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Ethacrynic acid (EC), an effective loop diuretic especially in patients allergic to sulfa-containing drugs, possesses a number of potentially useful actions in addition to the inhibition of the Na+-K +-2CI- kidney symport. Inhibition of the enzyme glutathione S-transferase plays an important role in reducing chemotherapy drug resistance. Chemical modifications of EC increase inhibition of glutathione S-transferase and reduce toxicity due to diuretic action (hypotension and hypovolemia). This work may lead to effective therapies in reducing chemotherapy resistance in cancer chemotherapeutics. In addition, EC or conjurers may be a radiation enhancer, an anti-inflammatory agent, or a treatment for glaucoma.
Dr. J.C. Somberg, American Institute of Therapeutics, 21 N. Skokie Highway, G-3, Lake Bluff, IL, USA. 60044. jsomberg@rush.edu
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)