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Vol 18, No 4 (2020)

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Strategies for search of pharmacological drugs against SARS-CoV-2 on the base of studying the structural-genetic features of coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2

Vashchenko V.I., Vilyaninov V.N., Shabanov P.D.


A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. Also the basic molecular mechanisms of an atypical pneumonia and molecular targets SARS-CoV-2 that allows to allocate 8 basic directions of search of pharmacological agents for struggle with SARS-CoV-2 are discussed. Mathematical methods of search of perspective preparations for struggle with COVID-19 are in detail discussed. The pathophysiological mechanisms of an infection inducing a lymphopenia or cytokine storm that allows to allocate a special direction of search of pharmacological preparations for struggle against new coronaviruse SARS-CoV-2 are discussed.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):269-296
pages 269-296 views

Oxidative stress as a problem of psychopharmacology

Arushanyan E.B., Naumov S.S.


The review presents current literary information about the physiological and pathophysiological aspects of oxidative stress and its participation in the development of schizophrenia and mental depression. Experimental and clinical data about its involvement in the effect of antipsychotic and antidepressant drugs are also summarized.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):297-311
pages 297-311 views

How to improve the selectivity of drugs

Dumpis M.A., Brusina M.A., Litasova E.V., Iljin V.V., Nikolayev D.N., Piotrovskiy L.B.


The review discusses in detail the causes of side effects of drugs, caused, inter alia, by the high complexity of the organism. The different ways are represented to overcome this problem by creating, in particular, targeted delivery systems. But nevertheless, drugs whose activity is manifested in milligram doses have minimal side effects.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):313-326
pages 313-326 views

Original articles

Benzodiazepine tranquilizers abolish the stress-induced increase of the brain ghrelin level in DANIO RERIO

Blazhenko A.A., Khokhlov P.P., Tissen I.Y., Devyashin A.S., Lebedev A.A., Proshin S.N., Bychkov E.R., Shabanov P.D.


Danio rerio has firmly established itself as a successful model for research in many areas of biology and medicine, first of all for developing new medicines.

The aim of our study was to evaluate ghrelin level in zebrafish brain after stress and after phenazepam usage on stressed fish.

Methods. In our study 96 Danio rerio, predator Cichlasoma nicaraguensis have been used. The fish have been kept at a normal room temperature (22–23 °C) with standard feeding time (twice per day). The level of neuropeptides has been tested by ELISA test. During experiment a fish has been firstly placed in a beaker with a dissolved pharmacological substance, then has been transferred into a tank with predator. In the end of experiment, it has been put into a novel tank for 6 min. The decapitation has been made. The brain has been divided into three anatomical parts: telencephalon just behind the olfactory bulb, the middle part – corpora bigemia and cerebellum, which is situated behind the corpora bigemia. After that the material for ELISA test was made using GhrelinFISH, MyBioSource ELISA kit.

Results. In the control group ghrelin has been determined only in the cerebellum in 57.14% of all fish. In the experiment with predator ghrelin has been found in all tested brain parts of fish, but in the telencephalon there was the highest level. In the experiment with phenazepam usage only and phenazepam administration after predator stress, the ghrelin value has not been determined at all.

Conclusion. Thus we have found out that the ghrelin value increases after predator stress and the drug phenazepam eliminated it completely after its administration. We may suppose that the administration of anxiolytics such as phenazepam can reduce the anxiety in Danio rerio.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):327-332
pages 327-332 views

Advanced method of pinealectomy in rats

Ovanesov K.B.


A description of his own modification of the method of surgical removal of the pineal gland (pinealectomy) in rats, which has a number of advantages over traditional methods, is given.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):333-334
pages 333-334 views

Clinical pharmacology

Clinical pharmacology of pyrroxane (proroxane)

Shabanov P.D.


