Vol 14, No 1 (2023)

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.

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.

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.

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 20^th 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.