Anticonvulsant activity of AMPA/kainate antagonists: comparison of GYKI 52466 and NBOX in maximal electroshock and chemoconvulsant seizure models.
The anticonvulsant activities of a noncompetitive (GYKI 52466) and a competitive (NBQX) AMPA/kainate antagonist were compared in the maximal electroshock (MES) seizure test and various chemoconvulsant models. Both antagonists were protective in the MES and pentylenetetrazol tests. GYKI 52466 was also protective against seizures and lethality induced by 4-aminopyridine, kainate and AMPA, but not by NMDA, whereas NBQX was ineffective in these chemoconvulsant tests. Both GYKI 52466 and NBQX produced motor impairment at doses similar to those that were protective in the MES test. Under some circumstances, noncompetitive AMPA/kainate antagonists could offer advantages over competitive antagonists in seizure therapy. However, neurological toxicity is an obstacle to the potential clinical use of both classes of agents.
Yamaguchi
S
S
Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 29892.
Donevan
S D
SD
Rogawski
M A
MA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006614:Hindlimb / Q000502:physiology; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011810:Quinoxalines / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
D015761:4-Aminopyridine; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001569:Benzodiazepines; D007608:Kainic Acid; D010433:Pentylenetetrazole; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline