Analysis of General Toxicity of Ergoferon.

For antibody-based drugs, it is important and relevant to study their toxic effects, which can often become limiting when prescribing this type of therapy. General toxicity of antiviral drug Ergoferon based on technologically processed antibodies was studied on sexually mature animals. Analysis of acute toxicity showed the absence of lethal outcomes when the drug was administered to adult rats at the maximum tolerated doses. In a study of repeated dose toxicity, no adverse effects of the drug were detected.

Safety of the Drug Prospekta: a Preclinical Study of Acute and Repeated Dose Toxicity.

General toxic effect of the drug Prospekta (modified affinity purified antibodies to the brain-specific S100 protein) was studied on mature male and female mice and rats: acute toxicity with double intragastric and intraperitoneal administration of the maximum permissible doses at a 2-h interval, repeated dose toxicity with intragastric administration of the maximum permissible and close to therapeutic doses for 6 months. No lethal and toxic effects on animals were observed, including no toxic effects on vital systems, i.e., CNS and cardiovascular system, as well systems with the functions that may be temporarily disrupted (excretory and digestive systems). All the differences between animals of the experimental and control groups varied within the physiological range. It can be concluded that the drug produces no general toxic effect on laboratory animals.

Effects of a New Benzimidazole Derivative with Actoprotective Properties on Spermatogenic Epithelium of the Testes and Fertility of Male White Rats.

The effects of a new derivative of benzimidazole (K-134) in doses of 5 and 50 mg/kg on the spermatogenesis and fertilizing ability of spermatozoa were studied on male rats. It was found that 2-month course treatment with the studied substance enhances the producing ability of the spermatogenic epithelium and improves fertilizing ability of spermatozoa.

Effects of Afobazole on Postnatal Development of Rat Offspring.

Physical development, development of sensory and motor reflexes, behavioral and mnestic patterns were studied infantile and juvenile rat pups born by female rats receiving Afobazole during pregnancy. Physical development and development of sensory and motor reflexes in rats were completed without pathologies by the age of 2 months. During the infantile period, the rat pups demonstrated reduced body weight gain, delayed eye opening and pupillary response formation, decreased muscle force, and suppressed motor behavior. During the juvenile period, body weight gain and development of motor behavior were intensified. Females demonstrated later vagina opening and poorer mnestic responses. In males, the terms of sexual maturation were unchanged and processes of learning and memory retrieval were not impaired.

[PHYSICAL AND BEHAVIORAL DEVELOPMENT OF THE OFFSPRING OF FEMALE RATS TREATED WITH AFOBAZOLE DURING PREGNANCY.]

It is experimentally established that afobazole produces no damaging action on the organogenesis and fetogenic processes registered in the postnatal period of rat offspring development. It was noted that, in rat babies in lactation age, the dynamics of body weight gain was lower on average by 7.4% (p < 0.05) in males and 17.0% (p < 0.001) in females; the rate of muscular force maturing was lower by 2.7% (p < 0.05); and the locomotive activity was lower (by 19.4% for ver- tical standings and by 50% for looking into floor holes, p < 0.05) compared to control values. For the same offspring passed to definitive food, the body weight gain and behavioral activity did not differ from control indicators, while the terms of sexual development were delayed in females and did not change in males. By two-month age, the physical development of rat offspring was completely created and met physiological standards.

Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects.

We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity-purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity-purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-γ and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity.

[INFLUENCE OF A NEW SUBSTANCE WITH ANTIDEPRESSANT ACTIVITY ON ORGANO- AND FETOGENESIS PROCESSES REGISTERED DURING ANTHENATAL PERIOD.]

Experiments on pregnant female rats showed that the beta-phenylglutaminic acid hydrochloride derivative neuroglutam (glutaron), exhibiting antidepressant and anxiolytic activity upon intragastric administration in doses of 26, 130 and 650 mg/kg to female rats from 6 to 16 days of pregnancy, does not impair organo- and fetogenesis processes (developments of fetus) registered during the anthenatal period, decreases fetal death, and activates the processes of prenatal development of the fetus bv 11.1% (p < 0.001), 8.3% (p < 0.001), and 2.8% (p < 0.05), respectively.

Effects of Impaza on the Generative Function of Female Rats.

The effects of impaza on ovulatory cycles, sexual behavior, and conception processes were studied in female rats. A two-week course of impaza in doses of 3 and 15 ml/kg did not affect alternation of estrous cycle phases, the incidence of estrus reducing. Sexual behavior of these females was characterized by activation of the receptive sexual motivations; conception was characterized by a higher fertility index and a lower fetal mortality.

Effects of a New Benzimidazole Derivative on Generative Function of Female Rats.

The effects of a new thietanylbenzimidazole derivative (K-134) on estrous cycles, conception processes, and sexual behavior of female rats were studied. Two-week oral treatment with K-134 in doses of 5 and 50 mg/kg shortened the estrus phase and prolonged proestrus. Changes in sexual behavior were presented by activation of receptive sexual motivations without affecting proceptive motivations. The pregnancy and fertility indexes in experimental females after mating with intact males increased and pre- and postimplantation embryonic death decreased.

Experimental study of the efficiency of Dietressa preparation on body weight reduction in mice feeding high-fat ration.

