Issues of the effectiveness and safety of drugs continue to be relevant and controversial. The benefits and risks of drug therapy are two facets of one whole, called pharmacotherapy, and can turn out to be an undesirable side and even outweigh the benefits with a large negative value. The effectiveness and safety of drugs requires serious study also because it becomes possible to discover new effects of drugs and reveal new mechanisms for unregistered indications and, at the same time, a deep understanding of adverse drug reactions will allow more correct prescribing of drugs and proper medical supervision of therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are over-the-counter drugs and are perceived by a wide range of patients as safe drugs that do not require a doctor’s prescription, which can cause dangerous drug reactions, especially when used uncontrollably. The review presents literature data from studies of the effectiveness of NSAIDs and current data on new therapeutic effects of individual drugs, as well as the risks of adverse reactions, their mechanisms and methods of correction.
{"title":"Modern view on the effectiveness and safety of non-steroidal anti-inflammatory drugs","authors":"Liliya Shamal","doi":"10.17816/rcf627091","DOIUrl":"https://doi.org/10.17816/rcf627091","url":null,"abstract":"Issues of the effectiveness and safety of drugs continue to be relevant and controversial. The benefits and risks of drug therapy are two facets of one whole, called pharmacotherapy, and can turn out to be an undesirable side and even outweigh the benefits with a large negative value. The effectiveness and safety of drugs requires serious study also because it becomes possible to discover new effects of drugs and reveal new mechanisms for unregistered indications and, at the same time, a deep understanding of adverse drug reactions will allow more correct prescribing of drugs and proper medical supervision of therapy. \u0000Nonsteroidal anti-inflammatory drugs (NSAIDs) are over-the-counter drugs and are perceived by a wide range of patients as safe drugs that do not require a doctor’s prescription, which can cause dangerous drug reactions, especially when used uncontrollably. \u0000The review presents literature data from studies of the effectiveness of NSAIDs and current data on new therapeutic effects of individual drugs, as well as the risks of adverse reactions, their mechanisms and methods of correction.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"9 37","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexey Lizunov, Edgar Sekste, Andrei Lebedev, Eugenii Bychkov, Victor Lebedev, V. Goltz, Natalia D. Nadbitova, S. Pyurveev, Natalya Evdokimova, Petr Shabanov
Aim. Study of binge eating after maternal deprivation or after rearing in social isolation on the expression of the Bdnf, Ntrk2 and Pi3k genes in the hypothalamus of rats. Methods. Animals from days 2 to 12 after birth were weaned from their mother for 10 days at 180 minutes; males aged 90-100 days were used in the experiments. Another group of animals was reared in individual cages from the 21st day after birth; males aged 90-100 days were used in the experiments. When developing binge eating, the animals received a high-carbohydrate diet (Nutella chocolate spread) for 1 hour every day or every third day within 30 days. 15 min before feeding, the paste was placed within 5 cm of reach with visual contact. Results. In groups with intermittent exposure to high-calorie food (the animals received pasta every third day), PCR analysis showed the presence of expression of the Bdnf, Ntrk2 and Pi3k genes in the hypothalamus. Expression of the Bdnf gene was higher in the group of rats after maternal deprivation compared to the control. It was also shown that the expression of the Ntrk2 and Pi3k genes on a high-carbohydrate diet was higher in rats reared in isolation compared to animals reared in the community. Conclusion. The data obtained suggest new pathways for the synthesis of pharmacological agents of a peptide nature associated with the PI3K/AKT/mTOR signaling pathway for the correction of food addiction caused by psychogenic stress in ontogenesis.
