Thalidomide

see also: Etymology of Thalidomide

The thalidomide was a drug sold during the Années 1950 and 1960 like hypnogene and in the expectant mothers like Antiémétique to fight morning nauseas and other symptoms. It was synthesized in West Germany in 1953 and was marketing by the firm Grünenthal (Stolberg-lès- Aachen) of October 1st 1957 at 1961, mainly in Germany and Great Britain.
Ce drug was available in approximately 50 countries, but not with the the United States, under at least 40 different names ( Softénon , Talimol, Kevadon, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, etc).

They are only three years later (1960-61) ques the epidemiologists noted a teratogenic effect on the fetal development , in the most visible way as causes Amélie or of Phocomélie (induced by the capacity of the drug to inhibit the Angiogénèse - while interfering with the development of the blood-vessels of the fetus, especially in the event of catch during the 25 to the first 50 days of the Grossesse. The molecule has an effect of intercalation in the molecules of DNA.
Environ 15 000 fetuses were affected by the thalidomide, among which 12 000 in 46 countries were born with congenital defects. Among them, only 8 000 lived beyond one year. In this beginning of XXIe century, the majority of the survivors are still in life, almost all with handicaps caused by the drug. Later, it was discovered that the handicaps and deformations of many survivors to thalidomide were transmitted to their own children by the means of DNA modified. But at present, there is a controversy on this subject.

It is again used nowadays like orphan Médicament in the treatment of the Lèpre and the érythémateux Lupus disseminated (LEAD) but its only indication retained in France east in the treatment of the multiple myélomes resistant to the Chimiothérapie, allowing the lengthening of the lifespan of the patients reached of this type of serious hematologic cancer. Its regulation is limited to one month among women which can procreate

Leprosy symptoms (ENL, erythema nodosum leprosum), in HIV related symptoms by reducing ignition (blocking TNF), for advanced Multiple myeloma, Prostate cancer, Glioblastoma, and Crohn' S disease. -->

The tragedy of thalidomide

The failure off thesis tests to discover the drug' S disastrous consequences highlighted the inadequacy off testing methodologies in uses At that time. Intensive This resulted in year increase in animal testing across has broad arranges species in varying training courses off off pregnancy and lifecycle. In fact, later tests did demonstrate that administering thalidomide to nap strains off pregnant rats reduces the number in the litter by 50%, and giving it to rabbits produces characteristic deformities in the offspring. Yew adequate gold not-animal testing had been gives, thalidomide might never cuts been approved to Be sold anywhere. Summon opponents off Animal testing still quotes thalidomide (nap would say incorrectly) off ace year example the ineffectiveness off such testing

In 1960, Chemie Grünenthal decided to expand into the United States, and applied to the Food and Drug Administration for approval to salt the drug. This approval was not expected to Be controversial, and the box was given to the agency' S newest reviewer, Frances Oldham Kelsey. Kelsey had previously gives animal toxicity research (including effects in pregnancy), and refused to clear thalidomide for salts until she obtained better documentation off its effects, especially in light off nap unusual neurological side effects being reported in Britain. In fact, the testing had not been performed adequately, and satisfactory documentation was not forthcoming.

Though the US marketer William S. Merrell Company was increasing presses to cuts it cleared for salts, Kelsey held out for more toxicity dated before coming to has decision. The decision was pre-empted by births throughout the world giving obviousness off thalidomide' S effect one the embryo, and the manufacturers quickly withdrew to their application. Kelsey' S delay probably prevented thousands off deformities in US the, and made her has national hero. In August 1962, Kelsey was awarded the President' S award for distinguished Federal Civilian Service (the highest civilian award in US the) by President John F. Kennedy. -->

Technical details

Thalidomide has as a formula: (C₁₃H₁₀N₂O₄; phtalimido-glutarimide; one of the many systematic names is the 2 (2,6-dioxo-3-pipéridinyl) - 1H-isoïndole-1,3 (2H) - dione). It is a Médicament Sédatif and Hypnotique.

It exists under two enantiomer S, the forms L and D not having the same effects. The form L protects from nauseas and inhibits the production of TNFα (what has as a consequence its effectiveness in the treatment of certain tumors or inflammatory syndrome), the other has teratogenic effects. Nevertheless, the two forms being able to in vivo convert one into the other, it is illusory to hope to avoid the teratogenic effect by managing only one form.

Chemical analogues of the laevogyrous shape of the thalidomide were developed of which the Lénalidomide. This last could have the effectiveness of the molecule mother without having the side effects of them.

Fiction

Only one tablet , telefilm German in two parts of Adolf Winkelmann was carried out in 2006 on the tragedy of the thalidomide regulation and the fictitious combat of one of its victims. Its diffusion was disputed in justice by the manufacturer Grünenthal , who finally obtained only minor modifications. The first diffusion took place in November 2007.

External bond

Thalidomide - annotated List of Bonds (languages in: + of:)
- Canadian Association of the Victims of Thalidomide
- File on thalidomide with the files of Radio-Canada

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