[Skip to Content]
[Skip to Content Landing]
Article
August 1966

Site of Action of Ethacrynic Acid

Author Affiliations
LITTLE ROCK, ARK
From the Department of Medicine, University of Arkansas Medical Center, Little Rock, Ark.
Arch Intern Med. 1966;118(2):117-122. doi:10.1001/archinte.1966.00290140021005
Abstract

ETHACRYNIC acid (MK-595), an unsaturated ketone derivative of phenoxyacetic acid, was reported to be an effective diuretic in experimental animals in 1962.1,2 Subsequent reports 3-6 have confirmed its diuretic activity in man. The drug has attracted the attention of clinicians because of its potent therapeutic effect in edematous states refractory to conventional diuretic therapy. Studies, during antidiuresis by Goldberg et al7 and during water diuresis by Earley and Friedler,8 suggested that the drug's primary action in the kidney was inhibition of sodium transport in the ascending limb of Henle's loop. Activity at this site is unique among all other diuretics, with the possible exception of furosemide.9 Although the effect of ethacrynic acid on urine concentration and dilution are consistent with a block in sodium reabsorption at this segment of the nephron, both Goldberg and associates and Earley and Friedler indicated that it might have an additional effect at another site.

References
1.
Baer, J.E., et al:  New Class of Diuretic-Saluretic Agents: The α β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids ,  Pharmacologist 4:158 ( (Fall) ) 1962.
2.
Schultz, E.M., et al:  α, β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids: A New Class of Diuretics ;  J Med Pharm Chem 5:660-662 ( (May) ) 1962.Crossref
3.
Foltz, E.L.:  Preliminary Clinical Observations With Aryloxyacetic Acid Diuretic ,  Fed Proc 22:598 ( (March-April) ) 1963.
4.
Melvin, K.E.W.; Farrelly, R.O.; and North, J.D.K.:  Ethacrynic Acid: A New Oral Diuretic ,  Brit Med J 1:1521-1524 ( (June 8) ) 1963.Crossref
5.
Daley, D., and Evans, B.:  Diuretic Action of Ethacrynic Acid in Congestive Heart Failure ,  Brit Med J 2:1169-1171 ( (Nov 9) ) 1963.Crossref
6.
Cannon, P.J.; Ames, R.P.; and Laragh, J.H.:  Methylenebutyryl Phenoxyacetic Acid: Novel and Potent Natriuretic and Diuretic Agent ,  JAMA 185: 854-863 ( (Sept 14) ) 1963.Crossref
7.
Goldberg, M., et al:  Effects of Ethacrynic Acid (a New Saluretic Agent) on Renal Diluting and Concentrating Mechanisms: Evidence for Site of Action in the Loop of Henle ,  J Clin Invest 43:201-216 ( (Feb) ) 1964.Crossref
8.
Earley, L.E., and Friedler, R.M.:  Renal Tubular Effects of Ethacrynic Acid ,  J Clin Invest 43:1495-1506 ( (July) ) 1964.Crossref
9.
Suki, W.; Rector, F.C., Jr.; and Seldin, D.W.:  The Site of Action of Furosemide and Other Sulfonamide Diuretics in the Dog ,  J Clin Invest 44:1458-1469 ( (Sept) ) 1965.Crossref
10.
Walser, M.; Davidson, D.G.; and Orloff, J.:  The Renal Clearance of Alkali-Stable Inulin ,  J Clin Invest 34:1520-1523 ( (Oct) ) 1955.Crossref
11.
Smith, H.W., et al:  The Renal Clearances of Substituted Hippuric Acid Derivatives and Other Aromatic Acids in Dog and Man ,  J Clin Invest 24: 388-404 ( (May) ) 1945.Crossref
12.
Lassiter, W.E.; Gottschalk, C.W.; and Mylle, M.:  Micropuncture Study of Net Transtubular Movement of Water and Urea in Nondiuretic Mammalian Kidney ,  Amer J Physiol 200:1139-1147 ( (June) ) 1961.
×