazepam and NBQX in preventing neuronal death caused by non-NMDA agonists.
The non-N-methyl-D-aspartate (NMDA) glutamate receptor agonists kainate and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), when injected into the rat dorsal hippocampus, cause neuronal death directly by activating non-NMDA receptors and as a consequence of initiating seizure activity. Co-injection of the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 12.5-95 nmol) was partially effective in preventing up to about 60% of the direct excitotoxicity. On the other hand, diazepam (6 x 5 mg kg-1, i.p.) had only a minor protective effect against the direct neuronal damage, but was effective in preventing almost all the extra-hippocampal loss of neurones caused by seizure activity. The combination of intracerebral NBQX and systemic diazepam reduced the toxicity of kainate or AMPA to a greater extent than that found in the presence of either protectant alone. At optimum doses the neuronal cytotoxicity caused by non-NMDA agonists in the hippocampus was completely prevented.
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; D003975:Diazepam / Q000494:pharmacology*; D004357:Drug Synergism; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; 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; D003975:Diazepam; D007608:Kainic Acid