Thalidomides

Thalidomides refer to a family of chemical compounds derived from thalidomide, including the parent molecule and related analogs used in medicine. These compounds are chiral, and thalidide products are typically used as racemates or as specific enantiomeric formulations; enantiomers may interconvert in the body, which has implications for both efficacy and safety.

History and regulation have shaped the modern use of thalidomides. Thalidomide was introduced in the late 1950s as a sedative and antiemetic for pregnant women. It was linked to widespread birth defects, particularly limb malformations, leading to its withdrawal in the early 1960s. The episode spurred comprehensive changes in drug testing, labeling, and regulatory oversight, culminating in strict risk-management requirements for medicines with teratogenic potential.

Pharmacology and mechanism are complex and continue to be studied. Thalidomide exhibits anti-inflammatory and anti-angiogenic effects, including inhibition of tumor necrosis factor-alpha and modulation of cytokines. A key modern understanding involves binding to cereblon, part of an E3 ubiquitin ligase complex, which influences the activity of transcription factors and immune cells. These actions underlie both therapeutic uses and the drug’s teratogenic risk. Because of enantiomer interconversion and sensitive developmental processes, exposure during pregnancy can cause congenital abnormalities.

Clinical use and derivatives have evolved. Thalidomides and certain analogs are used for conditions such as erythema nodosum leprosum and multiple myeloma, often in combination with corticosteroids. Derivatives like lenalidomide and pomalidomide offer different potency and safety profiles and are subject to their own regulatory controls.

Safety and regulation remain central. Products containing thalidomide are typically distributed under strict risk-evaluation and mitigation programs, with requirements such as pregnancy testing and controlled access. Common adverse effects include neuropathy, thromboembolism, fatigue, constipation, and rash.