{"title":"INVOLVEMENT OF BDNF, NTRK2 AND PI3K IN THE MECHANISMS OF BINGE EATING AFTER PSYCHOGENIC STRESSORS IN ONTOGENESIS","authors":"Alexey Lizunov, Edgar Sekste, Andrei Lebedev, Eugenii Bychkov, Victor Lebedev, V. Goltz, Natalia D. Nadbitova, S. Pyurveev, Natalya Evdokimova, Petr Shabanov","doi":"10.17816/rcf625676","DOIUrl":"https://doi.org/10.17816/rcf625676","url":null,"abstract":"Aim. Study of binge eating after maternal deprivation or after rearing in social isolation on the expression of the Bdnf, Ntrk2 and Pi3k genes in the hypothalamus of rats. \u0000Methods. Animals from days 2 to 12 after birth were weaned from their mother for 10 days at 180 minutes; males aged 90-100 days were used in the experiments. Another group of animals was reared in individual cages from the 21st day after birth; males aged 90-100 days were used in the experiments. When developing binge eating, the animals received a high-carbohydrate diet (Nutella chocolate spread) for 1 hour every day or every third day within 30 days. 15 min before feeding, the paste was placed within 5 cm of reach with visual contact. \u0000Results. In groups with intermittent exposure to high-calorie food (the animals received pasta every third day), PCR analysis showed the presence of expression of the Bdnf, Ntrk2 and Pi3k genes in the hypothalamus. Expression of the Bdnf gene was higher in the group of rats after maternal deprivation compared to the control. It was also shown that the expression of the Ntrk2 and Pi3k genes on a high-carbohydrate diet was higher in rats reared in isolation compared to animals reared in the community. \u0000Conclusion. The data obtained suggest new pathways for the synthesis of pharmacological agents of a peptide nature associated with the PI3K/AKT/mTOR signaling pathway for the correction of food addiction caused by psychogenic stress in ontogenesis.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ekaterina Yakovleva, Mekhriniso Kamalova, Mariia Brusina, Evgenii Bychkov, L. Piotrovskiy, Petr Shabanov
According to the Russian Society for the Study of Pain, 90% of patients seeking medical help experience pain, with 70% suffering from chronic pain [15, 16]. It should be acknowledged that the capabilities of traditional analgesic methods are limited, and the prescription of opioids is associated with an increase in complications, the development of tolerance, drug dependence, and an increase in the patient's hospital stay costs. Thus, the main directions for improving pain relief include the rational combination of analgesics with different mechanisms of action and the development of new effective and safe medicinal substances with analgesic activity. It is known that 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, as well as the development of new compounds targeting the NMDA receptor complex, is of particular interest. 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 allow for increased selectivity of interaction and reduced side effects. The aim of the study was to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex - derivatives of imidazole-4,5-dicarboxylic acid in mice using the tail-flick test and the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, 20 mg/kg. Мetamizole was used as a comparison drug. The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds in experimental models of acute pain at doses of 5-20 mg/kg. In the groups receiving IEM-2044 and IEM-303, the tail-flick latency increased by 1.4-1.7 times compared to the control group. The analgesic activity of the tested compounds at doses of 10-20 mg/kg was comparable to the analgesic activity of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics among this pharmacological class.
根据俄罗斯疼痛研究学会（Russian Society for the Study of Pain）的数据，90%的求医者都经历过疼痛，其中 70% 为慢性疼痛[15, 16]。应该承认，传统镇痛方法的能力是有限的，而且阿片类药物的处方与并发症的增加、耐受性的产生、药物依赖性以及患者住院费用的增加有关。因此，改善镇痛效果的主要方向包括合理组合具有不同作用机制的镇痛药，以及开发有效、安全且具有镇痛活性的新药物。众所周知，脊髓 NMDA 受体的激活是急性和慢性疼痛发病机制的关键因素。因此，在镇痛方案中使用现有的 NMDA 拮抗剂以及开发以 NMDA 受体复合物为靶点的新化合物尤其令人感兴趣。谷氨酸 NMDA 受体复合物的新配体是咪唑-4,5-二羧酸的衍生物。咪唑-4,5-二羧酸衍生物分子的构象刚度可提高相互作用的选择性并减少副作用。研究的目的是通过尾搔试验和福尔马林试验，研究谷氨酸 NMDA 受体复合物的新配体--咪唑-4,5-二羧酸衍生物对小鼠的镇痛效果。受试化合物（IEM-303 和 IEM-2044）的腹腔给药剂量分别为 5、10、15 和 20 毫克/千克。Мetamizole 用作对比药物。实验表明，在急性疼痛实验模型中，剂量为 5-20 毫克/千克的受试化合物具有显著的剂量依赖性镇痛效果。与对照组相比，接受 IEM-2044 和 IEM-303 治疗组的尾搔潜伏期延长了 1.4-1.7 倍。在剂量为 10-20 毫克/千克时，受试化合物的镇痛活性与甲氰咪唑的镇痛活性相当，这表明这些药物的开发前景广阔，有望在这一药理类别中进一步寻找有效、安全的镇痛药。
{"title":"INVESTIGATION OF THE ANALGESIC ACTIVITY OF NEW LIGANDS OF THE NMDA RECEPTOR COMPLEX","authors":"Ekaterina Yakovleva, Mekhriniso Kamalova, Mariia Brusina, Evgenii Bychkov, L. Piotrovskiy, Petr Shabanov","doi":"10.17816/rcf624859","DOIUrl":"https://doi.org/10.17816/rcf624859","url":null,"abstract":"According to the Russian Society for the Study of Pain, 90% of patients seeking medical help experience pain, with 70% suffering from chronic pain [15, 16]. It should be acknowledged that the capabilities of traditional analgesic methods are limited, and the prescription of opioids is associated with an increase in complications, the development of tolerance, drug dependence, and an increase in the patient's hospital stay costs. Thus, the main directions for improving pain relief include the rational combination of analgesics with different mechanisms of action and the development of new effective and safe medicinal substances with analgesic activity. It is known that 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, as well as the development of new compounds targeting the NMDA receptor complex, is of particular interest. 