Vol 18, No 1 (2020)


Neurochemical mechanisms and pharmacology of ghrelins

Shabanov P.D., Lebedev A.A., Bychkov E.R., Lavrov N.V., Morozov V.I.


The purpose of the review was to analyze the neurochemical and neurophysiological mechanisms of the ghrelin system and the role of ghrelin in body functions and behavior. The focus is on the participation of ghrelin in the mechanisms of reinforcement and the formation of addictive behavior. At the beginning of the review a history of the first works on the field of ghrelin and its receptor was described. Then, genetic control, molecular precursor of ghrelin, molecular forms of ghrelin and ghrelin receptor were represented. In particular, the distribution of the ghrelin receptor, ghrelin-producing cells in the brain and its participation in various physiological functions of the body were shown. The hypothalamic functions of ghrelin were discussed: energy balance, regulation of glucose metabolism, stimulation of eating behavior, regulation of hypophys-pituitary axis (HPA) system. The connection of ghrelin with the brain CRH system was demonstrated. In particular, activation of HPA was described as a possible mechanism through which ghrelin regulates a number of physiological processes. Extrahypothalamic action of ghrelin was shown on the basis of the mechanisms of reinforcement and addiction. On the basis of their own data and literary, it was concluded that action of alcohol and psychoactive drugs are reduced after the ghrelin receptors blockade. In particular, it has been demonstrated that alcoholization of mothers affects the activity of the ghrelin system during the prenatal and early postnatal periods of development in the offspring of rats. It was shown the participation of ghrelin in memory and learning. The further perspective of the study and practical application of ghrelin-based pharmacological agents was analyzed.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):5-22
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Experimental Pharmacology

The influence of cholinergic drugs on electroencephalogram of the gonadectomized female rabbits

Kuznetsova N.N.


The results of investigation has shown, that after the gonadectomy of the rabbits-females the general power of EEG spectrum (GPS of EEG) changed under influence of cholinergic drugs. The sterilizathion of the animals leads to disorders of interaction between M- and N-cholinergic mechanisms in the brain. In particular, blockade of M-cholinoreceptors by metamizyl in intact and ovariectomized rabbits increased the GPS of EEG. The simultaneous administration of metamizyl with galantamine to intact females led to even greater increase of GPS of EEG, whereas the sterilized rabbits demonstrated its reduction. On the contrary, the application of the N-cholinoreceptors inhibitor gangleron with inhibitor of acetylcholinesterase (AChE) galantamine reduced the GPS of EEG in intact animals and increased it in gonadectomized rabbits in comparison with gangleron alone. Thus, the effect of M,N-cholinoblockators in combination with AChE inhibitor in sterilized rabbits changed the EEG spectrum to opposite in comparison with intact females.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):23-28
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Changes in the motivational component of sexual function in the offspring of rats after prenatal exposure to cholinotropic drugs

Stashina E.V., Zelener A.O., Bairamov A.A., Shabanov P.D.


Prenatal exposure to N-cholinoblocker gangleron and in lesser degree to M-cholinoblocker metamisil leads to significant violations of the motivational component of sexual function in sexually mature offspring of males, expressed in low values of primary sexual activity, and increased latency of the approach and sexual dysfunction after the acquisition of sexual experience. Among the causes of sexual dysfunction in the offspring, it can be noted a change in the hormonal background in male rats, in the form of a significant decrease in the level of the main androgen testosterone, as well as damage in the dopaminergic systems of the brain, manifested by a decrease in dopamine levels.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):29-36
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Behavioral effects of new compounds based on coumarin in rats

Kashirin A.O., Polukeev V.A., Pshenichnaya A.G., Rodionova O.M., Safonova A.F., Lebedev V.A., Lebedev A.A., Shabanov P.D.


Introduction. A study of the effects of coumarins has not received widespread use in medicine, largely due to the lack of optimal dosage forms, the creation of which is complicated by their poor solubility in water. Currently, studies are underway on the synthesis of macromolecules, combining various structural fragments, which will lead to increased biological activity of the synthesized coumarin derivatives compared to natural coumarins.

