Reviews on Clinical Pharmacology and Drug Therapy
Quarterly peer-review medical journal published since 2002.
Editor-in-Chief
- Petr D. Shabanov, MD, Dr. Science (Medicine), professor, Head of Pharmacology Department of S.M. Kirov Military Medical Academy
ORCID iD: 0000-0003-1464-1127
Publisher and founder
- Eco-Vector
WEB: eco-vector.com
About
The journal publishes scientific reviews and original articles in Russian and English on clinical, clinical-experimental and fundamental research, lectures for doctors on current sections of pharmacology and the history of medicine, as well as auxiliary materials on all current issues of basic and clinical pharmacology, drug therapy and related disciplines.
The main topics of the journal are focused on key issues of fundamental and clinical pharmacology, especially molecular, genetic and translational aspects of pharmacological science.The journal is the sole peer-reviewed medical journal in Russia that specialized on high evidence level reviews publication only. The published articles constitute the scientific evidence base, which the healthcare system’s policy on the use of medicines relies on.
The journal publishes different types of reviews on modern approaches to pharmacotherapy for a wide range of diseases. The journal publishes reviews of research involving not only humans but also experimental animal models of human disease.
The journal is aimed for healthcare professionals, academic reasearchers and lecturers of medical universities: researchers, pharmacologists, pharmacists, physiologists, biochemists, as well as specialists in all related areas of internal medicine, including interns, postgraduate students and students of medical universities.
The mission of the journal:
- To integrate the results of scientific works of Russian-speaking scientists and the rich clinical experience of doctors in the development and use of drugs of various groups into the international scientific space, to be an international scientific platform for discussion and exchange of experience of doctors and scientists in the field of clinical pharmacology and drug therapy.
- To provide healthcare professionals, university lecturers and academic scientists with relevant and high-quality scientific information about the most modern and effective drugs in Russian and English.
Indexation
Manuscript submission
- English, Russian, Chineese
- ASC (Article Submission Charge)
- Online manuscript submission only
Articles distribution
- Hibrid model for an access to articles (Subscription and/or Open Access with CC BY-NC-ND)
- Free full open access for Published Ahead-of-Print (Online First) articles
- Publications in English full-text for all the articles irrespective of a manuscript language
- Free of Charge subscription for all the authors of the journal
- Free of Charge subscription for regular peer-reviewers
Announcements More Announcements...
![]() 'Reviews on Clinical Pharmacology and Drug Therapy' journal accepted for indexing in SCOPUSPosted: 20.07.2023
The 'Reviews on Clinical Pharmacology and Drug Therapy' journal has been successfully evaluated and accepted for indexing in the SCOPUS database. The Scopus Content Selection & Advisory Board (CSAB) has reviewed the journal and approved it for coverage. The message from CSAB was received on 11.07.2023. Journal evaluation tracking URL: https://suggestor.step.scopus.com/progressTracker/?trackingID=0544394189A9AFC1 All articles published in the journal from 2023 are subject for indexation. |
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Vol 22, No 2 (2024)
- Year: 2024
- Published: 22.07.2024
- Articles: 9
- URL: https://journals.eco-vector.com/RCF/issue/view/9044
- DOI: https://doi.org/10.17816/RCF.222
Reviews
Modern view on the effectiveness and safety of non-steroidal anti-inflammatory drugs
Abstract
Issues of the effectiveness and safety of drugs remain relevant and controversial. The benefits and risks of drug therapy are two facets of one whole, called pharmacotherapy, which can have undesirable side and even negatively outweigh the benefits. The effectiveness and safety of drugs must be studied comprehensively because new effects of drugs may be discovered and new mechanisms for unregistered indications may be revealed. Moreover, a deep understanding of adverse drug reactions will allow for the accurate prescription of drugs and proper medical supervision of therapy. Nonsteroidal anti-inflammatory drugs are over-the-counter drugs perceived by patients as safe and do not require a doctor’s prescription, which can cause dangerous drug reactions, particularly when used uncontrollably. The review presents literature data from studies on the effectiveness of nonsteroidal anti-inflammatory drugs and current data on new therapeutic effects of individual drugs, risks of adverse reactions, their mechanisms, and treatment methods.
