Differences in antiepileptic drug efficacy in hippocampally kindled normal and microcephalic rats.
The difference in antiepileptic drug efficacy was investigated in two groups of animals: 5 normal and 4 microcephalic rats. The latter were produced by a single i.p. injection of 30 mg/kg methylazoxymethanol acetate in the mother on the 15th day of gestation. Hippocampal kindling was performed to a seizure criterion in all animals followed by testing of the antiepileptic drugs vs placebo. Besides carbamazepine (CBZ), two new anticonvulsants were tested: (E)-2-[(alpha-amino)phenylmethylene]-benzo-[b]-thiophene-3(2H)-one (AF-CX 921) and its metabolite (E)-2-[alpha-amino)phenylmethylene]-benzo-[b]-thiophene-3(2H)-one- 1- oxide (AF-CX 1325). Frequency of occurrence and duration of afterdischarges and seizures were statistically examined. The duration of early afterdischarges (AD1) tended to be shorter in microcephalic than in normal animals in control and placebo periods. In contrast, during treatment with the antiepileptic drugs, AD1 durations were longer in microcephalic than in normal animals. This suggests that the drugs inhibited AD1 to a lesser extent in the microcephalics. Two other characteristics of EEG epileptic activity, focal spiking (FS) and late afterdischarges (AD2) also varied in the two groups. Both were significantly lower in occurrence in the microcephalic rats independent of treatment. Three types of behavioral manifestations were also examined: convulsive seizures (CS), epileptic behavior (EB) and quiet states (Q). The two groups of animals responded differently to the drugs with respect to Q and CS. In the microcephalics, AFCX 1325 and AFCX 921 were superior to CBZ, which in turn, was superior to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D006624:Hippocampus; D007696:Kindling, Neurologic; D008831:Microcephaly / Q000150:complications*; D051381:Rats; D013876:Thiophenes / Q000627:therapeutic use
D000927:Anticonvulsants; D013876:Thiophenes; D002220:Carbamazepine; C039255:AF-CX 921XX; C048840:AF-CX 1325