The effect of a new kappa-opioid agonist benzimidazole derivative (compound RU-1205) on the generative function of outbred male rats was studied after oral administration for 2 months at doses of 5 mg/kg – experimentally proven therapeutic dose (TD) and 500 mg/kg (the highest dose is 100 TD). The absence of a damaging effect of the compound RU-1205 on the motivational sexual behavior of males and the processes of spermatogenesis was established.
In experiments on adult rats, females studied the effect of a new derivative of GABA – citrocard (citrate of 4-amino-3-phenylbutanoic acid) on sexual behavior and fertility. Citrocard in doses of 50 mg/kg (experimentally proven therapeutic dose) and 700 mg/kg (dose exceeding the therapeutic 14 times) was administered intragastrically to female rats for 2 weeks. It was established that after the introduction of sexual behavior in rats of females receiving a citrocard at a dose of 50 mg/kg, the duration of sexual activity did not change relative to the control, but the ability to mate with males was clearly increased (“emotional” approaches and lordoses increased by 43,8 % (p 0.01) and 30.4 % (p 0.05)), respectively. In females treated with a citrocard at a dose of 700 mg/kg, the duration of sexual activity decreased slightly, but their receptive ability was higher than the control values (the number of lordoses indicating their readiness for mating increased by 17.4 % (p 0,05). It was also revealed that when mating with intact males in rats of females previously treated with a citrocard 2-week course, fertility processes and fertility rates increased. Relative to control, in females of the experimental groups, the pregnancy index increased, by 4.8% (p 0.05) and 33.3 % (p 0.05), respectively, in doses and fertility, by 4.2% (p 0 05) and 19.0% (p 0.05), as well as their overall fetal death rates decreased, both preimplantation and postimplantation.
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.
Studies on white outbred 3,54-month-old male rats showed that stress caused by chronic 2-month social isolation has a negative impact on reproductive function. A negative effect of long-term social isolation on the sexual behavior of male rats was revealed: a statistically significant increase in the latent period until the first emotional approach to the female, a decrease in the total time of emotional approaches, the time of anogenital sniffing of the female partner, and the number of allogrooming acts. At the same time, chronic isolation stress does not have a statistically significant effect on the total number of spermatozoa in the ejaculate of male rats, but it contributes to an increase in immobile forms, a decrease in the time of spermatozoa motility and their acid resistance compared to intact animals.
In experiments on outbred male beauty 4 months of age, the effect of the new compound ZB-16 (GPR 119 receptor agonist), with hypoglycemic activity [6], on spermatogenesis and fertilizing function was studied. Compound ZB-16 was administered intragastrically to animals of the experimental groups for 2 months (equivalent to one spermatogenesis cycle) in doses: 0,5 mg/kg (experimental therapeutic dose) and 100 mg/kg (higher dose than 200 times the therapeutic dose), the control group of males was intragastrically injected with a solvent of the compound - distilled water. It was found that under the influence of ZB-16, in males in both experimental groups, the spermatogenesis index is moderately increased (by 3,0 %, p > 0,05), the total number of spermatozoa (by 44,4 %, p > 0,05 and 19,2 %, p > 0,05, respectively, the 1st and 2nd experimental groups), the number of tubules with desquamated epithelium decreases, and the number of pathological forms of spermatozoa and the number of tubules with 12th stage of meiosis are not changed. According to the results of mating of the studied groups of males with intact females, a clear tendency towards an increase in the pregnancy index and a decrease in the post-implantation death of the embryos is revealed in the females relative to the control.
In experiments on female rats, the effect of afobazole at doses of 5 mg/kg (group 1) and 100 mg/kg (group 2) on sexual behavior and fertility was studied. It was found that in the structure of sexual behavior in rats of females treated with afobazole with a 2-week course, the duration of sexual activity and the number of lordoses decreased statistically insignificantly and dose-dependently (by 12,5 and 37,5 %, respectively), with a simultaneous tendency to increase the number emotional approaches. In addition, according to the results of fertility studies in female rats, an increase in the pregnancy index by 14,6 % (p > 0,05) was noted in both study groups, and in pregnant women, an increase in fertility, respectively, by 33,7 % (p < 0,05) and 20,4 % (p < 0,05) and a dose-dependent decrease in the total (pre- and post-implantation) fetal death by 26,4 % (p > 0,05) and 54,5 % (p < 0,05). Based on the studies, it was concluded that afobazole had a positive effect on 2-weekly administration to rats of females at doses of 5 mg/kg and 100 mg/kg on fertility processes, with a slight tendency of its deprimative effect on sexual activity.
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.
ВЛИЯНИЕ НА СПЕРМАТОГЕНЕЗ КРЫС САМЦОВ НОВОГО ПРОИЗВОДНОГО АДЕНОЗИНА С АНТИДЕПРЕССИВНОЙ АКТИВНОСТЬЮ
The two month long observation of offspring from female rats, which were getting neuroglutame in the dose of 650 mg/ kg (25-fold therapeutic dose) from the 6th to the 20th day of pregnancy, showed the absence of changes in physical development. At the same time comparison of the tested rats' offspring with the group of control ones showed effects: activation of body weight increase; surpassing of the terms of muscular strength maturation and opening of eyes, as well as formation of reflex of turning over in the free fall and cliff avoidance. Descent of testicles into the scrotum of the male rats and vagina opening of the female rats matched the physiological standard and did not differ from the control indices. According to the research results there was made a conclusion about the absence of damaging influence of neuroglutame in the dose of 650 mg/kg on the processes of organo- and fetogenesis registered in the postnatal period of the offspring's development.
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.
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.