NATURE OF THE INHIBITION OF CARBONIC ANHYDRASE BY ACETAZOLAMIDE AND BENZTHIAZIDE

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

The inhibition of the carbonic anhydrasecatalyzed hydration of carbon dioxide by acetazolamide or by benzthiazide, after equilibration of drug with enzyme at 5°C and pH 8.0 in the absence of substrate, obeys noncompetitive kinetics. Acetazolamide rapidly comes to equilibrium with the enzyme under these conditions, with a small increase in potency. Benzthiazide requires a longer period for equilibrium to be established, during which time a marked increase in extent of inhibition occurs. This increase is greatly diminished when substrate is present. The K_i of acetazolamide is, under these conditions, 8.5 x 10^-9 M; that of benzthiazide is 1.4 x 10^-8 M. The combination of acetazolamide with the enzyme is freely reversible. Benzthiazide, however, does not exhibit the classical behavior of either a completely reversible or a completely irreversible inhibitor.