Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i>
Introduction. A characteristic manifestation of vascular brain damage is depressive disorders that accompany both acute and chronic disorders of cerebral circulation. Depression not only reduces the patient's quality of life, but also complicates the treatment of basic vascular disease, increas...
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LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2024-03-01
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| Series: | Разработка и регистрация лекарственных средств |
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| Online Access: | https://www.pharmjournal.ru/jour/article/view/1756 |
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| author | Y. Wang N. R. Bulatova E. E. Klen G. A. Rozit I. L. Nikitina E. A. Smolyarchuk K. A. Zavadich I. D. Krylova A. V. Samorodov |
| author_facet | Y. Wang N. R. Bulatova E. E. Klen G. A. Rozit I. L. Nikitina E. A. Smolyarchuk K. A. Zavadich I. D. Krylova A. V. Samorodov |
| author_sort | Y. Wang |
| collection | DOAJ |
| description | Introduction. A characteristic manifestation of vascular brain damage is depressive disorders that accompany both acute and chronic disorders of cerebral circulation. Depression not only reduces the patient's quality of life, but also complicates the treatment of basic vascular disease, increases the risk of stroke and death. Therefore, complex therapy of vascular depression includes not only antidepressants, but also basic means to correct the consequences of disorders of cerebral blood flow, including with antiplatelet activity. In this regard, the development of a new molecule based on thietane-containing heterocycles, combining the properties of an antidepressant and an antiplatelet agent.Aim. To conduct a preclinical evaluation of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazol-4 bromide when administered to rats.Materials and methods. A study was conducted of the effect of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietan-3-yl)-1H-1,2,4-triazol-4-bromide on the hemostasis system during intravenous and intragastric administration to healthy white non-linear sexually mature male rats (n = 160). Thromboelastography was performed on a TEG 5000 device, activated with a 0.2 M solution of calcium chloride, Born aggregometry and standard clotting tests to assess the coagulation component of hemostasis.Result and discussion. The findings show that 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide with peroral administration exceeded acetylsalicylic acid by 2.8 times in terms of ED50, and by 1.8 times with intravenous way of administration accordingly. A similar effect of pentoxifylline in the intravenous route of administration was recorded at a concentration of 27.8 mg/kg versus 12.4 mg/kg of compound I. The results of a complex method to assess the state of the hemostasis system indicate a more pronounced antiaggregational effect of compound I compared with pentoxifylline and acetylsalicylic acid.Conclusion. Preclinical studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4 bromide, was demonstrated that a combination of antidepressant and antiplatelet activity, which can serve as a basis for further drug development. |
| format | Article |
| id | doaj-art-474e707379cd46b7913a96108525cdb0 |
| institution | Kabale University |
| issn | 2305-2066 2658-5049 |
| language | Russian |
| publishDate | 2024-03-01 |
| publisher | LLC Center of Pharmaceutical Analytics (LLC «CPHA») |
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| series | Разработка и регистрация лекарственных средств |
| spelling | doaj-art-474e707379cd46b7913a96108525cdb02025-08-20T03:35:00ZrusLLC Center of Pharmaceutical Analytics (LLC «CPHA»)Разработка и регистрация лекарственных средств2305-20662658-50492024-03-0113124124610.33380/2305-2066-2024-13-1-16531224Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i>Y. Wang0N. R. Bulatova1E. E. Klen2G. A. Rozit3I. L. Nikitina4E. A. Smolyarchuk5K. A. Zavadich6I. D. Krylova7A. V. Samorodov8Hangzhou Normal UniversityThe University of JordanBashkir State Medical UniversityBashkir State Medical UniversityBashkir State Medical UniversityI. M. Sechenov First MSMU of the Ministry of Health of the Russian Federation (Sechenov University)I. M. Sechenov First MSMU of the Ministry of Health of the Russian Federation (Sechenov University)Bashkir State Medical UniversityBashkir State Medical UniversityIntroduction. A characteristic manifestation of vascular brain damage is depressive disorders that accompany both acute and chronic disorders of cerebral circulation. Depression not only reduces the patient's quality of life, but also complicates the treatment of basic vascular disease, increases the risk of stroke and death. Therefore, complex therapy of vascular depression includes not only antidepressants, but also basic means to correct the consequences of disorders of cerebral blood flow, including with antiplatelet activity. In this regard, the development of a new molecule based on thietane-containing heterocycles, combining the properties of an antidepressant and an antiplatelet agent.Aim. To conduct a preclinical evaluation of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazol-4 bromide when administered to rats.Materials and methods. A study was conducted of the effect of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietan-3-yl)-1H-1,2,4-triazol-4-bromide on the hemostasis system during intravenous and intragastric administration to healthy white non-linear sexually mature male rats (n = 160). Thromboelastography was performed on a TEG 5000 device, activated with a 0.2 M solution of calcium chloride, Born aggregometry and standard clotting tests to assess the coagulation component of hemostasis.Result and discussion. The findings show that 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide with peroral administration exceeded acetylsalicylic acid by 2.8 times in terms of ED50, and by 1.8 times with intravenous way of administration accordingly. A similar effect of pentoxifylline in the intravenous route of administration was recorded at a concentration of 27.8 mg/kg versus 12.4 mg/kg of compound I. The results of a complex method to assess the state of the hemostasis system indicate a more pronounced antiaggregational effect of compound I compared with pentoxifylline and acetylsalicylic acid.Conclusion. Preclinical studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4 bromide, was demonstrated that a combination of antidepressant and antiplatelet activity, which can serve as a basis for further drug development.https://www.pharmjournal.ru/jour/article/view/1756derivatives of 3-substituted thietanesantiaggregational activity |
| spellingShingle | Y. Wang N. R. Bulatova E. E. Klen G. A. Rozit I. L. Nikitina E. A. Smolyarchuk K. A. Zavadich I. D. Krylova A. V. Samorodov Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i> Разработка и регистрация лекарственных средств derivatives of 3-substituted thietanes antiaggregational activity |
| title | Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i> |
| title_full | Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i> |
| title_fullStr | Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i> |
| title_full_unstemmed | Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i> |
| title_short | Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i> |
| title_sort | results of preclinical studies of 4 2 4 nitrophenyl 2 oxoethyl 1 thietane 3 yl 1h 1 2 4 triazole 4 th bromide in relation to the hemostasis system i in vivo i |
| topic | derivatives of 3-substituted thietanes antiaggregational activity |
| url | https://www.pharmjournal.ru/jour/article/view/1756 |
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