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Low Doses of NMDA Receptor Antagonists Synergistically Increase the Anticonvulsant Effect of the AMPA Receptor Antagonist NBQX in the Kindling Model of Epilepsy
Author(s) -
Löscher Wolfgang,
Rundfeldt Chris,
Hönack Dagmar
Publication year - 1993
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1993.tb00224.x
Subject(s) - nbqx , ampa receptor , nmda receptor , pharmacology , chemistry , glutamate receptor , antagonist , anticonvulsant , long term depression , excitatory amino acid antagonists , neuroscience , epilepsy , receptor , medicine , biology , biochemistry
Excitatory amino acid transmitters are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using N ‐methyl‐d‐aspartate (NMDA) receptors, although more recent evidence indicates potential roles for the a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors as well. In the present experiments in amygdala‐kindled rats, i.e. a model of partial epilepsy, competitive and uncompetitive NMDA antagonists exerted only weak anticonvulsant effects, whereas the AMPA antagonist 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoylbenzo(F)quinoxaline (NBQX) potently increased focal seizure threshold and inhibited seizure spread from the focus. These effects of NBQX were dramatically increased by pretreatment with low doses of NMDA antagonists, whereas adverse effects of NBQX were not potentiated. These data suggest that both non‐NMDA and NMDA receptors are critically involved in the kindled state, and that combinations of AMPA and NMDA receptor antagonists provide a new strategy for treatment of epileptic seizures.