Correlation between effects of acute acetazolamide administration to mice on electroshock seizure threshold and maximal electroshock seizure pattern, and on carbonic anhydrase activity in subcellular fractions of brain.
The relationships between inhibition of carbonic anhydrase (CA) activity in cytoplasmic, microsomal, and myelin subcellular fractions obtained from cerebral cortex, subcortex, and cerebellum and electroshock seizure threshold (EST) and modification of the extension/flexion (E/F) ratio following maximal electroshock seizures (MES) were ascertained in Swiss-Webster mice given 40 and 200 mg/kg acetazolamide. The parameters were determined at 1, 4, and 24 h after administration of acetazolamide. The results showed that changes in the E/F ratio induced by acetazolamide correlated linearly (r = 0.90) with changes in CA activity in the cytoplasm of the subcortex. However, there was an inverse power function correlation (r = 0.92) between EST and CA activity in the myelin fraction of the cerebral cortex. The time course of acetazolamide inhibition of CA activity in these two fractions also paralleled the time course of its effects on EST and E/F ratio. Thus, acetazolamide decreases susceptibility to seizures (raises EST) by inhibiting myelin CA and prevents spread of seizure activity by inhibiting CA in the cytoplasm of glial cells. The CO2 that accumulates as a result of CA inhibition in these two fractions causes profound changes in brain function.
D000086:Acetazolamide / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004056:Differential Threshold; D004597:Electroshock; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D013347:Subcellular Fractions / Q000378:metabolism
D002256:Carbonic Anhydrases; D000086:Acetazolamide