Report on Aminoglutethimide (DB00357): A Comprehensive Monograph

Section 1: Executive Summary & Drug Identity

1.1 Overview of Aminoglutethimide: A Historical First-in-Class Agent

Aminoglutethimide is a nonsteroidal small molecule that holds a significant place in the history of endocrine therapy. It is recognized as a first-generation aromatase inhibitor and a potent inhibitor of steroidogenesis.[1] Its clinical journey is a notable case study in pharmaceutical development, marked by serendipitous discovery, drug repurposing, and eventual obsolescence in the face of more targeted and tolerable agents.

Initially introduced in 1960 under brand names such as Elipten, its intended use was as an anticonvulsant for the treatment of petit mal epilepsy.[1] However, its clinical use in this capacity was short-lived. By 1963, reports emerged of the drug inducing symptoms of adrenal insufficiency, a condition akin to Addison's disease.[1] These significant adverse endocrine effects led to its withdrawal from the market as an anticonvulsant in 1966.[1]

The very toxicity that led to its initial withdrawal—the suppression of adrenocortical steroid synthesis—was subsequently recognized as a powerful therapeutic mechanism. This pivotal realization led to the repurposing of aminoglutethimide for conditions characterized by hormonal excess. Beginning in 1969 for breast cancer and 1974 for prostate cancer, it was reintroduced under brand names like Cytadren and Orimeten for the management of Cushing's syndrome and hormone-dependent malignancies.[1] In this new role, it functioned as a "medical adrenalectomy" agent.[3]