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 allow for increased selectivity of interaction and reduced side effects. The aim of the study was to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex - derivatives of imidazole-4,5-dicarboxylic acid in mice using the tail-flick test and the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, 20 mg/kg. Мetamizole was used as a comparison drug. The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds in experimental models of acute pain at doses of 5-20 mg/kg. In the groups receiving IEM-2044 and IEM-303, the tail-flick latency increased by 1.4-1.7 times compared to the control group. The analgesic activity of the tested compounds at doses of 10-20 mg/kg was comparable to the analgesic activity of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics among this pharmacological class.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"4 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141267557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Kachanov, Olesya Aleksandrovna Belyaeva, Alexander Nikolaevich Stukov, G. V. Tochilnikov, Andrey Vladislavovich Pavlysh, Y. Zmitrichenko, Valery Anatolievich Alexandrov, Tatiana Yurievna Semiglazova, A. M. Belyaev
At the present time targeted delivery of anticancer drugs can significantly increase the effectiveness of therapy, reduce the side effects of systemic chemotherapy and improve the quality of cancer patients treatment. The aim is summarization of 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) today, its nanoforms, possibilities of use in the clinic and the main antitumor nanodrugs clinical introduced in recent years in the world. The study was conducted with search and information (eLibrary, PubMed, CyberLeninka, ResearchGate, Springer, Wiley Online Library, Elsevier) and library databases. The literature review summarizes data on preclinical trials of Dioxadet and provides information on its developed nanoforms, such as nanogels, nanodiamonds, silica particles, copolymers with lactic and caproic acids. New drug nanoforms open up opportunities to reduce its side effects and systemic toxicity, as well as maintain optimal therapeutic concentrations, increase the circulation time of the drug in the blood and control its release. The possibility of chemopreparation cytotoxic doses using is the main advantage of the new drug nanoform. To date, about 20 antitumor nanodrugs have been introduced in clinical practice, and a number of nanodrugs are undergoing preclinical and various phases of clinical trials. Thus, the development of new effective dioxadet nanoforms makes it possible to ensure targeted drug delivery in higher cytotoxic doses to the target cell, increase of the selective action, and reduce the cytostatic toxicity towards normal cells.
{"title":"Targeted delivery of the domestic anticancer drug from the group of aziridine triazines (literature review)","authors":"D. Kachanov, Olesya Aleksandrovna Belyaeva, Alexander Nikolaevich Stukov, G. V. Tochilnikov, Andrey Vladislavovich Pavlysh, Y. Zmitrichenko, Valery Anatolievich Alexandrov, Tatiana Yurievna Semiglazova, A. M. Belyaev","doi":"10.17816/rcf625968","DOIUrl":"https://doi.org/10.17816/rcf625968","url":null,"abstract":"At the present time targeted delivery of anticancer drugs can significantly increase the effectiveness of therapy, reduce the side effects of systemic chemotherapy and improve the quality of cancer patients treatment. The aim is summarization of 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) today, its nanoforms, possibilities of use in the clinic and the main antitumor nanodrugs clinical introduced in recent years in the world. The study was conducted with search and information (eLibrary, PubMed, CyberLeninka, ResearchGate, Springer, Wiley Online Library, Elsevier) and library databases. The literature review summarizes data on preclinical trials of Dioxadet and provides information on its developed nanoforms, such as nanogels, nanodiamonds, silica particles, copolymers with lactic and caproic acids. New drug nanoforms open up opportunities to reduce its side effects and systemic toxicity, as well as maintain optimal therapeutic concentrations, increase the circulation time of the drug in the blood and control its release. The possibility of chemopreparation cytotoxic doses using is the main advantage of the new drug nanoform. To date, about 20 antitumor nanodrugs have been introduced in clinical practice, and a number of nanodrugs are undergoing preclinical and various phases of clinical trials. Thus, the development of new effective dioxadet nanoforms makes it possible to ensure targeted drug delivery in higher cytotoxic doses to the target cell, increase of the selective action, and reduce the cytostatic toxicity towards normal cells.