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The therapeutic efficacy of a Russian radiopharmaceutical 177 Lu-DOTA-PSMA was studied in vivo using male BALB/c nu/nu (nude) mice with prostate carcinoma 22Rv1 xenografts by tumor growth inhibition criterion. The mean tumor volumes in mice treated with 177 Lu-DOTA-PSMA were significantly lower than in animals of the control group. There were no significant differences in the values of tumor growth inhibition between the groups of animals receiving 3.7 or 7.4 MBq of 177 Lu-DOTA-PSMA., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The specific features of alcohol behavior were studied in MR and MNRA rats that exhibit an opposite reaction to emotional stress. We evaluated the effect of a dipeptide anxiolytic GB-115 (N-phenyl-hexanoyl-glycyl-L-tryptophan amide, neuropeptide cholecystokinin-4 analogue with antagonistic activity) on alcohol motivation in rats, which was formed over 12 months. High-emotionality MR rats were more sensitive to the anxiolytic effect of ethanol in the conflict situation test than low-emotionality MNRA rats. MNRA rats consumed a greater amount of ethanol under a free-choice condition with 15% ethanol solution and water (as in comparison with MR rats). However, the behavior of MR rats was transformed due to a significant increase in alcohol motivation from the 5th month of long-term free access to ethanol. An anxiolytic GB-115 (0.025 mg/kg intraperitoneally for 14 days) with selective activity in high-emotionality rats was shown to reduce significantly the average daily consumption and alcohol-deprivation effect in MR rats, but did not modulate ethanol addiction in MNRA rats.

Angiogenic action of compound GK-2, a dimeric dipeptide mimetic of loop 4 of nerve growth factor (NGF), was studied in in vitro and in vivo experiments. Experiments on human endothelial cell culture HUVEC showed that compound GK-2 significantly (p<0.05) stimulated the initial stage of angiogenesis, and its angiogenic activity was not inferior to the reference neurotrophin NGF. In experiments with hindlimb ischemia modeled in rats, GK-2 (1 mg/kg intraperitoneally for 14 days) significantly increased the total length of capillary vessels (p<0.003) and the number of vessels per 1 mm2 ischemic tissue (p<0.001) in comparison with the control. Our findings indicate that under experimental conditions compound GK-2 exhibits not only angiogenic, but also anti-ischemic activity.

Experiments on rats showed that neurospecific protein preparations reduce the severity of neurological deficit, restore the structure of individual behavior of the animals with different hypoxia tolerance, and exert antioxidant action during chronic ischemic damage to the brain unfolding during the early and late phases of ischemic preconditioning.

The effectiveness of surgery, immunomodulator "Vilon" therapy, and their combination in the treatment of experimental endometriosis in rats was assessed by the parameters of reproductive function. The experiments demonstrated that surgery combined with intraperitoneal application of "Vilon" is a promising option in the treatment of endometriosis.

Developing diabetes was modeled on adult male Wistar rats by repeated intraperitoneal injections of streptozotocin in a subdiabetogenic dose of 30 mg/kg for 3 days. Proline-containing dipeptide drug Noopept or a standard diabetic drug dipeptidyl peptidase-4 inhibitor sitagliptin was administered per os in a dose of 5 mg/kg before each injection of the toxin and then for 16 days after streptozotocin course. In active control group, spontaneously increase glucose level and reduced tolerance to glucose load (1000 mg/kg intraperitoneally) were observed on the next day after the third administration of toxin. Basal glucose level decreased by day 16, but glucose tolerance remained impaired. Noopept normalized the basal blood glucose level and tolerance to glucose load on the next day after administration of streptozotocin. The effect of Noopept persisted to the end of the experiment. At early terms of the experiment, sitagliptin was somewhat superior to Noopept by the effect on baseline glucose level, but was inferior by the influence on glucose tolerance.. By the end of the experiment, Noopept significantly (by 2 times) surpassed sitagliptin by its effect on glucose tolerance.

