Antiglucocorticoid

Antiglucocorticoid
Drug class
Mifepristone, an antiglucocorticoid that is used in the treatment of Cushing's syndrome.
Class identifiers
Synonyms	Glucocorticoid antagonist; Cortisol antagonist; Anticorticosteroid
Use	Cushing's syndrome, others
Biological target	Glucocorticoid receptor
Chemical class	Steroids
Legal status
In Wikidata

Antiglucocorticoid drugs are a class of medications that act to reduce the effects of glucocorticoids, primarily cortisol, in the body.^[1] They include direct glucocorticoid receptor antagonists such as mifepristone and synthesis inhibitors such as metyrapone, ketoconazole, and aminoglutethimide. They are used to treat Cushing's syndrome.^[2]

These drugs have also been investigated for their potential therapeutic benefits in various psychiatric disorders, particularly depression and psychosis.^[3][4] 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.^[4][5]

There are several types of antiglucocorticoid drugs, including:

1. Cortisol synthesis inhibitors: These drugs, such as metyrapone, aminoglutethimide, and ketoconazole, work by blocking the production of cortisol in the adrenal glands.^[6]
2. Glucocorticoid receptor antagonists: Mifepristone (RU-486) is the primary example of this class, which directly blocks the action of cortisol at its receptor sites.^[3][6]
3. Steroid hormones: Dehydroepiandrosterone (DHEA) has been studied for its potential antiglucocorticoid effects.^[3]

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.^[7][2] The main antiglucocorticoid agents employed in treating Cushing's syndrome include steroidogenesis inhibitors such as metyrapone and ketoconazole, which block cortisol production, and mifepristone (RU-486), which directly antagonizes the glucocorticoid receptor.^[2] Metyrapone and ketoconazole are often preferred as first-line pharmacological treatments, either as monotherapy or in combination, due to their efficacy in controlling hypercortisolemia.^[2] However, careful monitoring is essential during treatment, as these drugs can potentially cause side effects and, in some cases, lead to adrenal insufficiency.^[7] 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.^[2]

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.^[6] 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.^[3]

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 (CRH) action in certain brain regions, such as the central nucleus of the amygdala.^[6] Additionally, these drugs may affect glucocorticoid receptor regulation, neuroactive steroids, and classical monoamine systems.^[6]

• Corticosteroid
• Antimineralocorticoid