A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat spinal cord.
1. The effects of intravenous administration of two alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of single neurones to iontophoretically applied excitatory amino acids. The tests were performed on spinal neurones in alpha-chloralose anaesthetized, spinalized rats. 2. Both the quinoxaline, NBQX (2-16 mg kg-1) and the 2,3-benzodiazepine, GYKI 53655 (2-8 mg kg-1) dose-dependently decreased responses to AMPA. 3. Both compounds were short acting, with half-recovery times of 15 min for NBQX and 7 min for GYKI 53655. 4. The selectivity for responses to AMPA over those to N-methyl-D-aspartate (NMDA) was significantly poorer for systemic NBQX than for either systemic GYKI 53655 or iontophoretic NBQX, suggesting that systemic NBQX may be converted to a less selective metabolite. 5. GYKI 53655 is therefore likely to be a more valuable tool than NBQX for the study of AMPA receptor-mediated processes in vivo.
Chizh
B A
BA
Department of Physiology, School of Medical Sciences, University of Bristol.
Cumberbatch
M J
MJ
Headley
P M
PM
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D007275:Injections, Intravenous; D007478:Iontophoresis; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; C079692:GYKI 53655; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid