THE EFFECT OF CARBONIC-ANHYDRASE INHIBITORS AND OTHER DRUGS ON SODIUM ENTRY TO CEREBROSPINAL-FLUID

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (1) , 51-56
Abstract
Single 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 [in rats]. Four carbonic anhydrase (CA) inhibitors and certain other drugs were studied in terms of ability to reduce the entry of Na+ into CSF and level of drug in plasma. Dose-response curves were generated for the CA inhibitors. Complete Ca inhibition in this system is defined by kin [rate constant for entry to CSF] 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, .apprx. 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 be taken as indicators of the relative ability of the drugs to decrease CSF flow.