THE PROLONGED ANTICONVULSANT ACTION OF METHAZOLAMIDE IN ACIDOTIC MICE: THE ROLE OF CARBONIC ANHYDRASE

¹ Experimental Therapeutics Research Section, Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York

The anticonvulsant action of methazolamide in mice made acidotic by the administration of ammonium chloride persists during the period of the decline of inhibitor concentrations in brain and plasma; no correlation between these phenomena could be established. The concentration and persistence of inhibitor in red cells was well correlated with the persistence of the anticonvulsant action of methazolamide in acidotic mice; a causal relationship appears to be unlikely. There were no differences of any importance between the concentrations and the persistences of inhibitor in the brains, in the plasmas, or in the red cells of normal and acidotic mice. The latter showed a trend towards slightly greater concentrations in the brains and in the plasmas at certain times; these differences, if real, are probably of no biological importance.

Compared with normal mice, metabolic acidosis had no effect on the carbonic anhydrase activity of the brains of mice sacrificed at times corresponding to the period of the persistent anticonvulsant effect of methazolamide in other groups of acidotic mice. These data carry the reservation that activities were measured at the same pH in vitro, a condition that might not prevail in vivo.

The results of this study provide evidence that carbonic anhydrase in brain is not directly involved in the persistence of the anticonvulsant action of methazolamide in mice in metabolic acidosis.