Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal

antimineralocorticoid An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is ofte ...

of the

spirolactone Spirolactones are a class of functional group in organic chemistry featuring a cyclic ester attached spiro to another ring system. The name is also used to refer to a class of synthetic steroids, called steroid-17α-spirolactones, 17α-spiro ...

group related to

spironolactone Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...

which is used as a

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...

, including in

Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical ...

and

Belgium Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...

. It is also an important active metabolite of spironolactone, and partially accounts for its therapeutic effects.

Medical uses

Canrenone is mainly used as a

. Canrenone has been found to be effective in the treatment of

hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...

in women.

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 Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. Along with NT-proBNP, BNP is one ...

(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. Another study concluded that treatment with canrenone in patients with chronic heart failure improves diastolic function and further decreased BNP levels.

Pharmacology

Pharmacodynamics

Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as an

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...

. Similarly to spironolactone, canrenone inhibits steroidogenic enzymes such as 11β-hydroxylase,

cholesterol side-chain cleavage enzyme Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reactio ...

17α-hydroxylase Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously exp ...

17,20-lyase Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously exp ...

, and

21-hydroxylase Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone a ...

, but once again, is comparatively less potent in doing so.

Pharmacokinetics

The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of canrenone is about 16.5 hours.

As a metabolite

Canrenone is an

active Active may refer to: Music * ''Active'' (album), a 1992 album by Casiopea * Active Records, a record label Ships * ''Active'' (ship), several commercial ships by that name * HMS ''Active'', the name of various ships of the British Royal ...

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

History

Canrenone was described and characterized in 1959. It was introduced for medical use, in the form of potassium canrenoate (the

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

of canrenoic acid), by 1968.

Society and culture

Generic names

''Canrenone'' is the and 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

, although potassium canrenoate remains marketed in various other countries as well.

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

, titlestyle = background:#ccccff , list1 = {{Androgen receptor modulators {{Mineralocorticoid receptor modulators {{Progesterone receptor modulators 11β-Hydroxylase inhibitors 21-Hydroxylase inhibitors Aldosterone synthase inhibitors Antimineralocorticoids Cholesterol side-chain cleavage enzyme inhibitors CYP17A1 inhibitors Diuretics Human drug metabolites Lactones Pregnanes Progestogens Spiro compounds Spirolactones Spironolactone Steroidal antiandrogens World Anti-Doping Agency prohibited substances Conjugated dienes Enones