The effect of carbonic anhydrase inhibitors and other drugs on sodium entry to cerebrospinal fluid.

Single cerebrospinal fluid (CSF) samples, taken 7 min after the i.v. administration of tracer 22Na+, provided data for calculation of rate constants for entry of Na+ into CSF from plasma. Four carbonic anhydrase (CA) inhibitors and certain other drugs were studied in terms of 1) ability to reduce the entry of Na+ into CSF and 2) level of drug in plasma. Dose-response curves were generated for the CA inhibitors. Complete CA inhibition in this system is defined by kin 0.017 to 0.019 min-1, a reduction of about 35% from the control kin for Na+. Acetazolamide, ethoxzolamide and methazolamide were fully inhibitory at 20 mg/kg. Significant decreases, approximately 19%, were caused by 2 mg/kg of acetazolamide or ethoxzolamide; methazolamide unaccountably was less effective at this dose. Benzolamide was relatively inactive, but gave full effect at 150 mg/kg. The diuretics furosemide and bumetanide and the steroid dexamethasone showed no activity against Na+ entry. In considering these responses, attention is given to drug affinity for CA and to properties affecting access of inhibitors to CSF-secreting sites. There is a well recognized correlation between the movement of Na+ from plasma into CSF and the secretion of CSF. These data may, therefore, be taken as indicators of the relative ability of the drugs to decrease CSF flow.