chapter  25
16 Pages

Thalidomide

WithJames L. Schardein, Orest T. Macina

Thalidomide is a widely known agent that when introduced into the marketplace in Europe, was promoted as a sedative/hypnotic. In the human, thalidomide is a well-known and prototypic teratogen, being responsible for about 8000 infants born in the early 1960s with prominent deformities of the limbs and other organs. Thalidomide was first synthesized in 1953 by Chemie Grunenthal in Germany, and clinical trials proceeded in 1954. The history of the thalidomide disaster would be incomplete without discussing what we have learned from the event. Several steps in the pathway depend on the activation of genes with primarily GC Sp-1 binding site promoters. Thalidomide specifically binds to these promotor sites and inhibits the transcription of those genes. One major positive event resulting from the thalidomide tragedy was a tightening of laws regulating drug safety testing. Thalidomide is a hydrophilic compound that is near average size and of larger polarity compared to the other human developmental toxicants.