Drugs thalidomide

A tragedy occurred in Europe during the 1950s involving the drug thalidomide. This is a powerful sedative and antinausea agent that was considered... 

There are many examples of systems for which one or more important responses were unknown. One of the most tragic involved the drug thalidomide. It was known that one of the responses thalidomide produced when administered to humans was that of a tranquilizer it was not known that when taken during pregnancy it would also affect normal growth of the fetus and result in abnormally shortened limbs of the newborn. 

The macaque embryofetal development study design has been shown to be appropriate for detecting the teratogenic effects of the small molecular weight drugs thalidomide and isotretinoin [35,36]. For large molecular weight biopharmaceuticals that do not cross the placenta the standard macaque... 

ANTICANCER AND IMMUNOMODULATING DRUGS OTHER IMMUNOMODULATING DRUGS Thalidomide... 

There is much that is interesting about the drug thalidomide both historically and scientifically. Thalidomide became infamous and a symbol for aU that was bad about drugs and the drug industry but even this dark cloud has turned out to have a silver lining and there are a number of lessons that can be learnt. 

McHugh SM, Rifkin IR, Deighton J, Wilson AB, Lachmann PJ, Lockwood CM, Ewan PW. The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Thl cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures. Clin Exp Immunol 1995 99(2) 160-7. 

The drug thalidomide serves to illustrate the first of these points with respect to hypnotic potency, the (S)-(—), (ii)-(+) and (i S)-( ) racemate of thalidomide are all equally active, as tested by prolonging of sleep induced by phenobarbitol. (5)-(-)-Thalidomide, but not (/f)-(+)-thali-domide, is transformed in vivo to L-A -phthaloylglutamine and L-Af-phthaloylglutamic acid, products that are both embryotoxic and teratogenic in SWS mice and Natal rats. The d isomers of these products, formed by the drug, are not. ... 

A few years later, Blaschke designed purely synthetic chiral stationary phases obtained by emulsion polymerization of acrylamides prepared from amino acids [17]. These phases had been developed for preparative purposes and proved to be very efficient for the preparative resolution of various chiral drugs for which the enantiomers have been isolated for the first time. These earher applications include the separation of the enantiomers of the sadly well-known drug thalidomide (Fig. 6.2) [18],... 

The earliest of these developmental abnormalities involve the brain stem. In a unique case, Rodier et al. (1996) reported the nearly complete absence of the superior olive and facial nerve nucleus, with shortening of the brain stem between facial nerve nucleus and the trapezoid body. They concluded that the initiating injury in this autistic brain occurred around the time of neural tube closure, which occurs at about 4 weeks of fetal development (O Rahilly and Muller, 1994). This timing also corresponds to an increased incidence of autism following exposure to the drug thalidomide during pregnancy (Rodier and Hyman, 1998 Miller et al., 2005). 

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