Canrenone

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Canrenone
Skeletal formula of canrenone
Ball-and-stick model of the canrenone molecule
Clinical data
Trade names Contaren, Luvion, Phanurane, Spiroletan
Synonyms Aldadiene;[1] 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
AHFS/Drugs.com International Drug Names
ATC code
Pharmacokinetic data
Protein binding 95%
Elimination half-life 10–35 hours
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
ECHA InfoCard 100.012.322 Edit this at Wikidata
Chemical and physical data
Formula C22H28O3
Molar mass 340.456 g/mol
3D model (JSmol)
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Canrenone (brand names Contaren, Luvion, Phanurane, Spiroletan) is a steroidal antimineralocorticoid[2][3] of the spirolactone group related to spironolactone which is used as a diuretic in Europe, including in Italy and Belgium.[4][5][6] It is also an important active metabolite of spironolactone, and partially accounts for its therapeutic effects.[7][8]

Medical uses[edit]

Canrenone is mainly used as a diuretic.[citation needed]

Canrenone has been found to be effective in the treatment of hirsutism in women.[9]

Pharmacology[edit]

Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as an antiandrogen.[10][11] 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.[12]

As a metabolite[edit]

Canrenone is an active metabolite of spironolactone, canrenoic acid, and potassium canrenoate, and is considered to be partially responsible for their effects.[7] It has been found to account for approximately 10 to 25% of the potassium-sparing effect of spironolactone,[13] whereas another metabolite, 7α-thiomethylspironolactone (7α-TMS), accounts for around 80% of the potassium-sparing effect of the drug.[14][15][16]

Pharmacokinetics of spironolactone and metabolites[8]
Compound Cmax (ng/mL)
(day 1)
Cmax (ng/mL)
(day 15)
AUC (ng•hr/ml)
(day 15)
t1/2 (hr)
Spironolactone 72 80 231 1.4
Canrenone 155 181 2173 16.5
7α-TMS 359 391 2804 13.8
6β-OH-7α-TMS 101 125 1727 15.0

Society and culture[edit]

Canrenone is the INN and USAN of the drug.[4][6]

See also[edit]

References[edit]

  1. ^ Jürg Müller (6 December 2012). Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects. Springer Science & Business Media. pp. 164–. ISBN 978-3-642-83120-1. 
  2. ^ Losert, W; Casals-Stenzel, J; Buse, M (1985). "Progestogens with antimineralocorticoid activity". Arzneimittelforschung. 35 (2): 459–71. PMID 4039568. 
  3. ^ Fernandez, MD; Carter, GD; Palmer, TN (1983). "The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol". Br J Clin Pharmacol. 15 (1): 95–101. doi:10.1111/j.1365-2125.1983.tb01470.x. PMC 1427833Freely accessible. PMID 6849751. 
  4. ^ a b Hill, R.A.; Makin, H.L.J.; Kirk, D.N.; Murphy, G.M. (23 May 1991). Dictionary of Steroids. CRC Press. pp. 656–. ISBN 978-0-412-27060-4. 
  5. ^ Romanelli, RG; Gentilini, P (May 2004). "Cross reactivity due to positive canrenone interference". Gut. 53 (5): 772–3. PMC 1774040Freely accessible. PMID 15082604. 
  6. ^ a b Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 167–. ISBN 978-3-88763-075-1. 
  7. ^ a b Clark, Michelle A.; Harvey, Richard A.; Finkel, Richard; Rey, Jose A.; Whalen, Karen (15 December 2011). Pharmacology. Lippincott Williams & Wilkins. pp. 286–. ISBN 978-1-4511-1314-3. 
  8. ^ a b Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, Stubbs K, Smith M, Karim A (1989). "Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites". J Clin Pharmacol. 29 (4): 342–7. doi:10.1002/j.1552-4604.1989.tb03339.x. PMID 2723123. 
  9. ^ Sobbrio, GA; Granata, A; Panacea, A; Trimarchi, F (1989). "Effectiveness of short term canrenone treatment in idiopathic hirsutism". Minerva Endocrinol. 14 (2): 105–8. PMID 2761494. 
  10. ^ Coelingh Benni, H.J.T.; Vemer, H.M. (15 December 1990). Chronic Hyperandrogenic Anovulation. CRC Press. pp. 152–. ISBN 978-1-85070-322-8. 
  11. ^ Seldin, Donald W.; Giebisch, Gerhard H. (23 September 1997). Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. pp. 630–. ISBN 978-0-08-053046-8. 
  12. ^ Colby HD (1981). "Chemical suppression of steroidogenesis". Environ. Health Perspect. 38: 119–27. doi:10.1289/ehp.8138119. PMC 1568425Freely accessible. PMID 6786868. 
  13. ^ Pere Ginés; Vicente Arroyo; Juan Rodés; Robert W. Schrier (15 April 2008). Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. John Wiley & Sons. p. 229. ISBN 978-1-4051-4370-7. 
  14. ^ Maron BA, Leopold JA (2008). "Mineralocorticoid receptor antagonists and endothelial function". Curr Opin Investig Drugs. 9 (9): 963–9. PMC 2967484Freely accessible. PMID 18729003. 
  15. ^ International Agency for Research on Cancer; World Health Organization (2001). Some Thyrotropic Agents. World Health Organization. pp. 325–. ISBN 978-92-832-1279-9. 
  16. ^ Agusti G, Bourgeois S, Cartiser N, Fessi H, Le Borgne M, Lomberget T (2013). "A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone". Steroids. 78 (1): 102–7. doi:10.1016/j.steroids.2012.09.005. PMID 23063964.