The
anticonvulsant activity of competitive 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F)-
quinoxaline (
NBQX) and noncompetitive 2,3-benzodiazepines and
tetrahydroisoquinolines (THIQs)
AMPA/
kainate receptor antagonists, was tested in different experimental seizure models and compared with
diazepam, a conventional
antiepileptic drug acting on GABAergic neurotransmission. In particular, the compounds were evaluated against audiogenic and maximal electroshock
seizures (MES) test and pentetrazol (PTZ)
seizures model, and all of them showed protective action. In addition,
NBQX, 2,3-benzodiazepines and THIQs, but not
diazepam, were also protective against clonic and
tonic seizures and lethality induced by
kainate,
AMPA and ATPA, but were ineffective against
NMDA-induced
seizures. Only 2,3-benzodiazepines and some THIQs were able to affect 4-aminopyridine- and mercaptopropionic-
acid-induced
seizures. The duration of
anticonvulsant action of 33 micromol/kg of some 2,3-benzodiazepines and THIQs was also investigated in DBA/2 mice, a strain genetically susceptible to audiogenic
seizures, and it was observed that the derivative
THIQ-10c, possessing an acetyl group at the N-2 and a
chlorine atom on the C-1 phenyl ring, showed higher
anticonvulsant activity and longer-lasting protective effects.