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Pharmacy & Pharmacology

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Vol 13, No 1 (2025)
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https://doi.org/10.19163/2307-9266-2025-13-1

REVIEW

4-19 76
Abstract

The relationship between the influence of the brain-derived neurotrophic factor (BDNF) on the development of alcoholism and possible ways of using this molecule or related compounds (mimetics) as targets of anti-addictive action are discusses in the article.

The aim of the work was to carry out a literature review to identify potential applications of the BDNF signaling pathways to assess the feasibility of developing new drugs.

Materials and Methods. The following abstract databases were used to search for the information materials: PubMed, EMBASE, ResearchGate, elibrary.ru. The key queries for the search included the following ones: ‘BDNF’, “BDNF TrkB”, “BDNF LNGFR”, “alcoholism therapy”, “anti-addiction drugs”, “signaling pathways”, “alcoholism”, “ethanol”, “poisoning”. The depth of the search was 40 years (1985–2025). The total number of the sources included in the review is 116.

Results. This study analyzed the molecular mechanisms of the action of BDNF, including its biosynthesis, structural forms (BDNF and pro-BDNF), and functions and features of TrkB and LNGFR receptors. These receptors play a key role in the regulation of the neuronal plasticity, a neuronal survival and apoptotic processes. The performed review of the scientific literature made it possible to establish that at least 9 chemical compounds with a potential anti-addictive activity that affect the receptors and signaling cascades associated with BDNF, have been identified as of 2025. Based on the data obtained, a hypothesis about the prospective use of BDNF and its signaling pathways as potential targets for developing new pharmacological agents aimed at the treatment of alcohol dependence, have been formulated. The established facts can significantly expand the therapeutic opportunities in the fight against the alcoholic dependence and associated neurotoxic conditions.

Conclusion. At least 9 compounds with a potential anti-addictive activity associated with a mimetic effect on the receptors and signaling pathways of the BDNF molecule have been analyzed and found to exist as of 2025.

20-30 32
Abstract

The use of CDK4/6 inhibitors in the treatment of HR+/HER2 breast cancer (BC) has become increasingly widespread in recent years. When assessing the safety of CDK4/6 inhibitors, it was found that during therapy, a significant number of patients require a reduction in the initial dose of the drug due to adverse events (dose reduction), but publications summarizing such data are absent. At the same time, the time to dose reduction and its stages can significantly affect the organization of drug supply for patients with drugs of this group, having an economic and administrative effect on the healthcare system. In this regard, a review of the results of the use of CDK4/6 inhibitors presented in the literature, describing the features of dose reduction, is timely and relevant.

The aim. To conduct a literature review in order to summarize and systematize the results of the use of CDK4/6 inhibitors, describing the features of dose reduction.

Materials and methods. The literature search was carried out in the MedLine (PubMed) and Google Scholar databases from January 2016 to January 2024. The literature search was carried out using the following search queries: “ribociclib OR palbociclib OR abemaciclib” AND “breast cancer and randomized clinical trial”, “CDK4/6 inhibitors OR cyclin-dependent kinase 4/6 inhibitors” AND “metastatic breast cancer” AND “real-world” AND “dose Intensity OR dose reduction”. As a result of the search, 384 publications were found, and 15 publications were included in the final analysis. Data on dose reduction were systematized according to the following criteria: the proportion of patients who underwent the first and, if available, the second reduction, the time to dose reduction, and the intensity of dosing.

Results. Analysis of data from randomized clinical trials showed that a dose reduction was required in 31.8–57.4% of patients using CDK4/6 inhibitors. At the same time, the second dose reduction was carried out in 17.4–40% of patients. The median time to the first stage of reduction ranged from 1.2 to 3.2 months. The median relative dose intensity ranged from 66.3 to 93.0%. According to the results of the analysis of real clinical practice data, dose reduction was carried out in 28.1–59.1% of patients. At the same time, the first stage of reduction was carried out at 1–3 months of therapy, and the second at 4–17 months from the start of treatment.

Conclusion. A literature review was conducted to systematize the results of the use of CDK4/6 inhibitors, describing the features of dose reduction. Approximately up to 60% of patients need a dose reduction, regardless of the selected CDK4/6 inhibitor. Data on the frequency and time to dose reduction vary; therefore, the need for reduction in an individual patient may arise at any time, which may complicate the process of planning the provision of anti-tumor therapy drugs.

RESEARCH ARTICLE

31-44 47
Abstract

The aim. To study possible allergenic and immunotoxic properties of the recombinant non-immunogenic staphylokinase molecule with the amino acids replacement Lys74, Glu75 and Arg77 with alanine in preclinical and clinical studies.