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141267150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IM: to evaluate the therapeutic effectiveness of gels based on silver nanoparticles in combination with humic acids on healing of a thermal skin damage (burn wound) in rats. MATERIALS AND METHODS: In experiments on 57 white non-linear male rats weighing 218-260 g, the wound-healing effect of gels with a 10% composition of humic acids modified with nanosilver on various bases, prepared in a pharmacopoeial manner, was studied on a model of thermal skin burn of degree IIIB. The gel base used in 3 experimental groups was sodium salt of carboxymethylcellulose (Na-CMC, group Ia, n=12), polyacrylamide (PAAM, group Ib, n=12), polyethylene glycol (PEG, group I, n=12) . Laboratory animals in the comparison group (group II, n=12) received Levomekol ointment; in the control group (group III, n=8) no treatment was carried out. A thermal burn corresponding to degree III was applied to the proximal part of the back under general anesthesia using a thermal applicator with a flat working part in the shape of a circle with a diameter of 20 mm. 72 hours after the burn, the wound was freed from the scab by complete excision along the border with intact skin with the application of a splinting ring, after which the study drugs were applied. The dynamics of changes in the burn wound were assessed on days 10, 14, 17, 21, 24, 28 using the Universal Desktop Ruler program. RESULTS: It was found that the average time (median) for 75% epithelization of wounds in groups Ia, Ic, II was 29.4±0.2, 34 (33;34) and 33.3±0.45 days, while in Ib and III groups, the median time to 75% epithelization was not achieved. The healing index (%/day) for 28 days was 8.6, 4.8, 6.5, 6.1 and 4.4 in groups Ia, Ib, Ic, II and III, respectively. The dynamics of epithelization of thermal burns was most pronounced in group Ia, where Na-CMC acted as a gel base for humic substances modified with nanosilver. CONCLUSIONS: Based on the studies conducted, it can be concluded that the gel with the addition of nanosilver-modified humic substances based on Na-CMC has a wound-healing effect in case of thermal damage to the skin, superior to the effect of the reference drug “Levomekol” in terms of the healing time of burn wounds.
{"title":"Influence of gel matrix on wound healing activity of adhesive \u0000dressings filled with silver nanoparticles and humic acids applied for \u0000the rat burn model.","authors":"Ruslan I. Glushakov, I. V. Perminova","doi":"10.17816/rcf623329","DOIUrl":"https://doi.org/10.17816/rcf623329","url":null,"abstract":"IM: to evaluate the therapeutic effectiveness of gels based on silver nanoparticles in combination with humic acids on healing of a thermal skin damage (burn wound) in rats. \u0000MATERIALS AND METHODS: In experiments on 57 white non-linear male rats weighing 218-260 g, the wound-healing effect of gels with a 10% composition of humic acids modified with nanosilver on various bases, prepared in a pharmacopoeial manner, was studied on a model of thermal skin burn of degree IIIB. The gel base used in 3 experimental groups was sodium salt of carboxymethylcellulose (Na-CMC, group Ia, n=12), polyacrylamide (PAAM, group Ib, n=12), polyethylene glycol (PEG, group I, n=12) . Laboratory animals in the comparison group (group II, n=12) received Levomekol ointment; in the control group (group III, n=8) no treatment was carried out. A thermal burn corresponding to degree III was applied to the proximal part of the back under general anesthesia using a thermal applicator with a flat working part in the shape of a circle with a diameter of 20 mm. 72 hours after the burn, the wound was freed from the scab by complete excision along the border with intact skin with the application of a splinting ring, after which the study drugs were applied. The dynamics of changes in the burn wound were assessed on days 10, 14, 17, 21, 24, 28 using the Universal Desktop Ruler program. \u0000RESULTS: It was found that the average time (median) for 75% epithelization of wounds in groups Ia, Ic, II was 29.4±0.2, 34 (33;34) and 33.3±0.45 days, while in Ib and III groups, the median time to 75% epithelization was not achieved. The healing index (%/day) for 28 days was 8.6, 4.8, 6.5, 6.1 and 4.4 in groups Ia, Ib, Ic, II and III, respectively. The dynamics of epithelization of thermal burns was most pronounced in group Ia, where Na-CMC acted as a gel base for humic substances modified with nanosilver. \u0000CONCLUSIONS: Based on the studies conducted, it can be concluded that the gel with the addition of nanosilver-modified humic substances based on Na-CMC has a wound-healing effect in case of thermal damage to the skin, superior to the effect of the reference drug “Levomekol” in terms of the healing time of burn wounds.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Goltz, Andrey А. Lebedev, S. Eresko, M. Airapetov, S. Pyurveev, E. R. Bychkov, A. A. Bayramov, Viktor A. Lebedev, Petr D. Shabanov