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Targeted delivery of the domestic anticancer drug from the group of aziridine triazines (literature review)
Abstract
Currently, the targeted delivery of anticancer drugs can significantly increase the effectiveness of therapy, reduce the side effects of systemic chemotherapy, and improve the quality of patients with cancer. This review aimed to summarize data about the domestic antitumor drug 2,4-bis(1-aziridinyl)-6-(2,2-dimethyl-5-hydroxymethyl-1,3-dioxan-5-yl)amino-1,3,5-thriazine (dioxadet), its nanoforms, possibilities of its use in the clinic, and main antitumor nanodrugs clinically introduced in recent years. Library databases (eLibrary, PubMed, CyberLeninka, ResearchGate, Springer, Wiley Online Library, and Elsevier) were searched for relevant information. The literature review summarizes data on the preclinical trials of dioxadet and provides information on its nanoforms, such as nanogels, nanodiamonds, silica particles, and copolymers with lactic and caproic acids. New drug nanoforms open up opportunities to reduce drug side effects and systemic toxicity, maintain optimal therapeutic concentrations, increase the drug circulation time in the blood, and control its release. The possibility of using chemopreparation cytotoxic doses is the main advantage of new nanodrugs. To date, approximately 20 antitumor nanodrugs have been introduced in clinical practice, and some nanodrugs are undergoing preclinical trials or are in various phases of clinical trials. Thus, the development of a new effective nanoform, i.e., dioxadet, makes it possible to ensure targeted drug delivery in higher cytotoxic doses to target cells, increase selective action, and reduce cytostatic toxicity to normal cells.
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Original study articles
Influence of gel matrix on the wound healing activity of adhesive dressings filled with silver nanoparticles and humic acid applied on a rat burn model
Abstract
BACKGROUND: Thermal injuries to the skin (burns) are common household and man-made traumatic injuries in humans. In wartime, thermal injuries are additional damaging factors in combined skin lesions caused by the damaging elements of modern weapons.
AIM: This study aimed to evaluate the effectiveness of gels based on silver nanoparticles in combination with humic acid on the healing of thermal skin injuries (burn wounds) in rats.
MATERIALS AND METHODS: In the experiments on 57 white nonlinear male rats weighing 218–260 g, the wound healing effects of gels with 10% humic acid modified with nanosilver on various bases, prepared in a pharmacopoeial manner, on a grade IIIB thermal skin burn model were examined. The gel bases used in three experimental groups were as follows: sodium carboxymethylcellulose (group Ia, n = 12), polyacrylamide (group Ib, n = 12), and polyethylene glycol (group Ic, n = 12). The comparison group (group II, n = 12) received Levomekol ointment, whereas the control group (group III, n = 8) did not receive treatment. A grade III thermal burn was made on the proximal part of the back under general anesthesia using a thermal applicator with a circular-shaped flat working part with a diameter of 20 mm. Seventy-two hours after the burn, the wound was freed from scab by complete excision along the border of the intact skin, a splinting ring was applied, and the study drugs were administered. The dynamics of the changes in the burn wound were assessed on days 10, 14, 17, 21, 24, and 28 using the Universal Desktop Ruler program.
RESULTS: The average times (median) to reach 75% epithelialization of wounds in groups Ia, Ic, and II were 29.4 ± 0.2, 34 (33–34), and 33.3 ± 0.45 days, respectively, whereas in groups Ib and III, the median time to 75% epithelization was not achieved. The 28-day healing index (%/day) values were 8.6, 4.8, 6.5, 6.1, and 4.4 in groups Ia, Ib, Ic, II, and III, respectively. The dynamics of epithelialization of thermal burns were most pronounced in group Ia, where the sodium carboxymethylcellulose acted as a gel base for humic substances modified with nanosilver.
CONCLUSIONS: The results indicated that the gel added with nanosilver-modified humic substances based on sodium carboxymethylcellulose has a wound healing effect on thermal skin injuries, superior to the effect of the reference drug Levomekol in terms of the healing time of burn wounds.
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Early stress in maternal deprivation affects the expression of OX1R in the limbic system of the brain and contributes to the development of anxiety-depressive symptoms in rats
Abstract
BACKGROUND: Depressive states are becoming an increasingly common mental disorder and a serious social problem that places a heavy economic burden on society. Increasing data from preclinical and clinical studies indicate that orexins (neuropeptides, also known as hypocretins) and their receptors are involved in the pathogenesis of depression. The orexinergic system regulates disrupted functions in depressive states, such as sleep, reward system, eating behavior, stress response, and monoaminergic regulation. However, the exact role of orexins in behavioral and neurophysiological disorders in depression is still unclear.
AIM: This study aimed to examine the effect of early postnatal stress on the expression of OX1R orexin in the limbic system and the development of anxiety-depressive symptoms in rats.
