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 androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.
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 pressure, low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women, and as a part of transgender hormone therapy in transgender women. Spironolactone is taken by mouth.
ATC code C03Diuretics is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup C03 is part of the anatomical group C Cardiovascular system.
Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine and leading to hypokalemia. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.
Drospirenone is a progestin medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is taken by mouth.
An antimineralocorticoid, MCRA, or an aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure. Spironolactone, the first member of the class, is also used in the management of hyperaldosteronism and female hirsutism. Most antimineralocorticoids, including spironolactone, are steroidal spirolactones. Finerenone is a nonsteroidal antimineralocorticoid.
Eplerenone, sold under the brand name Inspra, is a steroidal antimineralocorticoid of the spirolactone group that is used as an adjunct in the management of chronic heart failure and high blood pressure, particularly for patients with resistant hypertension due to elevated aldosterone. Classed as a selective aldosterone receptor antagonist (SARA), it is similar to the diuretic spironolactone, though it is much more selective for the mineralocorticoid receptor in comparison, and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction. Eplerenone is a potassium-sparing diuretic, meaning that it helps the body get rid of water but still keep potassium.
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone which is used as a diuretic in Europe, including in Italy and Belgium. It is also an important active metabolite of spironolactone, and partially accounts for its therapeutic effects.
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-spirolactosteroids, or simply 17α-spirolactones, which feature their spirolactone group at the C17α position. They are antimineralocorticoids, or antagonists of the mineralocorticoid receptor, and have been employed clinically as potassium-sparing diuretics. Some also possess progestogenic and/or antiandrogen properties, which have both contributed to side effects and been utilized for medical indications. The spirolactones were developed by G. D. Searle & Company in the 1950s and thereafter and were denoted as "SC" compounds.
Prorenone is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed. It is the lactonic form of prorenoic acid (prorenoate), and prorenoate potassium (SC-23992), the potassium salt of prorenoic acid, also exists. Prorenoate potassium is about 8 times more potent than spironolactone as an antimineralocorticoid in animals, and it may act as a prodrug to prorenone. In addition to the mineralocorticoid receptor, prorenone also binds to the glucocorticoid, androgen, and progesterone receptors. The antiandrogenic potency of prorenone in vivo in animals is close to that of spironolactone. Similarly to spironolactone, prorenone is also a potent inhibitor of aldosterone biosynthesis.
Mexrenone is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed. It is the lactonic form of mexrenoic acid (mexrenoate), and mexrenoate potassium (SC-26714), the potassium salt of mexrenoic acid, also exists. In addition to the mineralocorticoid receptor, mexrenone also binds to the glucocorticoid, androgen, and progesterone receptors. Relative to spironolactone, it has markedly reduced antiandrogen activity. Eplerenone is the 9-11α-epoxy analogue of mexrenone.
Finerenone is a nonsteroidal antimineralocorticoid that is in phase III clinical trials for the treatment of chronic kidney disease in people with type II diabetes as of October 2015. It has less relative affinity to other steroid hormone receptors than currently available antimineralocorticoids such as eplerenone and spironolactone, which should result in fewer adverse effects like gynaecomastia, impotence, and low libido.
Mespirenone (INN), also known as Δ1-15β,16β-methylenespironolactone, is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed. Animal research found that it was 3.3-fold more potent as an antimineralocorticoid relative to spironolactone. In addition to its antimineralocorticoid properties, mespirenone is also a progestogen, antigonadotropin, and antiandrogen. It is 2- to 3-fold as potent as spironolactone as a progestogen and antigonadotropin but its antiandrogenic activity is markedly reduced and weak in comparison. Mespirenone is also a potent and specific enzyme inhibitor of 18-hydroxylase and thus of mineralocorticoid biosynthesis. The drug was under development by Schering and reached phase II clinical trials but was discontinued in 1989.
Spirorenone (INN) is a steroidal antimineralocorticoid of the spirolactone group that was never marketed. Spirorenone possesses 5–8 times the antimineralocorticoid activity of spironolactone in animal studies. The initial discovery of spirorenone was deemed a great success, as no compound with greater antimineralocorticoid activity had been developed since spironolactone in 1957. Moreover, spirorenone itself has virtually no affinity for the androgen receptor while its progestogenic activity shows species differences, being somewhat greater than that of spironolactone in rabbits but absent in mice and rats. As such, it was characterized as a highly potent antimineralocorticoid with far fewer hormonal side effects relative to spironolactone.
Spiroxasone is a synthetic, steroidal antimineralocorticoid of the spirolactone group which was developed as a diuretic and antihypertensive agent but was never marketed. It was synthesized and assayed in 1963. The drug is 7α-acetylthiospirolactone with the ketone group removed from the C17α spirolactone ring. Similarly to other spirolactones like spironolactone, spiroxasone also possesses antiandrogen activity.
Dicirenone is a synthetic, steroidal antimineralocorticoid of the spirolactone group which was developed as a diuretic and antihypertensive agent but was never marketed. It was synthesized and assayed in 1974. Similarly to other spirolactones like spironolactone, dicirenone also possesses antiandrogen activity, albeit with relatively reduced affinity.
7α-Thiomethylspironolactone is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and the major active metabolite of spironolactone. Other important metabolites of spironolactone include 7α-thiospironolactone, 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (SC-9376).
6β-Hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS) is a steroidal antimineralocorticoid of the spirolactone group and a major active metabolite of spironolactone. Other important metabolites of spironolactone include 7α-thiospironolactone, 7α-thiomethylspironolactone, and canrenone (SC-9376).
7α-Thiospironolactone is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and a minor active metabolite of spironolactone. Other important metabolites of spironolactone include 7α-thiomethylspironolactone, 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (SC-9376).
The pharmacodynamics of spironolactone, an antimineralocorticoid and antiandrogen medication, concern its mechanisms of action, including its biological targets and activities, as well as its physiological effects. The pharmacodynamics of spironolactone are characterized by high antimineralocorticoid activity, moderate antiandrogenic activity, and weak steroidogenesis inhibition. In addition, spironolactone has sometimes been found to increase estradiol and cortisol levels and hence could have slight indirect estrogenic and glucocorticoid effects. The medication has also been found to interact very weakly with the estrogen and progesterone receptors, and to act as an agonist of the pregnane X receptor. Likely due to increased activation of the estrogen and/or progesterone receptors, spironolactone has very weak but significant antigonadotropic effects.