Relevance. Rodents are often used as model of social isolation. In the present study, we investigated the effects of social isolation in Danio rerio. Danio rerio form groups, form social hierarchies and exhibit complex of social interactions similar to rodents. The expression of a number of brain genes of fish reared in isolation was found to be different from individuals reared in a group. The aim of the study was to investigate the effect of kisspeptins on the social behaviour of Danio rerio exposed to social isolation. Materials and Methods. Fish were placed in 200 ml individual measuring cups for 48 hours. After the social isolation period, bony fish kisspeptins and mammalian kisspeptin analogues were tested. The animal was placed in the 1L individual tank for 15 min and then placed in the tank with a glass partition, behind which there was a group of congeners. Fish were allowed to approach or swim away from the partition. Two patterns were used to assess behaviour: latent time and number of swims to the partition. The results of the research. When comparing the control group with fish kept in social isolation, reliable differences were observed: The number of swims to the aquarium partition after isolation was 1,3 times higher compared to the control group (p 0,05). Against the background of Kiss1 and Kiss2 bony fish Kisspeptin administration, no significant changes in the number of swims to the aquarium partition were observed. At the same time, after administration of KS6 and KS10, increases in the number of swims to the aquarium partition were observed in 1,6 times (p 0,01) and 1,8 times (p 0,001), respectively. After administration of the comparison drug oxytocin, a 1,6 times (p 0.01) increase in the number of swims to the aquarium partition was observed compared to isolates without administration of the drug. The latent time of swimming to the partition increased 2,4 times in isolates without drug administration compared to the control group (p 0,001). Against the background of oxytocin administration, latent time decreased 2,3 times compared to isolates without drug administration (p 0,001). After Kiss1 administration, latent time decreased respectively 2 times (p 0,001) compared to isolates without drug administration. The latent time was decreased 5 times (p 0,001) after KS10 administration and 3,4 times (p 0,001) after KS6 administration compared to isolates without drug administration. Conclusion. Thus, social isolation in Danio rerio fish reduces communicative behaviour. Analogues of mammalian kisspeptin, Kiss1 kisspeptin of bony fish and oxytocin normalise the communicative behaviour of fish after a period of social isolation to the level of the control group.
{"title":"KISS1 KISSPEPTIN OF BONY FISH AND MAMMALIAN KISSPEPTIN ANALOGUES ENHANCE COMMUNICATIVE BEHAVIOUR OF DANIO RERIO INDUCED BY SOCIAL ISOLATION","authors":"V. Goltz, Andrey А. Lebedev, S. Eresko, M. Airapetov, S. Pyurveev, E. R. Bychkov, A. A. Bayramov, Viktor A. Lebedev, Petr D. Shabanov","doi":"10.17816/rcf625892","DOIUrl":"https://doi.org/10.17816/rcf625892","url":null,"abstract":"Relevance. Rodents are often used as model of social isolation. In the present study, we investigated the effects of social isolation in Danio rerio. Danio rerio form groups, form social hierarchies and exhibit complex of social interactions similar to rodents. The expression of a number of brain genes of fish reared in isolation was found to be different from individuals reared in a group. \u0000The aim of the study was to investigate the effect of kisspeptins on the social behaviour of Danio rerio exposed to social isolation. \u0000Materials and Methods. Fish were placed in 200 ml individual measuring cups for 48 hours. After the social isolation period, bony fish kisspeptins and mammalian kisspeptin analogues were tested. The animal was placed in the 1L individual tank for 15 min and then placed in the tank with a glass partition, behind which there was a group of congeners. Fish were allowed to approach or swim away from the partition. Two patterns were used to assess behaviour: latent time and number of swims to the partition. \u0000The results of the research. When comparing the control group with fish kept in social isolation, reliable differences were observed: The number of swims to the aquarium partition after isolation was 1,3 times higher compared to the control group (p 0,05). Against the background of Kiss1 and Kiss2 bony fish Kisspeptin administration, no significant changes in the number of swims to the aquarium partition were observed. At the same time, after administration of KS6 and KS10, increases in the number of swims to the aquarium partition were observed in 1,6 times (p 0,01) and 1,8 times (p 0,001), respectively. After administration of the comparison drug oxytocin, a 1,6 times (p 0.01) increase in the number of swims to the aquarium partition was observed compared to isolates without administration of the drug. The latent time of swimming to the partition increased 2,4 times in isolates without drug administration compared to the control group (p 0,001). Against the background of oxytocin administration, latent time decreased 2,3 times compared to isolates without drug administration (p 0,001). After Kiss1 administration, latent time decreased respectively 2 times (p 0,001) compared to isolates without drug administration. The latent time was decreased 5 times (p 0,001) after KS10 administration and 3,4 times (p 0,001) after KS6 administration compared to isolates without drug administration. \u0000Conclusion. Thus, social isolation in Danio rerio fish reduces communicative behaviour. Analogues of mammalian kisspeptin, Kiss1 kisspeptin of bony fish and oxytocin normalise the communicative behaviour of fish after a period of social isolation to the level of the control group.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z. G. Tadtaeva, A. Galustyan, Alexandr E. Krivoshein, V. V. Rusanovsky, Alexandr A. Akimov, I. S. Sardaryan, N. A. Kuritcyna
