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Effects of Carbamazepine, AF‐CX 921, and AF‐CX 1325 on Epileptic Discharges and Seizures in Hippocampally Kindled Rats

Summary: 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‐[(α‐amino)‐phenylmethylene]‐benzo‐[b]‐thiophene‐3(2H)‐one] and its metabolite AF‐CX 1325 [(E)‐2‐[(α‐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: (1) duration of first AD (AD1); (2) frequency of occurrence of focal spiking (FS) which followed AD1; (3) frequency of occurrence of second AD (AD2) which followed FS; (4) duration of total EEG epileptic activity (AD1 + FS + AD2); (5) frequency of occurrence of convulsive seizures (CS); (6) frequency of occurrence of partial seizures (epileptic behavior, automatisms); (7) 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 ˜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 <50% of that in the placebo. These EEG results were parelled by clinical effects. Control of CS (73% in the placebo treatment) was best expressed by AF‐CX 1325 (reduced to 18%), followed by AF‐CX 921 (reduced to 21%) and CBZ (reduced to 38%).