MATERIALS AND METHODS: Maternal deprivation was used as a model of early postnatal stress (postpartum days 2–12). The animals were divided into the control (n = 20) and maternal deprivation (n = 20) groups. On day 90 of life, the influence of early postnatal stress on the development of anxiety-depressive symptoms in adult rats was analyzed using a package of behavioral tests, namely, raised cruciform maze, forced swimming Porsolt test, and two-bottle test. After the experiments, the animals were killed by decapitation, the brain was extracted and placed in the cold, and brain structures (hypothalamus and amygdala) were isolated, immediately frozen in liquid nitrogen, and stored at a temperature of −80°C for polymerase chain reaction analysis.
RESULTS: In the “raised cruciform maze,” the maternal deprivation group spent less time in the open arms of the maze, and the time spent in the closed sleeves increased relative to the control, which can be assessed as an increase in anxiety levels. In the Porsolt test, the maternal deprivation group had increased immobilization time relative to the control group. In the two-bottle sucrose preference test, the maternal deprivation group demonstrated a decreased preference for sucrose solution, which indicates the development of anhedonia. In the hypothalamus, the mRNA expression level of OX1R significantly decreased in the experimental group compared with that in the control group. A twofold decrease in the mRNA expression level of OX1R was also observed in the amygdala of the experimental group compared with that of the control group.
CONCLUSIONS: Early stress caused by maternal deprivation resulted in a decrease in OX1R orexin expression in the hypothalamus and amygdala and contributed to the development of anxiety-depressive symptoms in rats.
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Antidepressant effect of new coumarin derivatives
Abstract
BACKGROUND: The incidence of bipolar disorder is increasing worldwide. The search for new compounds with antidepressant activity and milder adverse drug reactions is an urgent task of modern psychopharmacology.
AIM: This study aimed to analyze the effect of new neuroactive coumarin derivatives on the level of depressive behavior and monoamine metabolism in the brain structures of rats.
MATERIALS AND METHODS: The antidepressant effects of LVM-091, LVM-099, LVM-S144, and IEM-2886 were evaluated in rats subjected to the Porsolt forced swimming test and the metabolism of monoamines in brain structures (LVM-099) using high-performance liquid chromatography.
RESULTS: LVM-091, LVM-099, LVM-S144, and IEM-2886, synthesized from coumarin, decreased the immobilization time of the experimental rats in the Porsolt forced swimming test, indicating the antidepressant effect of these substances. The administration of LVM-099 at a dose of 10 mg/kg increased the level of homovanillic acid and the homovanillic acid-to-dopamine ratio in the nucleus accumbens. LVM-099 also increased 5-hydroxyindoleacetic acid levels and the 5-hydroxyindoleacetic acid-to-serotonin ratio in the nucleus accumbens. In the amygdala, the levels of norepinephrine, dopamine, serotonin, and their metabolites did not change after LVM-099 administration.
CONCLUSIONS: New coumarin derivatives exert antidepressant effects and increase the metabolism of dopamine and serotonin in rat nucleus accumbens, which can be used in the development of new highly effective antidepressants.
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Analgesic activity of new ligands of the NMDA receptor complex
Abstract
BACKGROUND: The activation of spinal cord NMDA receptors is a key factor in the pathogenesis of acute and chronic pain. Therefore, the use of existing NMDA antagonists in analgesic schemes and the development of new compounds targeting the NMDA receptor complex are gaining attention. New ligands of the glutamate NMDA receptor complex are derivatives of imidazole-4,5-dicarboxylic acid. The conformational rigidity of the molecules of imidazole-4,5-dicarboxylic acid derivatives allows for increased selectivity of interaction and reduced side effects.
AIM: This study aimed to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex, which are derivatives of imidazole-4,5-dicarboxylic acid, in rats using the tail-flick test and the formalin test.
MATERIALS AND METHODS: The analgesic activity of the compounds was examined in a model of acute somatic (thermal) pain in the tail-flick test and model of somatic pain induced by algogens in the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, and 20 mg/kg. Мetamizole was used as the comparison drug.
RESULTS: The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds on the experimental models of acute pain at doses of 5–20 mg/kg. The tail-flick latency increased by 1.4–1.7 times in the IEM-2044 and IEM-303 groups compared with the value in the control group.
CONCLUSIONS: The analgesic activity of the tested compounds at 10–20 mg/kg doses was comparable to that of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics in this pharmacological class.
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Involvement of Bdnf, Ntrk2 and Pi3k in the mechanism of binge eating after psychogenic stressors in ontogenesis
Abstract
BACKGROUND: The study of the neurochemical mechanisms of food addiction provides experimental modeling of some of its clinical manifestations.
AIM: This study aimed to examine the effect of binge eating after maternal deprivation or after rearing in social isolation on the expression of Bdnf, Ntrk2, and Pi3k in the hypothalamus of rats.