The aim of this work was to study the central effect of new coumarin-based compounds: IEM-2262, IEM-2263, IEM-2266, IEM-2267 on emotional and research behavior in rats.

Methods. Studies have been carried out using battery of tests that are commonly used to study emotional and exploratory behavior: an open field test and an elevated plus maze in rats. The neuroprotector mexidol (200 mg/kg i.p., Farmasoft, Russia) was used as a reference substance.

Results. Coumarins (10–50 mg/kg ip) have been shown to have a mild psychotropic, predominantly anti-anxiety and sedative effect. 7-Alkoxycoumarins (IEM-2262 and IEM-2266) and 4-aminocoumarins (IEM-2263 and IEM-2267) have different sensitivity in the open field compared with the effects in the elevated plus maze. Anxiolytic properties appeared in the elevated plus maze after the administration of 4-aminocoumarins (IEM-2263 and IEM-2267). The number of defecation boluses in the open field decreased as a result of the administration of 7-alkoxycoumarins (IEM-2262), which was associated not only with fear of novelty, but to a greater extent with anti-stress action. Thus, the new coumarin derivatives have mild tranquilizing and anti-stress effects and can be used in the future for post-traumatic stress disorders with panic attacks.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):37-42
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Assessment of dose-dependent effects of anxiolytics of benzodiazepine structure with diazepam as an example in Danio Rerio

Devyashin A.S., Blazhenko A.A., Lebedev V.A., Lebedev A.A., Bychkov E.R., Shabanov P.D.


Abstract. The effect of benzodiazepine anxiolytic diazepam in Danio rerio was investigated.

Methods. A stress test on novelty situation was used: a fish was placed first in a beaker with a dissolved pharmacological substance (or water) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of “freezing” of the experiment were measured.

Results. In response to the novelty of tank, the fish was shown to react by submerging to the bottom, increasing the freezing, and reducing the number of movements to the upper half of the novel tank. After diazepam exposure (administration), the fish was not only in the lower, but also in the upper part of the novel tank. A pharmacological analysis of diazepam effect in Danio rerio showed that in a certain dose range of 1–10 mg/l anxiolytic reduces (in comparison with the control group of fish) the number and time of freezing, increases the number of movements in the upper half of the tank and the swimming time in upper part of the tank. Diazepam causes a disinhibition of motor activity at doses of 1 and 5 mg/l, which may be explained by the effect of small doses of tranquilizers on presynaptic GABA-A autoreceptors. Diazepam 20 mg/l has a depriving effect.

Conclusion. Diazepam acts in a higher dose range (1–10 mg/l) than phenazepam (0.1–1 mg/l) in Danio rerio. At the same time, diazepam is characterized by a domed dose-dependent effect, in contrast to the action of phenazepam. The prospect of using Danio rerio as an animal model in behavioral pharmacology is not inferior to studies in rodents.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):43-49
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Comparative effects of antidepressants of various pharmacological groups on the behavior of adult Danio rerio

Levikin K.E., Kachanov D.A., Lapkina G.Y., Slobozhanin A.A., Pavlysh A.V.


The depressive disorders remain one of the global problems of modern society. Many issues related to this topic remain open for discussion. It is reliably known that tropical fish Danio rerio (zebrafish) are the most studied and practical model methods of preclinical studies. They have several advantages over other laboratory animals. Danio Rerio is great for modeling stress and depression in order to identify the manifestations of medication to identify the manifestations of this condition.

Methods. Danio Rerio when exposed to non-selective antidepressants and related serotonin reuptake inhibitors. Danio Rerio is under stress and depression due to acute exposure to caffeine and the subsequent use of antidepressants with timely recording and processing of the results.

Results. The effect of sertraline on the Danio rerio group in order to identify the state of stress and depression was more effective in comparison with the results obtained using amitriptyline as an antidepressant.

