Teratogen update: thalidomide: a review, with a focus on ocular findings and new potential uses.

نویسندگان

  • M T Miller
  • K Strömland
چکیده

Thalidomide (a-[N-phthalmido]-glutarimide) was synthesized in 1954, in what was then West Germany, by Chemie Grünenthal under the brand name of Contergan and was subsequently licensed in 46 other countries worldwide, covering all continents. It is an odorless white crystalline compound with low solubility in water (McBride, ’77; Stirling et al., ’97). A number of pharmaceutical companies manufactured thalidomide in various concentrations under several trade names (Stirling et al., ’97).Advertisements for the drug claimed that it was helpful in treating anxiety, insomnia, gastritis, and tension and that it was safe and harmless for pregnant women (Lenz, ’88). Additionally, it was an effective antiemetic in pregnancy (McBride, ’77). Thalidomide was first marketed in Germany in October 1957 as an effective, safe, inexpensive sedative, and production in that country reached 14.58 tons by 1960 (Zwingenberger and Wendt, ’96). A liquid form was available for children, and some compounds were sold without prescriptions (Stirling et al., ’97). Routine screening tests found thalidomide to be nontoxic in rodents, and therefore its potent teratogenicity in humans and higher mammals was not anticipated (Brent and Holmes, ’88). In the early 1960s an increasing number of infants were born with hypoplastic limb defects (Lenz,’85). In fall 1961, Lenz, noting these congenital malformations in the German population, suggested a possible correlation with thalidomide taken during pregnancy. He reported his observations at meetings and in the medical literature (Lenz,’61a,b,’62; Lenz and Knapp, ’62). Similar observations were made in England (Smithells, ’62) and Australia (McBride, ’61). Within a few months of the initially reported cases, the drug was withdrawn from commercial sale by Grünenthal (November 1961), and 9 months later was taken off the market in Japan. It was withdrawn from Great Britain in December 1961 (Kida, ’87). The potent teratogenicity appropriately suppressed other uses of thalidomide, such as for anti-inflammatory effects (Somers, ’60, Miller et al., ’60). The U.S. Food and Drug Administration (FDA) had not approved the drug for unrestricted use because of concerns (primarily about possible peripheral neuropathy) raised by Francis Kelsey, an FDA physician. Thus the number of cases of thalidomide embryopathy in the United States was small (Kelsey, ’88). The teratogenic effects of thalidomide contributed to the passage of new regulatory legislation for pharmaceuticals (Stirling et al.,’97). There are many reviews in the literature of various aspects of the thalidomide story (McBride, ’77; Fraser, ’88; Kelsey, ’88; Lenz, ’88; Warkany, ’88; Lenz, ’88).

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عنوان ژورنال:
  • Teratology

دوره 60 5  شماره 

صفحات  -

تاریخ انتشار 1999