MATERIALS AND METHODS: Animals aged 2–12 days were weaned from their mother for 10 days at 180 min, and males aged 90–100 days were used in the experiments. Another group of animals was reared in individual cages from day 21 after birth, and males aged 90–100 days were used in the experiments. To induce binge eating, the animals received a high-carbohydrate feed (chocolate spread) for 1 h every day or every third day within 30 days. Fifteen minutes before feeding, the paste was placed 5 cm within visual contact.
RESULTS: In groups with intermittent exposure to high-calorie food (the animals received pasta every third day), polymerase chain reaction analysis revealed the expression of the Bdnf, Ntrk2, and Pi3k in the hypothalamus. The expression level of Bdnf was higher in the maternal deprivation group than in the control group. The expression levels of Ntrk2 and Pi3k in rats taking a high-carbohydrate feed were higher in animals reared in isolation than in those reared in the community.
CONCLUSIONS: The results present new pathways for the synthesis of peptide drugs associated with the PI3K/AKT/mTOR signaling pathway for the correction of food addiction caused by psychogenic stress in ontogenesis.
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Kiss1 kisspeptin of bony fish and mammalian kisspeptin analogs enhance the communicative behavior of Danio rerio induced by social isolation
Abstract
BACKGROUND: Rodents are often used as a social isolation model. This study investigated the effects of social isolation on Danio rerio. These animals form groups and social hierarchies and exhibit complex social interactions similar to rodents. The expression of some brain genes of fish reared in isolation was found to be different from individuals reared in a group.
AIM: This study aimed to investigate the effect of kisspeptins on the social behavior of Danio rerio in social isolation.
MATERIALS AND METHODS: Fish were placed in 200-mL measuring cups for 48 h. After the social isolation period, bony fish kisspeptins and mammalian kisspeptin analogs were administered, and their effects were tested. The animal was placed in 1-L individual tanks for 15 min and then in the tank with a glass partition, behind which are a group of congeners. Fish were allowed to approach or swim away from the partition. Two patterns were used to assess behavior: latency time and number of swims to the partition.
RESULTS: Compared with the control group with fish kept in social isolation, reliable differences were observed: The number of swims to the partition after isolation was 1.3 times higher than that in the control group (p < 0.05). After the administration of bony fish kisspeptins Kiss1 and Kiss2, no significant changes in the number of swims to the partition were observed. Moreover, after the administration of KS6 and KS10, the number of swims to the aquarium partition increased 1.6 times (p < 0.01) and 1.8 times (p < 0.001), respectively. After the administration of the comparison drug oxytocin, the number of swims to the aquarium partition increased 1.6 times (p < 0.01) compared with that in the untreated isolated group. The latency time of swimming to the partition increased 2.4 times in the untreated isolated group compared with the control group (p < 0.001). Latency time decreased 2.3 times in the group administered with oxytocin compared with the untreated isolated group (p < 0.001). In the group administered with Kiss1, the latency time decreased 2 times (p < 0.001) compared with that in the untreated isolated group. The latency time decreased 5 times (p < 0.001) after KS10 administration and 3.4 times (p < 0.001) after KS6 administration compared with that in the untreated isolated group.
CONCLUSIONS: Thus, social isolation in Danio rerio reduces communicative behavior. Analogs of mammalian kisspeptin, such as Kiss1, of bony fish and oxytocin normalize the communicative behavior of fish after a period of social isolation to the level of the control group.
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Clinical pharmacology
Modern approach to pharmacotherapy of chronic insomnia in childhood
Abstract
Insomnia is a widespread problem in the pediatric population. The prevalence of insomnia in childhood varies from 5% to 50%. The lack of adequate therapy can lead to chronicity, impairment of cognitive and motor functions, and eventually development of cardiovascular and metabolic diseases, diabetes, and gastrointestinal and mental disorders. Thus, timely identification and treatment of childhood insomnia is important. This study aimed to summarize and systematize current information about the modern approach to pharmacotherapy of chronic insomnia in childhood. Modern and foreign randomized controlled trials over the past 10 years were analyzed. Treatment of chronic insomnia includes non-pharmacological and pharmacological approaches. Behavioral strategies are recommended as first-line treatment for childhood insomnia. The availability of different pharmacological drug groups allows for a personalized approach to treatment. However, the use of off-label drugs requires a justified prescription. The lack of large-scale clinical studies on the effectiveness, tolerability, dosing, and safety profile of drugs implies the need for further research to better understand the risks (negative side effects) and benefits of using such drugs for treating sleep disorders in children.
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