Aim. 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 of the disease, impairment of the child’s cognitive and motor functions, and in the long term – the development of cardiovascular and metabolic diseases, diabetes, gastrointestinal and mental disorders. Thus, timely identification and treatment of childhood insomnia is important. The goal is to summarize and systematize current information about the modern approach to pharmacotherapy of chronic insomnia in childhood. Materials and methods: an analysis of modern and foreign publications, randomized controlled trials over the past 10 years was carried out. Results. Treatment of chronic insomnia includes non-pharmacological and pharmacological approaches. Behavioral strategies are recommended as first-line treatment for childhood insomnia. The presence of different pharmacological groups of drugs allows for a personalized approach to treatment. The use of “off-label” drugs requires justified prescription. Conclusion. The lack of large-scale clinical studies on the effectiveness, tolerability, dosing and safety profile of drugs dictates the need for further research to better understand the risks (negative side effects) and benefits of using medications for sleep disorders in children.
{"title":"Modern approach to pharmacotherapy of chronic insomnia in childhood","authors":"Z. G. Tadtaeva, A. Galustyan, Alexandr E. Krivoshein, V. V. Rusanovsky, Alexandr A. Akimov, I. S. Sardaryan, N. A. Kuritcyna","doi":"10.17816/rcf624874","DOIUrl":"https://doi.org/10.17816/rcf624874","url":null,"abstract":"Aim. 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 of the disease, impairment of the child’s cognitive and motor functions, and in the long term – the development of cardiovascular and metabolic diseases, diabetes, gastrointestinal and mental disorders. Thus, timely identification and treatment of childhood insomnia is important. \u0000The goal is to summarize and systematize current information about the modern approach to pharmacotherapy of chronic insomnia in childhood. \u0000Materials and methods: an analysis of modern and foreign publications, randomized controlled trials over the past 10 years was carried out. \u0000Results. Treatment of chronic insomnia includes non-pharmacological and pharmacological approaches. Behavioral strategies are recommended as first-line treatment for childhood insomnia. The presence of different pharmacological groups of drugs allows for a personalized approach to treatment. The use of “off-label” drugs requires justified prescription. \u0000Conclusion. The lack of large-scale clinical studies on the effectiveness, tolerability, dosing and safety profile of drugs dictates the need for further research to better understand the risks (negative side effects) and benefits of using medications for sleep disorders in children.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"76 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141268183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Pyurveev, Nikolay S. Dedanishvili, E. Sexte, Andrey А. Lebedev, Eugenii Bychkov, Petr Shabanov
BACKGROUND. Depressive states are becoming an increasingly common mental disorder, as well as a serious social problem that places a heavy economic burden on society. More and more 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 functions that are disrupted 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 observed in depression is still unclear. AIM. To study the effect of early postnatal stress on the expression of OX1R orexin in the limbic system of the brain and the development of anxiety-depressive symptoms in rats. MATERIALS AND METHODS. In the work, maternal deprivation was used as a model of early postnatal stress (from the 2nd to the 12th postpartum day). Two experimental groups were formed: control (n = 20); "maternal deprivation" (n = 20). On the 90th day of life, the influence of early postnatal stress on the development of anxiety-depressive symptoms in rats in adulthood was analyzed using a package of behavioral tests. Behavior analysis was performed using the following tests: raised cruciform maze, forced swimming Porsolt test, two-bottle test. After the experiments, the animals were killed by decapitation, the brain was extracted, placed in the cold and brain structures (hypothalamus, amygdala) were isolated, immediately frozen in liquid nitrogen and stored at a temperature of -80 C until PCR analysis was performed. RESULTS. Testing of experimental animals in the "Raised cruciform maze" showed that in a group of animals subjected to deprivation from the mother, there was a decrease in the time spent 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 the level of anxiety of animals. In the Porsolt test, the maternal deprivation group had an increased immobilization time relative to the control group of animals. In the maternal deprivation group, under the conditions of a two-bottle sucrose preference test, there was a decrease in sucrose solution preference, which indicates the development of anhedonia. In the hypothalamus, there was a statistically significant decrease in the expression of OX1R mRNA in the experimental group of animals, in contrast to the intact control group. A two-fold decrease in the level of OX1R mRNA expression in the experimental group relative to the control animals was also observed in the amygdala. CONCLUSION. Early stress of maternal deprivation causes a decrease in the expression of OX1R orexin in the hypothalamus and amygdala of the brain and contributes to the development of anxiety-depressive symptoms in rats.
