Vol 14, No 1 (2023)


Supplementing traditional drug formulation with the “needed” gases opens the way for the development of a new generation of drugs

Urakov A.L., Shabanov P.D., Gurevich K.G., Lovtsova L.V.


The mechanism of action of drugs is traditionally considered the specific action of the main active ingredients. Therefore, to study the mechanism of action of drugs, specialists use selected chemical compounds in chemically pure form. However, at the beginning of the 21st century, studies have reported that the action of drugs in dosage forms (tablets, solutions, etc.) is different from the action of chemically pure ingredients. The fact is that tablets, solutions, and other dosage forms contain not only the main ingredients but also auxiliary, shape-forming ingredients, and gases that supplement the specific action of the main ingredients with their nonspecific action. The gases penetrate the dosage forms from the air; however, selected gases can be introduced into the drugs under excessive pressure. Evidence presents that purposefully altering the gas content of drug tablets and solutions can regulate their mass, volume, specific gravity, porosity, physicochemical activity, and local pharmacokinetics and pharmacodynamics, especially when drugs are administered locally. Examples are shown on how the use of this regularity has allowed the development of a new generation of drugs in Russia, namely, drugs with a specific gas composition. Studies have reported that changing the gas composition of “old” (registered) drugs may turn them into new drugs. Some drugs invented in Russia included gases in their formulation, which play the role of auxiliary, shape-forming, and even main ingredients. Thus, the gas composition of drugs was proposed as an additional indicator of their quality and an important factor in their physicochemical activity. An expanded list of new generation drugs was hoped for in the near future.

Psychopharmacology & biological narcology. 2023;14(1):5-14
pages 5-14 views

Experimental treatment of induced fetal retardation in model animals

Bespalova O.N., Blazhenko A.A.


Intrauterine retardation is one of the major complications of pregnancy. This pathology occurs in approximately 10% of all pregnancies in developed countries and >20% in developing countries. Moreover, intrauterine retardation is more frequently associated with stillbirths than other pathologies. Despite studies conducted in the past 50 years, no generally accepted therapeutic regimen has yet been developed. Numerous drugs have been used for treatment; however, none of them has been proven effective. Moreover, after years of testing, new data are emerging about the side effects of the drugs previously used.

Various models of fetal retardation have been developed throughout the study of this problem. The main model animals are rats, pigs, and sheep. Numerous techniques and drug options have been proposed for the treatment of simulated intrauterine developmental delays in these animals. The main amino acids used for treatment were arginine, glutamine, taurine, and citrulline. Thus, the literature review aimed to analyze which model animals and experimental models of intrauterine retardation treatment most adequately reflect the effectiveness of these drugs.

Psychopharmacology & biological narcology. 2023;14(1):15-22
pages 15-22 views


Department of Pharmacology at the Imperial Medical and Surgical Academy: The first 100 years (1798–1898)

Shabanov P.D.


This article discusses the history of the creation and development of the Department of Pharmacology of the Medico-Surgical (since 1881 Military Medical) Academy for the first 100 years of its existence. The department was created in 1798 as one of the first seven departments of the academy. It taught materia medica, or medicinal substance, which then combined pharmacy, pharmacognosy, and pharmacology. The period was marked by the appearance of the first textbook on pharmacology (A.P. Nelyubin, 1827), opening of the laboratory of experimental pharmacology (O.V. Zabelin, 1868), beginning of a critical revision of the main drugs included in the state pharmacopoeia of that time, based on their experimental studies (P.P. Sushchinsky, 1876–1889), a detailed description of the principle of conditioned reflexes for studying digestive secretions (I.P. Pavlov, 1895–1897), and other significant scientific and pedagogical events. In the 19th century, the conceptual apparatus of pharmacology, its scientific methodology, was formed, which was most clearly established at the beginning of the 20th century through the efforts of N.P. Kravkov, S.V. Anichkov, and their scientific followers. However, the works performed at the Department of Pharmacology in the 19th century were not analyzed in detail by anyone; for the most part, they only mentioned the personalities of the people who headed it and their specific, primarily pedagogical successes. This article is intended to fill this gap.

Psychopharmacology & biological narcology. 2023;14(1):23-39
pages 23-39 views

Experimental Neuropharmacology

Chronobiological aspects of the anti-stress effect of anxiolytics

Ovanesov K.B., Beyer E.V., Kaminskaya O.V., Elbekyan K.S., Skornyakov A.A., Aleksanova E.M.


