THALIDOMIDE (Thalidomid; synonym: Contergan, Distaval, Neosedyn, Soltenon, Talargan etc.) — teratogenic substance. N-alfa-Ftalilimidoglyutarimid; With 13 H 10 N 2 O 4 ;
In 1957 it was offered by pharmaceutical «Gryunental» (Germany) as a lung sedative and a hypnagogue. Drug was widely advertized and quickly won popularity. Its began to release in a number of the countries of Western Europe and Japan. In the USSR the thalidomide was not allowed for medical use, was not made and not bought. By 1961 consumption of drug abroad made apprx. 1400 kg a month. The same year appeared soobshcheniya7 the numbers of malformations of extremities indicating communication between growth at newborns and reception of T. women during pregnancy. In 1961 — 1962 drug was withdrawn from sale. However many thousands of children with malformations in Western Europe, Japan, Australia, Brazil, Canada were born by this time.
Teratogenic effect of T. it is shown first of all by anomalies of extremities — from small defects up to absence humeral and femurs, and also bones of a forearm and a shin (see Malformations). At such malformation of a brush and foot are directly connected according to a shoulder and pelvic girdle (fokomeliya). (Amelia), anomalies of an outside and inner ear, a hemangioma of the person, an atresia of a gullet and duodenum, an aplasia of a gall bladder, a microphthalmia, damages of cherepnomozgovy nerves, anomalies of heart, vessels, etc. are characteristic of a so-called talidomidny syndrome also total absence of extremities. Splitting of an upper lip and the sky meets seldom.
At anamnestic researches it was established that teratogenic action on an embryo of the person T. renders at early stages of development (in the first trimester of pregnancy). Concerning the size of a teratogenic dose of T. there is no consensus. There are data that T. can cause teratogenic effect even at a single dose in a dose of 0,1 g. At all pregnant women accepting T., children with malformations were born in 20 — 25% of cases. At different types a lab. animals, including dogs and monkeys (except for a closed line of the New Zealand rabbits), T. does not show teratogenic action that testifies to exclusively high specific sensitivity of embryos of the person to it. Nek-ry scientists explain it with features of metabolism of T. in a human body. So, in the course of biotransformation of T. at the person it is formed ftalilimid, having teratogenic properties. At dogs biotransformation of a thalidomide happens to formation of gluta-rimidny and ftalilimidny derivatives.
Mechanism of teratogenic action of T. it is not found out. Assume that T. breaks exchange of glutamic acid (see) since metabolites of this drug are close to it on structure and can be her antagonists. There are also other points of view, according to the Crimea in the mechanism of teratogenic effect of T. blockade of exchange of vitamins of group B, interaction of a thalidomide with nucleinic to-tami and its antimitotic properties matter (see the Teratogenesis).
See also Side effects of pharmaceuticals .
Bibliography: Dyban A. P. Some urgent problems of an experimental teratology, Vestn. USSR Academy of Medical Sciences, No. 1, page 18, 1967, bibliogr.; Chernukh A. M. and Alexandrov P. N. O teratogenic effect of chemical (medicinal) substances, page 26, M., 1969.
B. I. Lyubimov.