The
anticonvulsant properties of 1,4-benzodiazepines (BDZs), pyrazoloquinolones (CGS), 2-aryl-2,5-dihydropyridazino[4, 3-b]indol-3(3H)-ones (PIs) 1 1i 1d 1f 1e 1b 1c 1h, and 1a, the latter being inactive against audiogenic
seizures. Some PIs 1 and
abecarnil showed
anticonvulsant properties against
seizures induced by PTZ with a potency lower than that observed in audiogenic
seizures. The pharmacological actions of 1d, 1f, and 1i were significantly reduced by a treatment with
flumazenil (8.24 micromol/kg IP), suggesting a clear involvement of
benzodiazepine mechanisms in the
anticonvulsant activity of these compounds or their metabolites. The
anticonvulsant activity of 1d, 1f, and 1i was also evaluated against
seizures induced by two
beta-carbolines namely methyl-beta-carboline-3-carboxylate (
beta-CCM) and methyl-6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (
DMCM), in DBA/2 mice: they gave better protection against
seizures induced by
beta-CCM than the ones by
DMCM. The potency of various BDZs and PIs as inhibitors of specific [3H]
flumazenil binding to neuronal membranes, was also evaluated. The radioligand binding study, carried out on stable cell lines expressing definite combinations of
benzodiazepine receptor subunits, demonstrated that 1b, 1e, 1d, and 1h have preferential interaction with alpha(1), beta(3), gamma(2), receptor subtypes.