canrenone

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 460016527

| IUPAC_name = 10,13-Dimethylspiro[2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-17,5'-oxolane]-2',3-dione

| image = Canrenone.svg

| alt = Skeletal formula of canrenone

| image2 = Canrenone 3D ball.png

| alt2 = Ball-and-stick model of the canrenone molecule

| tradename = Contaren, Luvion, Phanurane, Spiroletan

| Drugs.com = {{Drugs.com|international|canrenone}}

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status =

| routes_of_administration =

| class = Antimineralocorticoid

| bioavailability =

| protein_bound = 95%

| metabolism =

| elimination_half-life = 16.5 hours{{cite journal | vauthors = Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, Stubbs K, Smith M, Karim A | display-authors = 6 | title = Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites | journal = Journal of Clinical Pharmacology | volume = 29 | issue = 4 | pages = 342–347 | date = April 1989 | pmid = 2723123 | doi = 10.1002/j.1552-4604.1989.tb03339.x | s2cid = 29457093 }}

| excretion =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 976-71-6

| ATC_prefix = C03

| ATC_suffix = DA03

| PubChem = 13789

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 13192

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 78O20X9J0U

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1463345

| synonyms = Aldadiene;{{cite book| vauthors = Müller J |title=Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects|url=https://books.google.com/books?id=jmKSBgAAQBAJ&pg=PT164|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-83120-1|pages=164–}} SC-9376; RP-11614; 7α-Desthioacetyl-δ⁶-spironolactone; 6,7-Dehydro-7α-desthioacetylspironolactone; 17-Hydroxy-3-oxo-17α-pregna-4,6-diene-21-carboxylic acid γ-lactone

| C=22 | H=28 | O=3

| SMILES = O=C5\C=C4\C=C/[C@@H]1[C@H](CC[C@]3([C@H]1CC[C@]32OC(=O)CC2)C)[C@@]4(C)CC5

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C22H28O3/c1-20-9-5-15(23)13-14(20)3-4-16-17(20)6-10-21(2)18(16)7-11-22(21)12-8-19(24)25-22/h3-4,13,16-18H,5-12H2,1-2H3/t16-,17+,18+,20+,21+,22-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = UJVLDDZCTMKXJK-WNHSNXHDSA-N

}}

Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antimineralocorticoid{{cite journal | vauthors = Losert W, Casals-Stenzel J, Buse M | title = Progestogens with antimineralocorticoid activity | journal = Arzneimittel-Forschung | volume = 35 | issue = 2 | pages = 459–471 | year = 1985 | pmid = 4039568 }}{{cite journal | vauthors = Fernandez MD, Carter GD, Palmer TN | title = The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol | journal = British Journal of Clinical Pharmacology | volume = 15 | issue = 1 | pages = 95–101 | date = January 1983 | pmid = 6849751 | pmc = 1427833 | doi = 10.1111/j.1365-2125.1983.tb01470.x }} of the spirolactone group related to spironolactone which is used as a diuretic in Europe, including in Italy and Belgium.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA210|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=210–}}{{cite book | vauthors = Hill R, Makin H, Kirk D, Murphy G |title=Dictionary of Steroids |url=https://books.google.com/books?id=qw5X0NK1A90C&pg=PA656 |date=23 May 1991 |publisher=CRC Press |isbn=978-0-412-27060-4 |pages=656–}}{{cite journal | vauthors = Romanelli RG, Gentilini P | title = Cross reactivity due to positive canrenone interference | journal = Gut | volume = 53 | issue = 5 | pages = 772–773 | date = May 2004 | pmid = 15082604 | pmc = 1774040 }}{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA167|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=167–}} It is also an important active metabolite of spironolactone, and partially accounts for its therapeutic effects.

Medical uses

Canrenone has been found to be effective in the treatment of hirsutism in women.{{cite journal | vauthors = Sobbrio GA, Granata A, Panacea A, Trimarchi F | title = Effectiveness of short term canrenone treatment in idiopathic hirsutism | journal = Minerva Endocrinologica | volume = 14 | issue = 2 | pages = 105–108 | year = 1989 | pmid = 2761494 }}

= Heart failure =

Two studies of canrenone in people with heart failure have shown a mortality benefit compared to placebo. In the evaluation which studied people with chronic heart failure (CHF), people that were treated with canrenone displayed a lower number of deaths compared to the placebo group, indicating a death and morbidity benefit of the medication.

One study compared 166 treated with canrenone to 336 given conventional therapy lasting 10 years. Differences in systolic and diastolic blood pressure was observed between both patient groups where, patients treated with canrenone, showed a lower blood pressure compared to conventional therapy. Uric acid was lower in the group treated with canrenone; however, no differences were seen in potassium, sodium, and brain natriuretic peptide (BNP) levels. Left ventricular mass was also lower in the group treated with canrenone and a greater progression of NYHA class was observed in the control group compared to patients treated with canrenone.{{cite journal | vauthors = Derosa G, Maffioli P, Scelsi L, Bestetti A, Vanasia M, Cicero AF, Spinardi L, Bentivenga C, Esposti DD, Caprio M, Borghi C, Pitt B, Cosentino E | display-authors = 6 | title = Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: The COFFEE-IT study | journal = Pharmacological Research | volume = 141 | pages = 46–52 | date = March 2019 | pmid = 30502530 | doi = 10.1016/j.phrs.2018.11.037 | s2cid = 54564252 }}

