The effects of AMPA receptor antagonists on kindled seizures and on reflex epilepsy in rodents and primates.
Two potent glutamate antagonists, NBQX and GYKI 52466, that act selectively on non-NMDA receptors, have been tested for anticonvulsant activity in 3 models of reflex epilepsy (sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone rats and photically-induced myoclonus in Papio papio) and in amygdala kindled rats. Both compounds potently but transiently suppress reflexly-induced epileptic responses. GYKI 52466 also reduces behavioral seizures and afterdischarge duration in amygdala kindled rats, but with a lower potency than it suppresses reflex epilepsy. These data are similar to earlier results with antagonists acting selectively on NMDA receptors; they do not support a specific involvement of enhanced AMPA receptor sensitivity as a major factor in the expression of kindled seizures.
Meldrum
B S
BS
Department of Neurology, Institute of Psychiatry, London, UK.
Craggs
M D
MD
Dürmüller
N
N
Smith
S E
SE
Chapman
A G
AG
D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D004831:Epilepsies, Myoclonic / Q000503:physiopathology; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010215:Papio; D010775:Photic Stimulation; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000502:physiology; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines