The pleiotropic effects of ethacrynic acid.
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⁺-2Cl⁻ 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.
Somberg
John C
JC
Department of Pharmacology and Medicine, Division of Clinical Pharmacology, Rush University, Chicago, IL, USA. jsomberg@rush.edu
Molnar
Janos
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005901:Glaucoma / Q000188:drug therapy / Q000473:pathology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004232:Diuretics; D004791:Enzyme Inhibitors; D011838:Radiation-Sensitizing Agents; D005982:Glutathione Transferase; D004976:Ethacrynic Acid