Коррекция психоневрологических проявлений алкогольного похмелья у крыс ацетилцистеином

A significant part of patients with diabetes purchase sugar-lowering drugs (SLDs) on their own in retail pharmacy chains, and the market trends they generate represent an urgent area for this study.The aim. To study the turnover of hypoglycemic drugs, including insulins, in the commercial sector of the pharmaceutical market of the Russian Federation (RF) for 2020–2024.Materials and methods. The data presented in this article is based on a periodic retail audit conducted by the biotech company IQVIA. The period of 5 years (2020–2024) was covered. Data collection covered 33,613 commercial pharmacies in all regions of the RF (about 43% of pharmacies).Results. In the period from 2020 to 2023, a relatively stable increase in the volume of SLDs purchases was revealed, with small fluctuations, while in 2024 a significant leap in consumption was recorded, both in quantitative (packages) and in value (rubles) terms. During the entire monitoring period, the total volume of SLDs and insulin purchases in the retail market segment increased by more than 1.2 times, from 41.98 million packages in 2020 to 51.70 million in 2024. At the same time, the total procurement budget (at wholesale prices) increased by more than 2 times — from 19.40 to 41.57 billion rubles. The average price per package has also increased significantly, from 462 rubles in 2020 to 923 rubles in 2024, an increase of 1.7 times, reflecting significant inflation in the commercial pharmaceutical sector. In general, the Russian pharmaceutical market offers all variants of modern innovative hypoglycemic drugs (dipeptidyl peptidase-4 inhibitors [iDPP4], sodium-glucose cotransporter 2 inhibitors [iSGLT2], glucagon-like peptide-1 receptor agonists [arGPP-1]), which, according to general trends, demonstrate a steady increase in turnover. Older and less effective sulfonylureas and their combinations with metformin still occupy a significant market share. arGPP-1 group showed the greatest growth in quantity (11 times) and value (5 times), mainly due to the entry of Russian semaglutide analogues into the market. Government measures and investments in import substitution have led to a significant increase in the share of Russian drugs in purchases. Despite the positive dynamics of Russian production, import substitution in the SLDs segment has not achieved complete success and accounts for less than half of the turnover of hypoglycemic drugs.Conclusion. The growth of SLDs consumption in the retail segment of the RF in 2020–2024 has been revealed, especially due to the innovative drugs arGPP-1 and iNGLT2. Despite maintaining the leading position of metformin, the consumption structure is shifting towards more expensive schemes. The increase in the total procurement budget and the average package price highlights the need to expand preferential security programs. Import substitution has increased significantly over the indicated period, however, the share of domestic drugs is still less than half of the turnover.

Medical article медицинская статья

Introduction: Alcohol abuse is one of the grave social and medical problems in many countries, including Russia. Alcohol not only negatively affects health, social and family relationships, but also a person’s performance. Hangover, which is a one of the negative consequences of alcohol intake, is a complex of neurological and somatic symptoms that occur when ethanol is almost completely metabolized to acetaldehyde. This condition, despite the severity and potential economic damage, remains poorly understood, and there are no effective medicines to treat it. Aim: to provide an experimental basis for the possibility of using N-acetylcysteine (NAC), a precursor of glutathione, as a medicine for prevention of the neurological and cognitive impairments due to alcohol intoxication. Materials and Methods: The study used male Wistar rats, which were intraperitoneally injected with ethanol at a dose of 3 g/kg to simulate acute ethanol intoxication. Sixty minutes before the injection, the animals from the experimental groups were gavaged with NAC (1 g/kg) or with an equivalent volume of saline. Immediately after awakening and 3 h after it, the animals were assessed for neurological deficits, motor skills, spontaneous motor activity, and cognitive functions. After the completion of the behavioral tests, the animals were euthanized to assess the level of glutathione, triglycerides (TGs), and malonic dialdehyde (MDA) in liver homogenates, and to determine the activity of enzymatic antioxidant systems and serum aminotransferases. Results and Discussion: The ethanol intoxication in the animals from the control group was associated with pronounced signs of neurological and cognitive impairments, including low spontaneous motor and exploratory activity, impaired fine motor skills in the adhesive test, and cognitive function decline in the Morris water maze test. The rats which had received NAC before ethanol injection demonstrated better fine motor skills in the adhesive test, a higher level of spontaneous motor activity and better performance in the Morris water maze test (in comparison to the animals treated with saline before alcohol intoxication). In the animals which had received NAC, the levels of glutathione, MDA, and TGs, as well as the activity of liver antioxidant enzymes, were closer to the values of the intact rats to a greater extent than in the animals that had been injected with ethanol and received saline. Conclusion: Orally administered NAC before acute ethanol intoxication led to a decrease in the severity of neurological deficiency in rats and reduced the amnesic effect of ethanol. This could be due to an improvement of ethanol metabolism and a decrease in the severity of disorders associated with oxidative stress and liver dysfunction.