Conclusions. Sertraline in therapeutic concentration has a greater rate of elimination from anxiety and depression, which in turn allows us to argue about its greater effectiveness. In medical practice, it is better to prescribe drugs of the group of selective serotonin reuptake inhibitors in order to achieve a faster effect.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):51-56
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Lipid spectrum in rat offspring in a model of preconditioning of psychotraumatic effects

Klyueva N.N., Avaliani T.V., Apraksina N.K.


Psychogenic stress leads to post-traumatic stress disorders, causing gross behavioral disorders and a change in the lipid spectrum of blood serum and liver, both in individuals and their offspring. Preliminary sound loading increases the stability of rats during the experience of subsequent vital stress, which is reflected in the behavior of animals and in metabolic processes. Since preconditioning with stress music changes the state of mothers, this can affect the offspring. We have shown that stress music sessions in female rats affect the lipid parameters of their offspring. In rat pups, in comparison with the norm, the level of triglycerides in the liver tissues is increased. But the change in the lipid spectrum, both in the blood and in the liver tissues, is significantly lower than in the offspring of rats after vital stress. After sessions of stress music, rat offspring revealed gender differences: changes in lipid metabolism are more recorded in males.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):57-61
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Clinical pharmacology

Counterfeit medicines and combating in the Russian Federation

Pozhilova E.V., Novikov V.E., Guseva E.S., Savchenko A.V.


Summary. Falsification of medicines is a global problem in the modern world.

The aim of the work is to analyze the problem of falsification of drugs in the Russian pharmaceutical market and measures to counter the creation and distribution of counterfeit drugs.

Methods. Collection, systematization and analysis of modern data of scientific literature and the results of their own research on the relevant problem.

Results. The share of counterfeit pharmaceutical products in Russia can reach 12%. The most common category of counterfeit drugs on the Russian pharmaceutical market — the so-called drugs-copies. Visual distinctive features of counterfeit drugs are presented. According to the survey of pharmacy workers, 22.5% of pharmacists and pharmacists met with counterfeit drugs in their practice. The effectiveness of measures to combat counterfeit drugs in Russia is discussed. Huge hopes in this regard are placed on the track and Trance drug monitoring system.

Conclusion. The fight against drug counterfeits must be systematic and involve all stakeholders. It is necessary to identify counterfeits at all stages of promotion of medicines from the manufacturer to the consumer. It is important for drug manufacturers to disseminate information about the distinctive features of their original products. The health Ministry promptly inform the pharmacy network about detected counterfeits. Employees of pharmacies should be familiar with modern methods of detecting counterfeit. Consumers medications needed to use the capabilities of the new system of monitoring medicines Track and Trance.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):63-70
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The comparative estimation cerebroprotective activity decoctions of plants genus Caragana Lam.

Barnaulov O.D.


The ability of herbal decoctions from 17 Caragana species to prevent retrograde amnesia of the conditioned reflex of passive avoidance after maximal electroshock (MESh) was investigated. Decoctions from 8 species were effective as antiamnestic remedies. The restoration of motor components of oriental reflex losing after MESh was accelerated by 15 from 17 species according to different indices. Decoctions from C. lacta, C. arborescens were not effective in this test. Decoctions from C. grandiflora, C. pumila, C. jubata, C. microphylla, C. stenophylla, C. altaica, C. pygmaea, C. frutex, C. spinosa, C. buriatica demonstrated higher cerebroprotective activity taking into account sum of test.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):71-76
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From the history of medicine

Prominent Russian scientist Nikolai Vassilievich Lazarev (to the 125th anniversary from birth)

Vershinina S.F., Stukov A.N., Kharitonova N.N.


The paper is devoted to analysis of scientific studies of Nikolay Vassilievich Lazarev (1895-1974), the prominent Russian toxicologist and pharmacologist. The biography, his main scientific papers and personality of scientist were described. The main monographs of N.V. Lazarev finish the article.

Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):77-80
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