In nine hippocampally kindled rats (5 normal and 4 microcephalic) a comparative study of the
antiepileptic effects of
carbamazepine, and
AF-CX 921 [(E)-2-[(alpha-amino)-phenylmethylene]-
benzo-[b]-thiophene-3(2H)- one] and its metabolite
AF-CX 1325 [(E)-2-[(alpha-amino)-phenylmethylene]-
benzo-[b]-thiophene-3-(2H)- one-1-
oxide], were compared with placebo. The treatment effects were tested 1, 2, 3, 4, and 5 h after
drug administration, and the testings were executed twice for each treatment and animal. The following
biological parameters were evaluated and statistically analyzed: duration of first AD (AD1); frequency of occurrence of focal spiking (FS) which followed AD1; frequency of occurrence of second AD (AD2) which followed FS; duration of total EEG epileptic activity (AD1 + FS + AD2); frequency of occurrence of convulsive
seizures (CS); frequency of occurrence of
partial seizures (epileptic behavior, automatisms); and frequency of occurrence of a quiet state of the animal, indicating no behavioral kindling response. All three drugs had clear
antiepileptic effects on EEG epileptic activity and clinical
seizures in comparison with placebo. The strongest
antiepileptic effect was produced by
AF-CX 1325. It reduced AD1 duration to approximately 50% of that in the placebo treatment, and was most effective in reducing occurrence of FS to 20% and AD2 to 33% of that in the placebo. It was the only
drug that decreased AD2 duration, and total EEG epileptic activity was reduced to less than 50% of that in the placebo. These EEG results were paralleled by clinical effects.(ABSTRACT TRUNCATED AT 250 WORDS)