The aim of the work was to compare the effects of ademethionine, acetylcysteine and taurine on the zoosocial behavior of rats in a post-intoxicated state after an acute ethanol poisoning.Materials and methods. The study was conducted on male rats of the Wistar line. The post-intoxication state was modeled by a single injection of ethanol (3 g/kg, intraperitoneally). 30 min after awakening, the animals were injected with a physiological solution, acetylcysteine (1 g/kg), ademetionine (100 mg/kg) or taurine (40 mg/kg). A zoosocial interaction test was performed 30 min after the administration.Results. Among the behavioral indicators investigated, the following were validated: the number of acts of freezing, their duration, the number of acts of sniffing in front, the number of acts of avoidance and the number of vertical stances without support (p <0.05 between the values of the negative and positive control groups in all cases). The administration of acetylcysteine, ademetionine and taurine reduced the number of freezing acts by 53.64, 7.27 and 24.51%, respectively (p <0.05 when compared with the indicator index in the animals from the positive control group in all cases). The administration of acetylcysteine and taurine reduced the number of avoidance acts by 50 and 10%, respectively (p <0.05 when compared to that of the animals from the positive control group in both cases). All amino acids normalized the communicative performance, although it did not differ from that of the animals from the positive control group (p >0.05). Alcoholization reduced the number of vertical stances by 65% (p <0.001 when compared with that in the animals from the negative control group), and when followed by the administration of ademetionine and taurine, the reduction was 38 and 36%, respectively (p <0.05 when compared to that in the animals from the negative control group).Conclusion. According to the data obtained, sulfur-containing amino acids, primarily those that had central effects, normalized neuronal functions, positively influencing a complex behavior of rats. Taking into account the results of the previous studies, it was possible to conclude that the therapeutic effect of ademetionine and taurine in the context of a post-intoxication state is mediated by their central effects, which are not so pronounced in comparison with acetylcysteine.

The U.S. Food and Drug Administration (FDA), in particular the Center for Drug Evaluation and Research (CDER), plays a key role in ensuring the safety, efficacy, and innovation of medicines entering the U.S. market, and then the world. The annual review of new medicines approved by the FDA is an important tool for analyzing current trends in pharmacology and medicine, reflecting progress in the treatment of complex diseases, including cancers, orphan diseases, and infections. The review is compiled to familiarize medical specialists and pharmacologists with current trends in the registration of original medicines and in the therapy of malignant neoplasms, orphan diseases.The aim. To summarize and systematize data on the newest medicines that entered the market in 2024, as well as to analyze the mechanisms of their action. The article aims to inform medical specialists and pharmacologists about current trends in the development and registration of innovative medicines in 2024.Materials and methods. The presented data are taken from open sources and supplemented with the results of individual studies on new mechanisms and approaches in therapy. The main list of new drugs and introductory information about them are taken from the FDA report “Novel Drug Approvals for 2024”. Data on medicine prescriptions, as well as information on the mechanism of action, are taken from published summary of product characteristics (SmPC) published on this resource, as well as from the Drugs.com website. To describe previously registered medicines for which a new indication is presented, Drugs.com reports were also used. Structural formulas of drugs are taken from the PubChem resource. In case of the absence of structural formula, data from their SmPC or third-party resources, such as Drugbank, were used. The search for literature data on fundamental studies relating to the mechanisms of action of the presented medicines was carried out in the PubMed, ResearchGate, Google Scholar and elibrary.ru databases.Results. A statistical analysis of registrations, the dynamics of changes in the shares of various types of medicines and basic data on new original drugs registered by CDER are presented. In 2024, the FDA registered 50 original medicines, among which 48% contain a “first-in-class” molecule as an active substance. Small molecules include active substances — 60%, and biopharmaceuticals — 34% (the remaining 6% are imaging agents). At the same time, monoclonal antibodies (mAb) of antitumor and anti-inflammatory action occupy a larger share among biopharmaceuticals.Conclusion. The large proportion of biopharmaceuticals among those newly registered in 2024 emphasizes the dynamic development of the pharmaceutical industry and its focus on personalized medicine and biotechnology. Therapy based on mAbs interacting with receptors, as well as immunotherapy based on newly discovered mechanisms of antitumor immunity, occupies a separate part in the structure of registered original medicines. The search for new rational combinations of antibiotics remains relevant. Most of the original drug market is still made up of small molecules, among which there are medicines — ligands of new targets and oligonucleotide sequences.