Another study concluded that treatment with canrenone in patients with chronic heart failure improves diastolic function and further decreased BNP levels.{{cite journal | vauthors = de Simone G, Chinali M, Mureddu GF, Cacciatore G, Lucci D, Latini R, Masson S, Vanasia M, Maggioni AP, Boccanelli A | display-authors = 6 | title = Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study | language = English | journal = Nutrition, Metabolism, and Cardiovascular Diseases | volume = 21 | issue = 10 | pages = 783–791 | date = October 2011 | pmid = 21939839 | doi = 10.1016/j.numecd.2010.02.012 }}

Pharmacology

=Pharmacodynamics=

Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as an antiandrogen.{{cite book | vauthors = Coelingh Benni H, Vemer H |title=Chronic Hyperandrogenic Anovulation |url=https://books.google.com/books?id=q6zqFrCLUoIC&pg=PA152 |date=15 December 1990 |publisher=CRC Press |isbn=978-1-85070-322-8 |pages=152–}}{{cite book | vauthors = Seldin DW, Giebisch GH |title=Diuretic Agents: Clinical Physiology and Pharmacology |url=https://books.google.com/books?id=VHcsrw6unuAC&pg=PA630 |date=23 September 1997 |publisher=Academic Press |isbn=978-0-08-053046-8 |pages=630–}} Similarly to spironolactone, canrenone inhibits steroidogenic enzymes such as 11β-hydroxylase, cholesterol side-chain cleavage enzyme, 17α-hydroxylase, 17,20-lyase, and 21-hydroxylase, but once again, is comparatively less potent in doing so.{{cite journal | vauthors = Colby HD | title = Chemical suppression of steroidogenesis | journal = Environmental Health Perspectives | volume = 38 | pages = 119–127 | date = April 1981 | pmid = 6786868 | pmc = 1568425 | doi = 10.1289/ehp.8138119 | bibcode = 1981EnvHP..38..119C }}

=Pharmacokinetics=

The elimination half-life of canrenone is about 16.5 hours.

=As a metabolite=

Canrenone is an active metabolite of spironolactone, canrenoic acid, and potassium canrenoate, and is considered to be partially responsible for their effects.{{cite book | vauthors = Clark MA, Harvey RA, Finkel R, Rey JA, Whalen K |title=Pharmacology |url=https://books.google.com/books?id=Y558dgp_PjoC&pg=PA286 |date=15 December 2011 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-1314-3 |pages=286–}} It has been found to have approximately 10 to 25% of the potassium-sparing diuretic effect of spironolactone,{{cite book| vauthors = Angeli P, Gatta A | chapter = Medical Treatment of Ascites in Cirrhosis | veditors = Ginés P, Arroyo V, Rodés J, Schrier RW |url=https://www.researchgate.net/publication/227982015 |title=Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment| chapter-url=https://books.google.com/books?id=Z3PARx4oYDgC&pg=PR6|date=15 April 2008|publisher=John Wiley & Sons|isbn=978-1-4051-4370-7|page=229}} whereas another metabolite, 7α-thiomethylspironolactone (7α-TMS), accounts for around 80% of the potassium-sparing effect of the drug.{{cite journal | vauthors = Maron BA, Leopold JA | title = Mineralocorticoid receptor antagonists and endothelial function | journal = Current Opinion in Investigational Drugs | volume = 9 | issue = 9 | pages = 963–969 | date = September 2008 | pmid = 18729003 | pmc = 2967484 }}{{cite book|author1=International Agency for Research on Cancer|author2=World Health Organization|title=Some Thyrotropic Agents|url=https://books.google.com/books?id=l965aqw_LSkC&pg=PA325|year=2001|publisher=World Health Organization|isbn=978-92-832-1279-9|pages=325–}}{{cite journal | vauthors = Agusti G, Bourgeois S, Cartiser N, Fessi H, Le Borgne M, Lomberget T | title = A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone | journal = Steroids | volume = 78 | issue = 1 | pages = 102–107 | date = January 2013 | pmid = 23063964 | doi = 10.1016/j.steroids.2012.09.005 | s2cid = 8992318 }}

{{Pharmacokinetics of 100 mg per day spironolactone and its metabolites}}

History

Canrenone was described and characterized in 1959. It was introduced for medical use, in the form of potassium canrenoate (the potassium salt of canrenoic acid), by 1968.{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA804|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=804–}}

Society and culture

=Generic names=

Canrenone is the {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|USAN|United States Adopted Name}} of the drug.

=Brand names=

Canrenone has been marketed under the brand names Contaren, Luvion, Phanurane, and Spiroletan, among others.

=Availability=

Canrenone appears to remain available only in Italy, although potassium canrenoate remains marketed in various other countries as well.{{Cite web|url=https://www.drugs.com/international/canrenone.html|title = List of Aldosterone receptor antagonists | work = Drugs.com }}{{Cite web|url=https://www.drugs.com/international/potassium-canrenoate.html|title = Potassium Uses, Side Effects & Interactions | work = Drugs.com }}