BACKGROUND: A stressful event, being a disturbing factor, is invariably accompanied by the disorganization of biological rhythms.

AIM: To examine the effects of stress and pharmacological substances on two models of the temporal organization of behavior, i.e., circadian locomotion and swimming dynamics in rats.

MATERIALS AND METHODS: The daily dynamics of rat mobility were assessed in a specially designed device consisting of living cells connected to a computer. Each cell is connected by a lever and a hinge with a button. When the rat moved from one end of the box to the other, the contact was closed, and the program autonomously summed up the number of such movements for each hour of the experiment. The total number of transitions was counted in 3 h, followed by the construction of a chronogram of the circadian rhythm of mobility. To assess the effect of substances on the circadian rhythm, anxiolytics diazepam (0.1 mg/kg), tofisopam (10 mg/kg), and epiphyseal hormone melatonin (0.1 mg/kg) were injected intraperitoneally into rats. Rats that received the same volume of saline injections (0.5 mL) served as controls.

RESULTS: Substances with anxiolytic properties, benzodiazepine derivatives diazepam (0.1 mg/kg) and tofisopam (10 mg/kg), and epiphyseal hormone melatonin (0.1 mg/kg), similarly eliminated stress-induced dysrhythmia in rats. Under their influence, the circadian rhythm of motor activity was normalized, and adaptive shifts were observed in the temporal dynamics of forced swimming.

CONCLUSION: A single stressful event disrupts the dynamics of daily mobility in rats. Diazepam, tofisopam, and melatonin, while differing in potency, generally alleviate these disorders. In particular, anxiolytics restore the rhythm in animals highly sensitive to stress. The studied substances reorganized the temporal dynamics in rats subjected to forced swimming and increased the proportion of long-period oscillations. Primary or secondary elimination of stress dysrhythmia is an important factor in the specific action of anxiolytics.

Psychopharmacology & biological narcology. 2023;14(1):40-48
pages 40-48 views

Monoaminergic effects of the unilateral blockade of orexin receptors (OX1R) in the enlarged amygdala under psychostimulant action

Karpova I.V., Bychkov E.R., Lebedev A.A., Shabanov P.D.


BACKGROUND: The search for new drugs potentially effective in stopping the development of pathological addictions is an urgent task of experimental psychopharmacology.

AIM: To examine the participation of brain monoaminergic systems in the mechanisms of the blocking effect of SB-408124 on the self-stimulation of the lateral hypothalamus activated with the psychostimulant β-phenylisopropylamine (PIPA) treatment.

MATERIALS AND METHODS: Male Wistar rats pre-administered with psychostimulant (PIPA, 1 mg/kg intraperitoneally) were unilaterally injected with an orexin antagonist SB-408124 (1 μg in 1 μL) into the central nucleus of the amygdala or the bed nucleus of the stria terminalis (BNST). High-performance liquid chromatography with electrochemical detection was used to determine the levels of monoamines and their metabolites: norepinephrine (NA), dopamine (DA), serotonin (5-HT), dioxyphenylacetic (DOPAC), homovaniline (HVA), and 5-hydroxyindolacetic (5-HIAA) acids on the left and right sides of the prefrontal cortex, hippocampus, striatum, and olfactory tubercle.

RESULTS: Under the action of PIPA, microinjections of SB-408124 into the right central nucleus of the amygdala induced the following effects: prefrontal cortex, an increase in the levels of HVA and 5-HT on the right side and 5-HIAA on the left; hippocampus, bilateral increase in the levels of NA and HVA and 5-HT on the right; striatum, bilateral increase in the level of DA and the left-sided increase in HVA, 5-HT, and 5-HIAA. Microinjections into the left central nucleus of the amygdala caused a right-sided decrease in NA levels, an increase in 5-HT levels, and a left-sided decrease in DA and DOPAC levels in the striatum and a left-sided increase in HVA level in the olfactory tubercle. Microinjections into the right BNST caused a left-sided decrease in the levels of NA and DA in the prefrontal cortex, bilateral decrease in DOPAC levels, a right-sided increase in 5-HT levels, and a left-sided increase in 5-HIAA levels in the striatum; and a left-sided increase in HVA levels in the olfactory tubercle. Microinjections into the left BNST caused increased 5-HT levels in the left striatum and decreased DOPAC and 5-HIAA levels in the left olfactory tubercle.

