Aminoglutethimide

Aminoglutethimide

Aminoglutethimide is a pharmaceutical drug that was initially introduced as an anticonvulsant but later found widespread use in the treatment of certain types of cancer, particularly breast cancer and prostate cancer. It functions by inhibiting the enzyme aromatase, leading to a reduction in estrogen production, which is often a contributing factor in the growth of hormone-sensitive tumors.

History

Aminoglutethimide was first synthesized in the 1950s and initially used to treat epilepsy due to its anticonvulsant properties. However, its use in this capacity was limited due to the development of more effective and less toxic anticonvulsant medications. In the 1970s, researchers discovered its potential in oncology, particularly in treating hormone-sensitive cancers, by inhibiting the synthesis of adrenal steroids, thereby reducing estrogen levels in the body.

Mechanism of Action

The primary mechanism of action of aminoglutethimide is the inhibition of the aromatase enzyme, which is crucial in the biosynthesis of estrogens from androgens. Additionally, it inhibits the enzymatic conversion of cholesterol to pregnenolone, leading to a decrease in the production of all adrenal steroids. This reduction in estrogen production is particularly beneficial in the treatment of estrogen receptor-positive breast cancer, where the growth of cancer cells is stimulated by estrogens.

Clinical Uses

Aminoglutethimide is primarily used in the treatment of hormone-sensitive cancers, such as metastatic breast cancer and prostate cancer. It is often used in patients who have not responded to other forms of treatment or in postmenopausal women. The drug can be used alone or in combination with other therapies, such as corticosteroids, to manage symptoms and inhibit tumor growth.

Side Effects

The use of aminoglutethimide can lead to several side effects, including:

• Fatigue
• Nausea and vomiting
• Rash
• Dizziness
• Hypothyroidism

Due to its effect on adrenal steroid synthesis, it can also cause adrenal insufficiency, necessitating the concurrent administration of corticosteroids to mitigate this risk.

Pharmacokinetics

Aminoglutethimide is well absorbed from the gastrointestinal tract, with its metabolism occurring in the liver. It is excreted primarily in the urine. The drug's half-life allows for twice-daily dosing in most treatment regimens.

Conclusion

While aminoglutethimide has been largely replaced by more selective and less toxic aromatase inhibitors in the treatment of breast and prostate cancers, it remains an important option in certain clinical scenarios. Its development and use have contributed significantly to the understanding and management of hormone-sensitive cancers.