Materials and methods. The allergenic and immunotoxic properties of the recombinant non-immunogenic staphylokinase drug were studied using standard methods in accordance with the Guidelines for the Preclinical Study of New Substances in guinea pigs (n=15) and mice (n=45) at doses 5, 10 and 20 times higher than therapeutic (for humans). A clinical study was conducted in 100 patients with acute ST-segment elevation myocardial infarction after a single intravenous injection of the drug. The study included the determination of titers of specific antibodies to recombinant non-immunogenic staphylokinase and the study of plasma neutralizing activity.

Results. During the complete set of preclinical studies, it was found that the drug does not affect the cellular and humoral immune response in guinea pigs and mice at doses many times higher than therapeutic doses for humans. It was found that the drug did not cause an immediate-type of hypersensitivity reaction (Weigle index 0) and a delayed type IV (0 points according to S.V. Suvorov) in guinea pigs, did not affect the cellular capacity of popliteal lymph nodes (reaction index 0.91), did not affect the number of nucleated and antibody-forming cells in the spleen of mice. As a result of a clinical study of recombinant non-immunogenic staphylokinase, no allergic reactions were registered. Assessment of the neutralizing activity of the plasma of patients who were administered recombinant non-immunogenic staphylokinase showed that 70% samples did not have neutralizing activity: 30% of the patients’ samples were characterized by a minimum neutralizing activity of 0.33±0.02 μg/mL, which is 30–310 times lower than after the use of native staphylokinase. These values are 7.8 times lower than the determined concentration of recombinant non-immunogenic staphylokinase  in the blood (2.59 μg/mL). Thus, the drug does not lead to the anti-staphylokinase neutralizing antibodies formation capable to neutralize its effect upon repeated administration.

Conclusion. According to the results of the trials, the absence of allergenic and immunotoxic properties of the recombinant non-immunogenic staphylokinase and its safety in relation to the immune system have been proven.

45-55 35
Abstract

The State Pharmacopoeia of the Russian Federation regulates the lower level of iodine content in Laminaria thalli. However, an excess of iodine is as harmful to the human body as its deficiency.

The aim. To determine the range of permissible iodine content in the medicinal plant raw material "Laminaria thalli" and products based on it within the framework of a risk-oriented strategy in medicine quality control.

Materials and methods. Samples of medicinal herbal preparations, biologically active additives, food products based on Laminaria thalli of various origins, samples of algae collected by the authors on the coast of the White Sea and the Pacific Ocean, as well as literature data on the iodine content in pharmacopoeial species were studied. The iodine content was determined by inductively coupled plasma mass spectrometry after extraction according to GOST EN 15111-2015. The non-carcinogenic risk was calculated in accordance with Guidance R 2.1.10.1920-04.

Results. The average (0.14%) and maximum (0.46%) iodine content in pharmacopoeial species of Laminaria thalli was determined, which correlates with the iodine content norm in Laminaria algae proposed by the U.S. Food and Drug Administration (FDA) — 0.1–0.5%. It was found that at the maximum therapeutic dose and course of treatment with laxative herbal preparations, containing 0.5% of iodine, the level of non-carcinogenic risk falls into the category of maximum permissible. Under similar conditions, treatment, for example, of mastopathy with preparations based on Laminaria thalli with 0.5% of iodine leads to an unacceptable impact of iodine on human health.

Conclusion. The authors recommend, instead of the existing norm of iodine content (not less than 0.1%), to take into account the permissible amount of this element (0.1–0.5%), which corresponds to its real content in pharmacopoeial species of Laminaria thalli.

56-66 55
Abstract

Since antiquity, еssential oils are considered as a source of bioactive molecules. Some of them have been shown to possess antiviral activities against various virus strains, among them SARS-CoV-2.

The aim of this study is the  search for compounds, among minor components extracted from different aromatic and medicinal plants collected from Algerian pharmacopeia, which may posses possible COVID-19 antiviral activities, by molecular docking in the active site of SARS-CoV-2 main protease.

Materials and methods. Thus, in this study 66 compounds which are declared at traces amount by authors in the composition of the essential oils, and selected from 9 Algerian medicinal plants were docked in the active site of SARS-CoV-2 main protease as possible inhibitors of SARS-CoV-2.

Results. The obtained result shows that only Cembrene constitutes the structure with the best affinity in the binding site of the enzyme with a Bioavailability Score “ABS” equal to 0.55 which confirm non Lipinski violations. However, the compound is predicted not orally bioavailable, because too lipophilic (lipophilicity: Log Po/w (XLOGP3)=6.04>+5.0) and less polar (polarity: TPSA=0.00Ų<20 Ų), and it is also predicted as not absorbed, not brain penetrant and not subject to active efflux from the CNS or to the gastrointestinal lumen.

Conclusion. This result deserves to be more detailed and either confirmed or invalidated with a view to better and rational exploitation.



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ISSN 2307-9266 (Print)
ISSN 2413-2241 (Online)