Thalidomide, teratogenic effects

The glutarimide best known to the lay public, thalidomide (40), owes its reputation not to efficacy, but to the wholly unanticipated and tragic teratogenic effects elicited by this compound. It might be noted that the very efficacy and lack of the usual barbiturate side effects shown by this drug led to its prescription as a hypnotic for expectant mothers. Condensation of the phthalimide of glutamic acid (39) with ammonia at elevated... 

One enantiomer of penicillamine (D-) exhibits antiarthritic properties but foe other is highly toxic (Figure 8.3). The teratogenic effects of thalidomide were induced by one enantiomer, foe other exhibited foe beneficial effects against morning sickness. 

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 is clear evidence from many different sources that the metabolism of compounds may be involved in their teratogenic effects, as will be seen in the final chapter in the discussion of thalidomide and diphenylhydantoin teratogenicity. The embryo and fetus of some species clearly have metabolic activity toward foreign compounds, which may be inducible by other foreign compounds. 

A number of drugs are known to have adverse or teratogenic effects on the developing fetus. The most infamous, of course, is thalidomide (a sedative used during the... 

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... 

Toxicity. Thalidomide has a low acute toxicity in 2 cases of reported overdose there was no evidence of respiratory or cardiac depression. Thalidomide has teratogenic effects when administered to women early in pregnancy. 

Thahdomide is given in a racemic mixture of its two enantiomers, i -thalidomide and 5-thalidomide the former is responsible for its hypnotic effects and the latter for its immunomodulatory and teratogenic effects (16). 

Thalidomide should not be used during pregnancy because of its teratogenic effects (61,98-109). In 46 examined cases of malformations, 41 of the mothers had taken thalidomide, while in the other five cases the possibility could not be ruled out, while among 300 normal controls none of the mothers had taken thalidomide (110). 

The critical phase for teratogenic effects of thalidomide is from the 27th to the 40th day after conception or from the 37th to the 54th day after the first day of the last menstrual period (155). In 12 of 86 cases the date of conception was fairly well known and the narrowest... 

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