THE ANTICONVULSANT POTENCY OF INHIBITORS OF CARBONIC ANHYDRASE IN YOUNG AND ADULT RATS AND MICE

¹ Department of Experimental Pharmacology, Lederle Laboratories, Pearl River, New York

Adult rats, in contrast with young rats, showed decreases in susceptibility to electroshock and in severity of seizures at a stimulus intensity of 150 mA. These decreases apparently account for the increased anticonvulsant potency of methazolamide and acetazolamide in mature animals. Increasing the stimulus intensity to 500 mA partially restored the severity of seizures and fully restored the incidence of seizures and the anticonvulsant potency of methazolamide to that seen in the younger animals (acetazolamide was not studied). In young rats, seizure severity was increased and the anticonvulsant potency of the carbonic anhydrase inhibitors was decreased at the stimulus intensity of 500 mA, showing that both seizure incidence and severity are involved in the measurement of anticonvulsant potency. In mice, the decrease in the anticonvulsant potency of the carbonic anhydrase inhibitors with age could not be attributed to a change in the susceptibility to electroshock. Severity of seizures was not measured. The data also show that changes in inhibitor and enzyme concentrations in brain and red cells are not involved. The anticonvulsant potency of CO₂ was also found to decrease with age in mice, providing further evidence that disequilibrium of the CO₂ buffer system is involved in the anticonvulsant action of inhibitors of carbonic anhydrase.