Antiglucocorticoid drugs are a class of medications that act to reduce the effects of

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

s, primarily

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

, in the body. They include direct

glucocorticoid receptor The glucocorticoid receptor (GR or GCR) also known by its gene name ''NR3C1'' ( nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol. The GR is expressed in almost every cell in the bod ...

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.mifepristone Mifepristone, and also known by its developmental code name RU-486, is a drug typically used in combination with misoprostol to bring about a medical abortion during pregnancy. This combination is 97% effective during the first 63 days (9 wee ...

and

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

s such as metyrapone,

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

, and

aminoglutethimide Aminoglutethimide (AG), sold under the brand names Elipten, Cytadren, and Orimeten among others, is a medication which has been used in the treatment of seizures, Cushing's syndrome, breast cancer, and prostate cancer, among other indications. ...

. They are used to treat

Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...

. These drugs have also been investigated for their potential therapeutic benefits in various psychiatric disorders, particularly depression and

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

. The rationale behind using antiglucocorticoids in psychiatry stems from the observed dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in many psychiatric conditions, which often manifests as elevated cortisol levels.

Types

There are several types of antiglucocorticoid drugs, including: # Cortisol synthesis inhibitors: These drugs, such as metyrapone,

, and

, work by blocking the production of

in the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

s. # Glucocorticoid receptor antagonists:

Mifepristone Mifepristone, and also known by its developmental code name RU-486, is a drug typically used in combination with misoprostol to bring about a medical abortion during pregnancy. This combination is 97% effective during the first 63 days (9 wee ...

(RU-486) is the primary example of this class, which directly blocks the action of cortisol at its receptor sites. # Steroid hormones:

Dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It funct ...

(DHEA) has been studied for its potential antiglucocorticoid effects.

Therapeutic applications

Cushing's syndrome

Antiglucocorticoid drugs are a treatment option for Cushing's syndrome, a condition characterized by excessive cortisol production. These medications are primarily used in two scenarios: as preoperative treatment to manage symptoms and reduce surgical risks, and as a long-term solution when surgery has failed or is not feasible. The main antiglucocorticoid agents employed in treating Cushing's syndrome include

steroidogenesis inhibitor A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of drug which inhibits one or more of the enzymes that are involved in the process of steroidogenesis, the biosynthesis of endogenous steroids and steroid ho ...

s such as metyrapone and

, which block cortisol production, and

mifepristone Mifepristone, and also known by its developmental code name RU-486, is a drug typically used in combination with misoprostol to bring about a medical abortion during pregnancy. This combination is 97% effective during the first 63 days (9 wee ...

(RU-486), which directly antagonizes the

. Metyrapone and ketoconazole are often preferred as first-line pharmacological treatments, either as monotherapy or in combination, due to their efficacy in controlling hypercortisolemia. However, careful monitoring is essential during treatment, as these drugs can potentially cause side effects and, in some cases, lead to

adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids (primarily cortisol), mineraloco ...

. While antiglucocorticoid therapy has shown promise in managing Cushing's syndrome, it is generally considered an adjunctive treatment to surgery, which remains the definitive cure for most cases of the disorder.

Psychiatric disorders

The use of antiglucocorticoid drugs for psychiatric disorders has yielded mixed results. Some studies have shown promise in treating major depression, particularly in cases with psychotic features. However, a Cochrane review of antiglucocorticoid treatments for psychosis found no significant differences in overall psychotic symptoms, positive symptoms, or negative symptoms when compared to placebo. The mechanism of action for antiglucocorticoid drugs in psychiatric disorders is not fully understood. One hypothesis suggests that these drugs may work by reducing glucocorticoid enhancement of

corticotropin-releasing hormone Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress responses. It is a releasing hormone that b ...

(CRH) action in certain brain regions, such as the central nucleus of the

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

. Additionally, these drugs may affect glucocorticoid receptor regulation, neuroactive steroids, and classical monoamine systems.

References

{{Glucocorticoidics Antiglucocorticoids

Types

Therapeutic applications

Cushing's syndrome

Psychiatric disorders

See also

References