{"title":"EARLY STRESS OF MATERNAL DEPRIVATION AFFECTS THE EXPRESSION OF OX1R OREXIN IN THE LIMBIC SYSTEM OF THE BRAIN AND CONTRIBUTES TO THE DEVELOPMENT OF ANXIETY-DEPRESSIVE SYMPTOMS IN RATS.","authors":"S. Pyurveev, Nikolay S. Dedanishvili, E. Sexte, Andrey А. Lebedev, Eugenii Bychkov, Petr Shabanov","doi":"10.17816/rcf622940","DOIUrl":"https://doi.org/10.17816/rcf622940","url":null,"abstract":"BACKGROUND. Depressive states are becoming an increasingly common mental disorder, as well as a serious social problem that places a heavy economic burden on society. More and more 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 functions that are disrupted 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 observed in depression is still unclear. \u0000AIM. To study the effect of early postnatal stress on the expression of OX1R orexin in the limbic system of the brain and the development of anxiety-depressive symptoms in rats. \u0000MATERIALS AND METHODS. In the work, maternal deprivation was used as a model of early postnatal stress (from the 2nd to the 12th postpartum day). Two experimental groups were formed: control (n = 20); \"maternal deprivation\" (n = 20). On the 90th day of life, the influence of early postnatal stress on the development of anxiety-depressive symptoms in rats in adulthood was analyzed using a package of behavioral tests. Behavior analysis was performed using the following tests: raised cruciform maze, forced swimming Porsolt test, two-bottle test. After the experiments, the animals were killed by decapitation, the brain was extracted, placed in the cold and brain structures (hypothalamus, amygdala) were isolated, immediately frozen in liquid nitrogen and stored at a temperature of -80 C until PCR analysis was performed. \u0000RESULTS. Testing of experimental animals in the \"Raised cruciform maze\" showed that in a group of animals subjected to deprivation from the mother, there was a decrease in the time spent 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 the level of anxiety of animals. In the Porsolt test, the maternal deprivation group had an increased immobilization time relative to the control group of animals. In the maternal deprivation group, under the conditions of a two-bottle sucrose preference test, there was a decrease in sucrose solution preference, which indicates the development of anhedonia. In the hypothalamus, there was a statistically significant decrease in the expression of OX1R mRNA in the experimental group of animals, in contrast to the intact control group. A two-fold decrease in the level of OX1R mRNA expression in the experimental group relative to the control animals was also observed in the amygdala. \u0000CONCLUSION. Early stress of maternal deprivation causes a decrease in the expression of OX1R orexin in the hypothalamus and amygdala of the brain and contributes to the development of anxiety-depressive symptoms in rats.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"4 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bakhodir B. Daliev, D.I. Klimenko, Inessa V. Karpova, Leonid V. Myznikov, E. R. Bychkov, Andrey А. Lebedev, Petr D. Shabanov
Background: The number of patients with bipolar disorders is increasing worldwide. The search for new compounds with antidepressant activity and a low level of adverse drug reactions is an urgent task of modern psychopharmacology. Aim: To study 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 effect of the drugs LVM-091, LVM-099, LVM-S144, IEM-2886 was studied in the Porsolt forced swimming test in rats and the metabolism of monoamines in brain structures (studied by LVM-099) using high-performance liquid chromatography (HPLC). Results: Drugs LVM-091, LVM-099, LVM-S144, IEM-2886, synthesized on the basis of coumarin, decreased immobilization time in the Porsolt forced swimming test. This indicates the antidepressant effect of these substances. Administration of LVM-099 at a dose of 10 mg/kg increased homovanillic acid (HVA) level and the HVA to dopamine ratio in the nucleus accumbens. LVM-099 also increased 5-hydroxyindoleacetic acid (5-HIAA) levels and the 5-HIAA to serotonin ratio in the nucleus accumbens. In the amygdala, the level of norepinephrine, dopamine, serotonin and their metabolites did not change after administration of LVM-099. Conclusion. New coumarin derivatives cause an antidepressant effect and increase the metabolism of dopamine and serotonin in the nucleus accumbens of the rat brain, which in the future can be used in the development of new highly effective antidepressants.