We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male mice feeding standard high-fat ration (24%). After 5-month daily intragastric administration of Dietressa, body weight gain was the lowest in comparison with other groups and did not differ from that in mice receiving the reference substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not increase motor activity of animals in the open field test and produced no anorectic effect. The mean body weight gain per each 1000 kcal of consumed food in the group of animals receiving Dietressa was lower than in the control group and mice receiving sibutramine.

Experimental study of the effects of Dietressa, a new weight-reducing drug.

The capacity of a new drug containing ultra-low doses of antibodies to cannabinoid receptor type 1 (Dietressa) to reduce body weight gain in mice on a high-calorie diet was evaluated, possible mechanisms of drug action were analyzed, and its safety (abuse potential in the reaction of self-stimulation) was evaluated. Dietressa was not inferior to sibutramine in reducing body weight gain in mice and exhibited no abuse potential.

[Effect of ladasten on antenatal and postnatal development].

Positive effects of ladasten on both antenatal and postnatal development have been established in experiments on pregnant female rats. Under the action of this drug, the number of resorption events decreases and process of antenatal development of fetuses is activated. In the postnatal period, increased weight gain and accelerated physical development has been observed in the progeny of rats treated with ladasten.

[Effect of kardostin on the generative function of female rats].

The effects of kardostin on the ovulatory cycle, conception, and sexual behavior of female rats have been experimentally studied. It is established that a two-week therapy with kardostin at a dose of 5 and 15 mg/kg changed phases of the estrous cycle (with the estrus phase being most prevalent) and led to ambiguous changes in the sexual behavior of female rats (a dose of 5 mg/kg increased sexual behavior, while a dose of 15 mg/kg inhibited it), activated fertility, and improved the quality of conception.

Some aspects of toxicological activity of kardosten after chronic 6-month administration to rats.

Chronic treatment of rats with kardosten for 6 months had a positive effect on some ECG values and behavior without disordering the hepatorenal functions. All effects of the drug observed during a course of treatment were leveled and the parameters reached the basal values within 2 weeks after drug discontinuation, this confirming its safety.

[Effect of benzimidazole derivative with hypoglycemic activity on reproduction processes in females rats].

Toxicological experiments showed that the new benzimidazole derivative with hypoglycemic action--diabenol--influences the sexual activity and processes of female fertilization. The estrous cycle, sexual activity and quality of fertilization were activated at females upon the administration of diabenol in a therapeutic dose of 5 mg/kg. It is established that the drug administration in a toxic dose of 160 mg/kg suppresses the sexual activity and, at the same time, does not affect the estrous cycle and quality of fertilization in females.

[Effect of standardized solution of brine mineral bischofit (MgCL2.6H2O) on the antenatal development of rat fetus].

A standard solution of mineral bischofit has low toxicity and produces a dose-dependent effect on the antenatal development of rat fetuses. Bischofit in a dose of 0.01 ml/kg and 0.1 ml/kg (daily requirement for magnesium ions) increased the index of fertility and the quality of embryonal development in rats. The index of fertility was reduced and fetal skeleton formation was inhibited after the administration of bischofit in a dose of 1.0 ml/kg.

[Effect of dibazol (bendazol) on the generative function in rats].

The ambiguous influence of bendazol (5 and 160 mg/kg) on the sexual behavior and spermatogenesis of rats was observed in experiments on male rats. An increase in the duration of sexual activity and a decrease of the total amount of spermatozoons were registered irrespective of the course of drug administration in a dose of 5 mg/kg. In males treated with bendazol in a dose of 160 mg/kg, the behavior varied depending on the duration of treatment: the sexual activity decreased upon a 5-day treatment and increased after a 2-month course. The index of spermatogenesis did not depend on the time of administration at 5 or 160 mg/kg, while the spermatozoon mobility was suppressed upon the short-term treatment and increased upon the log-term administration of bendazol.

[Transplacental effects of bemithyl].

The daily administration of bemithyl (20 mg/kg) from 6 th to 16 th day of pregnancy in female rats led to the decrease in fetal death after the implantation and increased fetal body weight. The treatment of pregnant rats also led to acceleration of the development of physical condition and sensomotor reflexes of progeny in the postnatal period.

[Effect of bemithyl on sexual behavior and spermatogenesis in rats].

Bemithyl produced different influence on the sexual behavior (pairing motivation) and spermatogenesis in rats, depending on the dose and duration of drug administration. A three-day administration of bemithyl (20 and 200 mg/kg, p.o.) stimulated the sexual activity and spermatogenesis in male rats irrespective of the drug dose. The chronic administration of bemithyl over a period of 60 days led to a decrease in the male sexual activity and spermatogenesis index. This behavior can be related to the drug influence on the hypothalamus/pituitary structures responsible for the male rat generative function.

[The effect of bemithyl on the onthogenesis of rats].

Female rats were treated with bemithyl (20 and 100 mg/kg) via a gastric tube during a 16-day period of lactation. It was found that the drug is transferred with breast milk to the organism of newborns, which leads to nonuniformities in their development. Among the early effects of bemithyl, most pronounced is the stimulating action upon maturation (muscle strength) and the development of sensor-locomotor reflexes; in the spectrum of long-term effects, the drug influence upon pubescence processes was manifested.