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

BP Vogh and AS Doyle

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.

Volume 217, Issue 1, pp. 51-56, 04/01/1981
Copyright © 1981 by American Society for Pharmacology and Experimental Therapeutics