CONCLUSIONS: Right-sided microinjections cause a greater number of changes in monoamine metabolism than left-sided ones. The introduction of SB-408124 into the right structures of the enlarged amygdala increases 5-HIAA levels in the left striatum, whereas microinjections in BNST lead to increased 5-HT levels in the ipsilateral striatum and in the contralateral in the central nucleus of the amygdala

Psychopharmacology & biological narcology. 2023;14(1):48-62
pages 48-62 views

Experimental therapy for toxic pulmonary edema caused by inhalation poisoning with nitrogen oxides

Torkunov P.A., Zemlyanoy A.V., Varlashova M.B., Chepur S.V., Torkunova O.V., Shabanov P.D.


BACKGROUND: Morphological studies conducted in different phases of toxic pulmonary edema initiated by nitrogen oxides have revealed changes in blood vessels and blood cells that develop at the earliest stages of the lesion and precede edema.

AIM: To examine the cellular composition of the blood of mice in the presence of inhalation poisoning with nitrogen oxides.

MATERIALS AND METHODS: The toxic lung edema was modeled in mice by inhalation of toxic doses of nitrogen oxides LСt50. Blood cells were determined using a hematological analyzer 0.5, 3, and 24 h after poisoning. Parts of the animals, 30 min after the poisoning, were injected intraperitoneally with a complex of drugs consisting of sodium dimercaptopropane sulfonate (unithiol) 150 mg/kg, diclofenac sodium 35.0 mg/kg, and аprotinin (contrikal) 250 IU / kg.

RESULTS: In mice poisoned with nitrogen oxides, the main differences were observed in the leukocyte count, composition of the leukocyte formula, and platelet count. Thrombocytosis is observed 3 and 24 h after intoxication. The earliest manifestation of blood poisoning (0.5 h) was a decrease in the total leukocyte count (leukopenia). During the pronounced clinical manifestations of nitric oxide poisoning (3 h), a change in the leukocyte formula toward an increase in the proportion of granulocytes and “medium” cells (granulocytosis and eosinophilia-monocytosis) was noted. A day after the poisoning, the noted indicators generally return to the initial level. Treatment of poisoned animals with a combination of drugs neutralizes the observed effects.

CONCLUSION: The combination of drugs consisting of sodium dimercaptopropane sulfonate (unithiol), diclofenac sodium, and аprotinin (contrikal) was found to be effective in the treatment of toxic lung edema induced by nitrogen oxides.

Psychopharmacology & biological narcology. 2023;14(1):62-69
pages 62-69 views

A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats

Lebedev A.A., Lukashkova V.V., Pshenichnaya A.G., Bychkov E.R., Lebedev V.A., Rusanovsky V.V., Shabanov P.D.


BACKGROUND: Currently, no study has investigated on the role of ghrelin in the reinforcing system and emotional behavior. Previously, we examined the properties of GHSR1A antagonist [D-Lys3]-GHRP-6 to reduce negative emotional states caused by stress.

AIM: To study the involvement of a new peptide antagonist of the GHSR1A receptor agrelax in the control of emotional–exploratory behavior and anxiety in rats.

MATERIALS AND METHODS: Experiments were performed on 42 male Wistar rats. The behavior of rats was observed; agrelax 1 μg/mL (or water) with a volume of 20 μL (10 μl in each nostril) was administered intranasally. A battery of behavioral tests was used: an elevated plus maze, an open field, a marble test, an intruder–resident test, and an anxiety-phobic state assessment (FS).

RESULTS: In the elevated plus maze test, the time spent in the light arm and the number of hangings from the open arm increased in the test animals compared with animals that did not receive the drug (p < 0.05). After the administration of agrelax, the number of balloons buried and the number of elevations supported by the wall of the chamber in the marble test decreased compared with that in animals that did not receive the drug (p < 0.05). In the open field, agrelax-infected rats showed a decrease in the number of sniffs (p ≤ 0.01). In the FS test after the agrelax administration, the time of descent from the platform decreased compared with the control (p ≤ 0.05). In the “intruder–resident” test, individual behavior (p ≤ 0.01) and protective behavior (p ≤ 0.05) decreased after agrelax administration.

CONCLUSION: A new peptide antagonist of the GHSR1A receptor agrelax is involved in the control of emotional–exploratory behavior in rats. Agrelax reduced anxiety levels and exploratory activity. The results provide grounds for the development of new approaches to the treatment of phobic spectrum disorders using drugs that modulate ghrelin regulation.

Psychopharmacology & biological narcology. 2023;14(1):69-79
pages 69-79 views

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