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.
FLANIGAN WJ, ACKERMAN GL. Site of Action of Ethacrynic Acid. Arch Intern Med. 1966;118(2):117-122. doi:10.1001/archinte.1966.00290140021005