title: Evidence that GYKI 52466, a novel non-NMDA antagonist enhances the decay of kainate-induced current in cultured chicken cortical neurons.
abstract: The effect of a novel non-competitive non-NMDA glutamate receptor antagonist, GYKI 52466 was studied on the glutamate agonist-induced currents in one month old cultured embryonal chicken brain neurons by a whole cell patch-clamp technique. AMPA, applied in different concentrations (30-1000 microM) did not evoke any current. Kainate evoked an increase of steady-state current (KA-current). NMDA induced a current with 5-10 times higher peak amplitude than KA, but GYKI 52466 failed to affect this current. It reduced the amplitude of KA-current in a concentration-dependent (1-100 microM) manner, and produced a slow decay of it. The IC50 value of GYKI 52466 against 100 microM KA was 20.4 +/- 6.4 microM with a Hill coefficient of 1.12. The inhibition of KA-currents was voltage-dependent with greater inhibition between -110 to -40 mV than between -30 and +60 mV. In order to compare the effect of GYKI 52466 with a well-known competitive non-NMDA antagonist, we also studied the effect of the quinoxalinedione CNQX. When GYKI 52466 and CNQX were applied together there was only a small additive effect. Our results with GYKI 52466 on glutamate agonist-induced currents in embryonic chicken cortical neurons are similar to those observed in rat hippocampal neurons.
authors.affiliation: Department of Pharmacology, Hungarian Academy of Sciences, Budapest.
authors.forename: O
authors.initials: O
authors.lastname: Osipenko
authors.forename: A
authors.initials: A
authors.lastname: Mike
authors.forename: A
authors.initials: A
authors.lastname: Gyevai
authors.forename: E S
authors.initials: ES
authors.lastname: Vizi
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D009498:Neurotoxins; D011810:Quinoxalines; C061950:GYKI 52466; D001569:Benzodiazepines; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid