Contergan - Thalidomide

Monser, C. Contergan/Thalidomid Ein Unglhck kommtselten allein. Dtisseldorf Eggcup Verlag, 1993. Moore, T. Deadly Medicine. New York Simon Schuster, 1995. 

A well known example of tragic consequences is provided by "Thalidomide" (or "Contergan") which was commercialised in the 60 s whereas the (/ )-enantiomer shows a weak sedative activity, the enantiomer of (5)-configuration, administered together in the racemate, caused in the expectant mothers a teratogenic effect (malformations) on the foetus. 

There are many conspicuous examples of different actions by enantiomeric isomers of the molecules of various drugs. Suffice it to mention thalidomide, which was known as Contergan in Europe and with which many tragedies were connected before it was withdrawn from the market. Since 1992, the United States Food and Drug Administration and the European Committee for Proprietary Medicinal Products have required manufacturers to research and characterize each enantiomorph of a potential drug. ... 

Pregnancy (A). Limb malformations induced by the hypnotic thalidomide (Contergan) first focused attention on the potential of drugs to cause malformations (teratogenicity). Drug effects on the unborn fall into two basic categories ... 

In any case however, antipodal helices cause countercurrent spectra of the optical rotation, so that the observation of just a single Cotton effect is sufficient to discriminate the antipodes and, in case, enantiomeric solutes. For such an experiment the choice of the infrared spectral range is no longer dictated by the structure period but by the presence of suitable transition moments. The low demand for the chiral solute to be characterized (Korte, 1978) is exemplified by Fig. 4.6-14. In the 20 im wide sample cell an area of 3 mm times 3 mm was filled with approximately 200 pg solution containing circa 0.2 pg of either S-(-) or R-(-i-) Thalidomide (Contergan) in a nematic solvent. In the spectral interval shown, at least three oppositely shaped ACE are found, the pronounced one around 836 cm is related to the 7 (C- H), phenyl-H out-of-plane vibration of the... 

Hultsch EG, Hartmann J. Nil nocere Die Thalidomid (Contergan) Polyneuritis. [Nil nocere. Thalidomide (Contergan) polyneuritis.) Miinch Med Wochenschr 1961 Nov 3 103 2141. ... 

McFadyen, Thalidomide in America Daemmrich, Tale of Two Experts Kirk, Der Contergan-Fall. 

Estimates come from tallies in Bundesarchiv Koblenz, B142—1826 (Bundesverband der Eltern korpergeschadigter Kinder), and U.S. Food and Drug Administration, New Drug Application 12-611 Kevadon (Thalidomide), volume 1 see also Kirk, Der Contergan-Fall. 

Wenzel, D., and K. Wenzel. Der Contergan-Prozejl (I) Verursachte Thalidomid Nervenschaden und Mifibildungenl Benshein-Auerbach PressebUro Theilacker, 1968. 

Tenoretic atenolol, chlorthalidone thalidomide Contergan, Distaval, Kevadon, Thalomid... 

Even though it has been known for 100 years or more that stereoselectivity plays an important role in drug activity, chiral drugs have been developed and used as race-mates while neglecting the fact that they comprise mixtures of two or more compounds that may have quite different pharmacological properties [98,99]. An example with dramatic consequences is Thalidomide (2-(2,6-dioxo-3-piperidyl)isoindol-l,3-dion, Contergan). 

Thalidomide, marketed under the trade name Contergan , is also a phthalimide derivative, which, because of its extremely teratogenic effects, was used for only a short time as a sedative. 

Thalidomide was developed in West Germany and was first marketed (as Contergan) in 1957 for insomnia, tension, and morning sickness during pregnancy. At that time it was available in more than 40 countries but had not been approved for use in the United States because Frances O. Kelsey, a physician for the Food and Drug Administration (FDA), had insisted upon additional tests to explain a British study that had found nervous system side effects. 

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