Search

Experiments on rats showed that diazepam, in a dose of 10 mg/kg by mouth throughout pregnancy, affects the development of the offspring. Changes observed in the behavior of the young rats are evidently due to the activating action of the compound in small doses on the fetus after passing through the placental barrier.

Experiments on rats showed that carbidine, when injected intramuscularly for 2 weeks in a dose effective for the experimental treatment of alcohol dependence (4 mg/kg), has no gonadotropic action. The drug does not potentiate the adverse after-effects of chronic ethanol poisoning on ovogenesis or spermatogenesis and does not delay the course of repair processes in the gonads after cessation of the ethanol intake. However, carbidine is given during continued consumption of ethanol, further development of the regressive changes in the generative cells of the gonads is observed.

It has been established in experiments on mini pigs of Siberian origin that phenazepam given at a dose of 1 mg/kg per os during organogenesis has no embryotoxic or teratogenic action. The drug content in the blood of pregnant animals was determined simultaneously. A conclusion is drawn about perspectiveness of using mini pigs for testing embryotoxic activity of drugs.

The following regularities governing the transplacental passage of chlorpromazine have been established, viz. the drug passes through the placenta only at the end of the pregnancy term; with repeated administration to mothers it accumulates in the placental and fetal tissues and is contained in the organs of the newborn and one-week old animals.

Chronic toxicity of the benzodiazepine series tranquilizer phenazepam (5 and 50 mg/kg) administered per os for 1.3 and 6 months was studied in experiments on white rats, guinea pigs and dogs. It has been shown during varying time of observation that the drug neither decreases weight gain in the animals nor adversly acts on the blood or produces local irritating action. Histopathological changes in some internal organs proved irreversible. Administered at varying periods of pregnancy, phenazepam at an oral dose of 100 mg/kg exerted no embryotoxic or teratogenic action.

The caudate nucleus neurons structure in 21-day old rattlings, whose mothers received chlorpromazine over the whole period of their pregnancy, was studied. The intracellular build-up of the caudate nucleus neurons, the structure of their dendrites and spinae were in these rattlings more perfect than in control animals. The data obtained accord well with the results of physiological observations over the activation of behavioral reactions in the test rattlings as against the control ones.

In experiments on rats it was shown that carbidine injected intramuscularly for two weeks does not effect gonadotropic action in a dose effective in experimental therapy of alcohol dependence (4 mg/kg). The drug neither potentiates adverse after-effects of chronic action of ethanol on ovo- and spermatogenesis nor slows down the course of the reparative processes in the gonads after ethanol is discontinued. However, further regressive changes in the gonadal generative elements were recorded in administering carbidine against the background of continued use of ethanol.

A preclinical study on safety of a new antialcoholic drug inmecarb was carried out on three species of experimental animals (rats, guinea pigs, dogs) receiving the drug at different doses including a subtoxic one (1/5 of LD50) for 6 months. The authors concluded that on the basis of a relatively low toxicity and the absence of specific toxicity and long-term side effects the drug may be recommended for clinical use as an antialcoholic agent.