The protective effects of a new low-molecular-weight mimetic of nerve growth factor hexamethylene diamide bis-(N-monosuccinyl-L-glutamine-L-lysine; GK-2) were studied on the experimental model of hemorrhagic stroke (intracerebral posttraumatic hematoma) in rats. Intraperitoneal injections of GK-2 in a dose of 1 mg/kg 4 and 24 h after surgery and 24 h before testing the CNS function on days 3, 7, and 14 prevent death of experimental animals, reduce the neurological deficit, and normalized behavior.

We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed.

We studied the effect of dipeptide GB-115, a retroanalogue of cholecystokinin-4 with anxiolytic properties, on the behavior of outbred rats and BALB/c and C57Bl/6 mice induced by cholecystokinin-4 receptor agonists and yohimbine. Anxiogenic agents were shown to cause anxiety in rats and C57Bl/6 mice (with an active response to stress) in the open field test and elevated plus maze test, but did not modulate the behavior of BALB/c mice exhibiting a freezing response to emotiogenic exposure. Activation of cholecystokinin-4 type 2 receptors abolished the antianxiety effect of GB-115 in BALB/c mice. This dipeptide prevented the development of cholecystokinin-4-induced anxiety in C57Bl/6 mice and outbred rats. α(2)-Adrenoceptor antagonist yohimbine did not modulate the effects of GB-115 in BALB/c mice. GB-115 did not prevent the development of yohimbine-induced anxiety in C57Bl/6 mice. Our results confirm the data on phenotype-specific activity of GB-115. We conclude that cholecystokinin-4 and GB-115 have a common pharmacological target.

The study examined the antinociceptive potency of dipeptide compound GB-115 (amide N-6-phenylhexanoyl-glycyl-L-tryptophan) during thermal and chemical noxious stimulation of mice. Peroral administration of GB-115 (0.1-20 mg/kg) decreased the incidence of abdominal contractions induced with intraperitoneal acetic acid (0.75%). This effect was comparable to that of sodium diclofenac (20 mg/kg); it was only partially antagonized with naloxone indicating the presence of significant non-opioid component in analgesic effect of GB-115. Ability of this dipeptide to moderate the nociceptive response in tail flick test under a non-selective blockade of the opioid receptors with naloxone and the absence of similar analgesic potency assessed in the hot plate test attest to predominant effect of GB-115 on spinal opioid receptors.

An intraperitoneal injection of GK-2 (dipeptide mimetic of nerve growth factor, 0.01-5.00 mg/kg) 24 h before the adverse exposure reduced the severity of haloperidol-induced catalepsy in rats. This agent retained the activity after oral administration in a dose of 10 mg/kg. An intraperitoneal injection of GK-2 in a dose of 1 mg/kg reduced the severity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome in mice. Administration of GK-2 45 min after haloperidol treatment was also followed by a decrease in the degree of catalepsy. The repeated intraperitoneal treatment with GK-2 in a dose of 1 mg/kg after intrastriatal injection of 6-hydroxydopamine was shown to prevent the development of apomorphine-induced rotations in rats.

Magnetic resonance tomography, staining with triphenyltetrazolium chloride, and tests for evaluation of functional disturbances "cylinder" and "limb stimulation" showed that daily intraperitoneal injection of dipeptide mimetic of nerve growth factor GK-2 (1 mg/kg) for 6 days to rats with experimental focal ischemia provoked by unilateral intravascular occlusion of a branch of the middle cerebral artery significantly improved neurological deficit and decreased the infarction area.

