EFFECT OF BENZOLAMIDE ON CEREBROSPINAL FLUID FORMATION

¹ Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

Benzolamide is a powerful carbonic anhydrase inhibitor with very low lipid solubility and a high degree of ionization at physiologic pH. The effect of this inhibitor on cerebrospinal fluid (CSF) production and the distribution of the drug in blood, CSF and choroid plexus were studied in anesthetized cats. Intravenous injection of 1 mg/kg caused near maximal reduction (41%) in CSF formation At that dose about 0.3 gimM drug was found in CSF, while the choroid plexus was able to concentrate benzolamide in sufficient quantities to completely inhibit carbonic anhydrase. Further concentration of benzolamide in the choroid plexus was observed after higher i.v. doses. When the drug was perfused through the cerebral ventricles, a concentration of 0.3 µM was necessary for 25% reduction in CSF formation rates. When the removal of benzolamide from the CSF was studied, a small, saturable transport process, presumably located in the choroid plexus, was seen. Using low (0.3 µM) concentrations of benzolamide in the ventricular perfusate, the choroid plexus was able to concentrate the drug up to choroid plexus/perfusate ratios of about 30. These studies indicate that carbonic anhydrase in cat choroid plexus is very sensitive to inhibition by i.v. and intraventricular benzolamide. This is due to the access of drug to the enzyme site when presented from the blood or CSF side.

This article has been cited by other articles:

				T. H. Maren, C. W. Conroy, G. C. Wynns, and D. R. Godman Renal and Cerebrospinal Fluid Formation Pharmacology of a High Molecular Weight Carbonic Anhydrase Inhibitor J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 98 - 104. [Abstract] [Full Text]