Seizure Patterns in Young Animals. Significance of Brain Carbonic Anhydrase. II.

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Abstract
The effect of acetazolamide on electroshock seizure patterns of young rats has been observed in parallel with estimations of the degree of inhibition of brain carbonic anhydrase activity. The ED50 for maximal tonic and for clonic seizures was 1 mg/kg and 86 mg/kg and the percentage inhibition of the enzyme was 86 and 99.4, respectively. Minor hyperkinetic seizure patterns were refractory to acetazolamide, 1 g/kg, despite the inhibition of enzyme by 99.98%. The inhibition of the catalyzed reaction is not proportional to the inhibition of the enzyme; the corresponding values calculated from percent enzyme inhibition observed and data of H. W. Davenport, were 5, 38, and 83%. The reciprocals of these values, or the functional activity of the enzyme in acetazolamide-treated animals, were of a similar order of magnitude to the levels of brain enzyme activity which correlate with development of susceptibility to tonic, clonic, and hyper-kinetic seizure patterns. A low level of functional activity of carbonic anhydrase in the brain may be sufficient for the induction of minor hyperkinetic seizures while a relatively high degree of activity may be required for the propagation of a generalized discharge and the induction of a major tonic seizure.