A novel method for the assessment of the threshold for
clonic seizures induced by
excitatory amino acids based on continuous infusion of the
glutamate agonists [alpha-amino-3-hydroxy-5-terbutyl-4-isoxazolepropionate (ATPA),
kainate or
N-methyl-D-aspartate (
NMDA)] into the lateral brain ventricle of unrestrained mice is reported. Using this novel method of seizure threshold determination, it was found that systemically administered
diphenylhydantoin and
carbamazepine elevated the threshold for ATPA and had negligible effects on the threshold for
kainate and
NMDA.
Phenobarbital and
trimethadione elevated the threshold for all
excitatory amino acids tested, whereas
valproate elevated the threshold for ATPA and
kainate seizures.
Ethosuximide elevated the threshold for ATPA and
kainate and decreased the threshold for
NMDA seizures. The
quisqualate antagonists [2,3-dihydroxy-6-nitro-7-sulfamoyl-
benzo(F)quinoxaline and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-
benzodiazepine] elevated the threshold for ATPA and less so for
kainate seizures, whereas the
NMDA antagonist 3-((+-)2-carboxypiperazine-4-yl)-propyl-1-
phosphonate elevated the threshold for
NMDA seizures. 1-(4-Aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine in higher doses was also active against
NMDA seizures, whereas 3-((+-)2-carboxypiperazine-4-yl)-propyl-1-
phosphonate did so with
kainate seizures. Among seven different
convulsants,
pentylenetetrazol,
picrotoxin and the
beta-carboline methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate lowered the threshold for
seizures induced by
excitatory amino acids.
Pentylenetetrazol and
picrotoxin did so with
kainate seizures, whereas
methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate lowered ATPA thresholds.
Bicuculline, 3-mercaptopropionate,
strychnine and
pilocarpine were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)