Experiments on adult Wistar rats showed that injection of beta-amyloid25-35 (2 microg) into Meynert basal nuclei caused long-term memory deficiency which was detected 24 days after this injection by the memory trace retrieval in conditioned passive avoidance reflex (CPAR). The effects of noopept, an original nootropic and neuroprotective dipeptide, on the severity of this cognitive deficiency were studied. Preventive (for 7 days before the injury) intraperitoneal injections of noopept in a dose of 0.5 mg/kg completely prevented mnestic disorders under conditions of this model. Noopept exhibited a significant normalizing effect, if the treatment was started 15 days after the injury, when neurodegenerative changes in the basal nuclei, cortex, and hippocampus were still acutely pronounced. The mechanisms of this effect of the drug are studied, including, in addition to the choline-positive effect, its multicomponent neuroprotective effect and stimulation of production of antibodies to beta-amyloid25-35. Noopept efficiency in many models of Alzheimer disease, its high bioavailability and low toxicity suggest this dipeptide for further studies as a potential agent for the treatment of this condition (initial and moderate phases).

Experiments on outbred albino male rats showed that psychoemotional stress induced by intraperitoneal injection of cholecystokinin-4 (100 microg/kg) increased anxiety, impaired orientation and exploration activities in the elevated plus-maze and hole-board tests, and increased the level of depression of Porsolt test. Preliminary intranasal administration of glyprolines (15 min before cholecystokinin) in a dose of 3.7 micromol/kg prevented the development of stress-induced behavioral disturbances. Administration of peptides 30 min after cholecystokinin-4, i.e., to rats with developed behavioral disturbances, almost completely abolished these disturbances.

Experiments on male outbred albino rats showed that stress (10-min swimming) increased anxiety and inhibited orientation and exploratory activities. Poststress (15 min after the end of swimming) intranasal administration of peptides Pro-Gly-Pro and Gly-Pro in a dose of 3.7 micromol/kg prevented stress-induced behavioral disorders. This effect persisted for 3 h.

Long-lasting effects of new Russian psychotropic drugs Noopept and Afobazol on active avoidance conditioning and formation of learned helplessness neurosis were studied on an original experimental model in rats. Noopept eliminated the manifestations of learned helplessness after long-term (21-day) treatment by increasing the percent of trained animals. Afobazol was low effective in preventing manifestations of learned helplessness, but if used for a long time, it reduced the incidence of learned helplessness development by increasing the percent of untrained animals.

We studied the effect of Vilon in rats 2, 4, and 6 months after the onset of chronic renal failure. Subcutaneous injection of Vilon significantly decreased serum concentration of transforming growth factor-beta(1) and permeability of mesenteric microvessels in rats 2 months after the onset of chronic renal failure. Our results indicate that the preparation produces a potent homeostatic effect in the early period of chronic renal failure.

We studied the effects of new psychotropic preparations noopept and afobazole on acquisition of the conditioned active avoidance response and development of neurosis of learned helplessness in rats. Noopept in doses of 0.05-0.10 mg/kg accelerated acquisition of conditioned active avoidance response and reduced the incidence of learned helplessness in rats. Afobazole in a dose of 5 mg/kg produced an opposite effect, which is probably related to high selective anxiolytic activity of this preparation.

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Female transgenic FVB mice carrying breast cancer gene HER-2/neu were monthly injected with Vilon or Epithalon (1 microgram subcutaneously for 5 consecutive days) starting from the 2nd month of life. Epithalon markedly inhibited neoplasm development: the maximum size of breast adenocarcinomas was 33% lower than in the control (p < 0.05). The intensity of HER-2/neu mRNA expression in breast tumors of Epithalon-treated mice was 3.7 times lower than in control animals. These results indicate that Epithalon inhibits breast tumor development in transgenic mice, which is probably related to suppression of HER-2/neu expression.

The effect of peptide vilon (Lys-Glu) on urinary bladder carcinogenesis in rats was studied. Urinary bladder tumors were induced with a selective carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. The tumors developed in 56% vilon-treated animals and in 75.5% controls. Vilon 2-fold decreased the incidence of preneoplastic and early neoplastic changes in urinary bladder mucosa and significantly inhibited carcinogenesis.

Antiamnestic effect of acyl-prolyl-containing dipeptide GVS-111 was demonstrated in rats with bilateral compression-induced damage to the frontal cortex. Both intraperitoneal and oral administration of the dipeptide improved retrieval of passive avoidance responses in rats with compression-induced cerebral ischemia compared to untreated controls.