{"title":"ANTIDEPRESSIVE EFFECT OF NEW COUMARIN DERIVATIVES","authors":"Bakhodir B. Daliev, D.I. Klimenko, Inessa V. Karpova, Leonid V. Myznikov, E. R. Bychkov, Andrey А. Lebedev, Petr D. Shabanov","doi":"10.17816/rcf623295","DOIUrl":"https://doi.org/10.17816/rcf623295","url":null,"abstract":"Background: The number of patients with bipolar disorders is increasing worldwide. The search for new compounds with antidepressant activity and a low level of adverse drug reactions is an urgent task of modern psychopharmacology. \u0000Aim: To study the effect of new neuroactive coumarin derivatives on the level of depressive behavior and monoamine metabolism in the brain structures of rats \u0000Materials and methods: The antidepressant effect of the drugs LVM-091, LVM-099, LVM-S144, IEM-2886 was studied in the Porsolt forced swimming test in rats and the metabolism of monoamines in brain structures (studied by LVM-099) using high-performance liquid chromatography (HPLC). \u0000Results: Drugs LVM-091, LVM-099, LVM-S144, IEM-2886, synthesized on the basis of coumarin, decreased immobilization time in the Porsolt forced swimming test. This indicates the antidepressant effect of these substances. Administration of LVM-099 at a dose of 10 mg/kg increased homovanillic acid (HVA) level and the HVA to dopamine ratio in the nucleus accumbens. LVM-099 also increased 5-hydroxyindoleacetic acid (5-HIAA) levels and the 5-HIAA to serotonin ratio in the nucleus accumbens. In the amygdala, the level of norepinephrine, dopamine, serotonin and their metabolites did not change after administration of LVM-099. \u0000Conclusion. New coumarin derivatives cause an antidepressant effect and increase the metabolism of dopamine and serotonin in the nucleus accumbens of the rat brain, which in the future can be used in the development of new highly effective antidepressants.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"92 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141268049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiovascular diseases are the one of the main causes of death in the 21st century. Their rating is not expected to be decreased in the near future despite all the successes in the wide distribution and using of high-tech methods of treatment. This article is devoted to the problem of introducing fundamental recent discoveries into practical medicine as part of the development of preventive, personalized and precision medicine. The author considers not used mechanisms of endogenous adaptation, prevention and preclinical diagnosis of hypoxia-associated diseases in the clinic and concludes that introducing of a new marker of adaptation to visceral hypoxemia is perspective approach in therapy of the cardiovascular diseases.
{"title":"Problematic issues of prevention and precise control of diseases associated with hypoxia","authors":"Andrey V. Lyubimov","doi":"10.17816/rcf624289","DOIUrl":"https://doi.org/10.17816/rcf624289","url":null,"abstract":"Cardiovascular diseases are the one of the main causes of death in the 21st century. Their rating is not expected to be decreased in the near future despite all the successes in the wide distribution and using of high-tech methods of treatment. This article is devoted to the problem of introducing fundamental recent discoveries into practical medicine as part of the development of preventive, personalized and precision medicine. The author considers not used mechanisms of endogenous adaptation, prevention and preclinical diagnosis of hypoxia-associated diseases in the clinic and concludes that introducing of a new marker of adaptation to visceral hypoxemia is perspective approach in therapy of the cardiovascular diseases.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"92 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140418047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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