Review of literature and own studies on the pharmacology and clinical pharmacology of the domestic α-adrenergic blocker pyrroxan (INN: proroxane). The drug was developed in the 1970s at the Institute of Toxicology of the USSR Ministry of Health (Leningrad). Expectations from α-blockers created during this period (phenoxybenzamine, phentolamine, tropafen, fepracet, dihydrogenated ergot alkaloids) were high, especially in terms of the treatment of hypertensive and ischemic conditions, however, only few drugs from this group were used in clinical practice for these purposes (prazosin, doxazosin and some others). For pyrroxan, this direction was not the main one, and it was positioned as a means of treating diencephalic disorders like vegetative crises, where the drug immediately gained popularity, and this direction of use was clearly fixed to it. In the same period, the anti-alcohol and anti-drug action of α-adrenergic blockers was found, since both in the experiment and in the clinic they demonstrated the suppression of alcohol (drug) motivation and a decrease in alcohol and drug consumption. The latter served as an impetus to the use of pyrroxane mainly in psychiatry, narcology and, to a lesser extent, in neurology, and recently the drug has been positioned almost exclusively for use in these areas of medicine. The article analyzes the current clinical use of pyrroxane.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):335-350
pages 335-350 views

Gases as ingredients of medicines

Urakov A.L.


The literature review shows that today all over the world reference books on medicines, state Pharmacopoeia, textbooks on pharmacology and pharmacy, as well as scientific articles published in pharmaceutical and pharmacological scientific journals, contain information about medicines without taking into account the presence of gases in them. The effect of each drug is historically considered on the example of the action of its main ingredient without taking into account the action of other ingredients, namely, auxiliary, formative agents and means that change the color, taste and smell of drugs. At the same time, the biological activity of the main ingredients is traditionally considered as the activity of highly purified chemical reagents with the brand “pure for analysis”. The results of a review of scientific and patent literature have shown that in natural conditions, due to high atmospheric air pressure, air gases are always present in all substances, including liquid and solid drugs, as well as human and animal body tissues. Usually, air gases remain invisible to the naked eye. It was found that the composition and quantity of gases in medicines affect their mechanical, physical, chemical and physico-chemical properties, which give the drugs a non-specific activity when applied topically. Using the example of water, solutions and tablets, it is shown how the content of gases in them changes under vacuum, low, normal and high atmospheric pressure, and how this changes their physical and chemical properties. It is shown that the regulation of the content of gases in water, solutions and tablets of medicines allows to regulate their mass, volume, specific gravity, porosity and non-specific physical and chemical activity of medicines when applied topically. It is shown that air and individual gases have biological activity, so they can determine the mechanism of action of drugs. Recipes of new medicines in which gas is an auxiliary, formative or main ingredient are given. It is proposed to include gases in the formulation of medicines, as well as to control the gas composition of medicines as an indicator of their quality and a factor of their physical and chemical activity, which can determine the type of medicines local action.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):351-358
pages 351-358 views

Preoperative antibiotic prophylaxis of odontogenic maxillary sinusitis, as a result of the formed oroantral joint

Maksimova N.V., Dulov F.V., Tkachuk M.F.


The article describes clinical research methods as an assessment of the effectiveness of preoperative antibiotic prophylaxis in operations on the alveolar process of the upper jaw.

Methods. 70 patients underwent a tooth extraction operation, complicated by perforation of the Schneider membrane in the period 2018-2019. These patients are conditionally divided into two homologous groups (body weight, gender, age, information from the medical history). Group I (34 patients) is scheduled to prescribe antimicrobial agents as preoperative antibiotic prophylaxis. In group II (36 patients), standard seven-day antibiotic therapy was performed.

Results. Infectious and inflammatory complications in group 1 occurred in 5.4% of cases, in group 2 in 6.2% of cases, the difference in the occurrence of infectious and inflammatory complications was 1.2%.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):359-363
pages 359-363 views

Short communications

Possibilities of in vivo validation of a model of experimental osteoporosis

Bairamov A.A., Mamina N.S., Karonova T.L., Shabanov P.D.


In this work, the possibilities of in vivo validation of an experimental model of osteoporosis are analyzed. The model is based on the application of biochemical methods for analyzing predictors of osteoporosis in blood serum, and their informative value in the comparative analysis of the assessment of the degree of osteoporosis based on instrumental studies of autopsy of bone tissue using atomic absorption spectroscopy and x-ray densitometry.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(4):365-367
pages 365-367 views

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