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Drug Discovery and Evaluation pp 168–182Cite as

Renal activity

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Abstract

Acetazolamide (Diamox®) was one of the first synthetic non-mercurial diuretics. The mode of action was found to be inhibition of carbonic anhydrase. Carbonic anhydrase is a zinc-containing enzyme that catalyzes the reversible hydration (or hydroxylation) of CO2 to form H2CO3 which dissociates non-enzymatically into HCO3 − and H+. At least three isoenzymes, designated as I, II and II or A, B and C, are known to exist. The chemistry, physiology and pharmacology of carbonic anhydrase has been extensively reviewed by Maren (1967). In spite of the fact that newer diuretics are based on other modes of action, the test for inhibition of carbonic anhydrase should be performed for evaluation of a new compound. Moreover, the specific use of carbonic anhydrase inhibitors as antiglaucoma drugs has been described (Friedland and Maren 1984, Caprioli 1985). The mechanism by which carbonic anhydrase inhibitors lower intraocular pressure is through a reduction in aqueous humor formation, by affecting electrolyte and water balance in the nonpigmented ciliary epithelium (Friedland and Maren 1984, Caprioli 1985). Although many methods to measure carbonic anhydrase activity have been developed (Philpot and Philpot 1936), the micro method described by Maren (1960) is relatively simple, sensitive and reliable. The enzyme source are red cells, a rich source of the same isoenzymes found in the eye (Maren 1967, Armstrong et al 1966, Wistrand et al 1986, Wistrand and Knuutila 1980).

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  1. Johann Wolfgang Goethe Universität Frankfurt, D-60569, Frankfurt am Main, Germany

    Prof. Dr. med. Dr.s.c. H. Gerhard Vogel

  2. Philipps Universität Marburg, D-35037, Marburg, Germany

    Prof. Dr. med. Dr.s.c. H. Gerhard Vogel

  3. Department of Pharmacology Jefferson Medical College, Thomas Jefferson University, 19107, Philadelphia, PA, USA

    Professor Dr. Wolfgang H. Vogel

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  1. Johann Wolfgang Goethe Universität Frankfurt, D-60569, Frankfurt am Main, Germany

    H. Gerhard Vogel

  2. Philipps Universität Marburg, D-35037, Marburg, Germany

    H. Gerhard Vogel

  3. Department of Pharmacology Jefferson Medical College, Thomas Jefferson University, 19107, Philadelphia, PA, USA

    Wolfgang H. Vogel

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Vogel, H.G., Vogel, W.H. (1997). Renal activity. In: Vogel, H.G., Vogel, W.H. (eds) Drug Discovery and Evaluation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03333-3_3

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