Investigational Drug Details
| Drug ID: | D344 |
| Drug Name: | Spironolactone |
| Synonyms: | Spironolattone |
| Type: | Chemical drug |
| DrugBank ID: | DB00421 |
| DrugBank Description: | Spironolactone is a potassium sparing diuretic like that competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention.. Spironolactone was originally developed purely for this ability before other pharmacodynamic properties of the drug were discovered. It is indicated to treat a number of conditions including heart failure, deem, hyperaldosteronism, adrenal hyperplasia, hypertension, and nephrotic syndrome. Off label uses of spironolactone involving its antiandrogenic activity include hirsutism, female pattern hair loss, and adult acne vulgaris. Spironolactone is also frequently used in medical gender transition. Spironolactone was developed in 1957, marketed in 1959, and approved by the FDA on January 21, 1960. |
| PubChem ID: | 5833 |
| CasNo: | 52-01-7 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C[C@@]12[C@]3(CC[C@H]1[C@H]1[C@H](CC2)[C@]2(C)C(=CC(=O)CC2)C[C@H]1SC(=O)C)OC(=O)CC3 |
| Structure: |
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| InChiKey: | LXMSZDCAJNLERA-ZHYRCANASA-N |
| Molecular Weight: | 416.583 |
| DrugBank Targets: | Mineralocorticoid receptor antagonist; Androgen receptor antagonist; Progesterone receptor agonist; Glucocorticoid receptor antagonist; Cytochrome P450 11B2, mitochondrial antagonist; Steroid 17-alpha-hydroxylase/17,20 lyase antagonist; 3-oxo-5-alpha-ster |
| DrugBank MoA: | Spironolactone competitively inhibits aldosterone dependant sodium potassium exchange channels in the distal convoluted tubule. This action leads to increased sodium and water excretion, but more potassium retention. The increased excretion of water leads to diuretic and also antihypertensive effects. |
| DrugBank Pharmacology: | Originally spironolactone was only studied for its potassium sparing diuretic effect. Spironolactone competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention.. Inhibition of this receptor leads to increased renin and aldosterone levels. Spironolactone is structurally similar to progesterone and as a result is associated with progestogenic and antiandrogenic effects. |
| DrugBank Indication: | Spironolactone is indicated for the treatment of New York Heart Association Class III-IV heart failure, management of edema in cirrhotic adults not responsive to fluid and sodium restrictions, primary hyperaldosteronism short-term preoperatively, primary hyperaldosteronism long-term in patients with aldosterone producing adrenal adenomas that are not candidates for surgery or patients with bilarteral micro/macronodular adrenal hyperplasia, as an add-on therapy in hypertension, and in nephrotic syndrome when treatment of the disease as well as fluid and sodium restriction with other diuretics is inadequate. Spironolactone has antiandrogenic activity which leads to many of its off label uses. Spironolactone is used off label in the treatment of hirsutism, female pattern hair loss, and adult acne vulgaris. Spironolactone is also frequently used for its antiandrogenic effects in transgender female patients due to its low cost and reducing male-pattern hair growth. |
| Targets: | AR antagonist; PGR agonist; NR1I2 |
| Therapeutic Category: | Diuretic drug |
| Clinical Trial Progress: | Phase 1&2 on-going (NCT03576755) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0102 | NCT01147523 | Phase 2 | Completed | No Results Available | January 2010 | January 20, 2012 | Details |
| L0282 | NCT03576755 | Phase 1/Phase 2 | Recruiting | No Results Available | January 9, 2019 | August 25, 2021 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A01647 | 34669319 | Minerva Endocrinol (Torino) | Effect of spironolactone on pharmacological treatment of nonalcoholic fatty liver disease. | Details |
| A06965 | 32684739 | World J Gastroenterol | Medications in type-2 diabetics and their association with liver fibrosis. | Details |
| A08959 | 31925474 | Naunyn Schmiedebergs Arch Pharmacol | Spironolactone reversed hepato-ovarian triglyceride accumulation caused by letrozole-induced polycystic ovarian syndrome: tissue uric acid-a familiar foe. | Details |
| A12408 | 30467685 | Hormones (Athens) | Noggin levels in nonalcoholic fatty liver disease: the effect of vitamin E treatment. | Details |
| A16336 | 28452101 | Diabetes Obes Metab | Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial. | Details |
| A20917 | 25646700 | Liver Int | Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis. | Details |
| A22996 | 24129399 | Am J Physiol Endocrinol Metab | Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet. | Details |
| A25811 | 21436212 | J Renin Angiotensin Aldosterone Syst | Effect of spironolactone and vitamin E on serum metabolic parameters and insulin resistance in patients with nonalcoholic fatty liver disease. | Details |
| A46221 | 20211973 | Endocrinology | Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. | Details |
| A47857 | 30759233 | J Clin Endocrinol Metab | Massive Ovarian Growth in a Woman With Severe Insulin-Resistant Polycystic Ovary Syndrome Receiving GnRH Analogue. | Details |