Inhibition of kindling-induced generalized seizures by aminooxyacetic acid

The anticonvulsant effect of aminooxyacetic acid (AOAA) was examined on a model of experimental epilepsy (kindling) induced by daily appropriate amygdaloid stimulation in the rat. Doses from 5 to 30 mg/kg were intraperitoneally administered in fully kindled animals 3--4 h before triggering a seizure. At low doses (less than 15 mg/kg) AOAA had no effect whereas at higher doses (greater than 15 mg/kg) it reduced the severity of the generalized kindled seizures in over half the cases, and even sometimes completely blocked them. The inhibition of epileptic activity by AOAA is in accordance with the hypothesis that an increase in GABA level is associated with a reduction of epileptic sensitivity. An unexpected lengthening of the afterdischarge duration was also observed in about 20% of the cases, independently of the amount administered. This fact is discussed in regard to the complex action of AOAA on gamma-aminobutyric acid related enzymes. Finally, since the afterdischarge threshold was shown to be unaffected by the drug, it is suggested that it may act on the afterdischarge propagation rather than at the focal amygdaloid level.