STUDY OF ANTISECRETORY ACTIVITY OF DINITRATE 2-PHENYL-9-DIETHYLAMINOETHYLimidazo[1,2-A] BENZIMIDAZOLE BY METHOD OF CONTINUOUS PERFUSION OF RATS’ STOMACHS


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Abstract

Nowadays, effective pharmacotherapy of acid-dependent gastrointestinal diseases remains an urgent problem of modern gastroenterology. In this regard, the search for new drugs with a pronounced antisecretory activity still continues; their aim is to keep the control over the acid production safe and effective.The aim of this study was an experimental study of the antisecretory activity of the substance and the finished dosage form (FDF) of dinitrate 2-phenyl-9-diethylaminoethylimidazo[1,2-a]benzimidazole.Materials and Methods. The study of antisecretory activity was performed by method of a continuous perfusion of rats’ stomachs. The studied substance was administered at the doses of 3, 10 and 30 mg/kg, and the FDF - at the doses of 13 and 26 mg/kg. The substance of Ranitidine (Sigma Аldrich, USA) was used as a reference object in the study of the antisecretory activity of the substance under study, and Ranitidine (Hemofarm A.D., Serbia) was used as a reference drug in the study of the FDF. In order to determine the stimulated secretion immediately before collecting the samples of the perfusate, histamine was administered subcutaneously at the dose of 5 mg/kg. The content of hydrochloric acid in the perfusate was determined by titration of a 0.01 M sodium hydroxide solution. The acidity value was determined in terms of the debit-hour of hydrochloric acid.Results and discussion. The obtained experimental data showed that the studied substance at the dose of 30 mg/kg decreased the basal hydrochloric acid secretion by 54%, which significantly exceeded the antisecretory effect of Ranitidine by 1.8 times. The FDF at the dose of 26 mg/kg, statistically reliable relative to the control and the group treated with Ranitidine, decreased the basal secretion of gastric juice by 33%. The substance at the dose of 30 mg/kg reliably suppressed the stimulated secretion of hydrochloric acid by 80%, while Ranitidine did it by 56%. The FDF at the dose of 26 mg/kg decreased the histamine-stimulated secretion by 66%, and Ranitidine did it by 52%, which was statistically reliable.Сonclusions. The studied substance and its dosage form are more effective in suppressing basal activities and exceed the anisecretory activity of H2 -histamine antagonists of Ranitidine under the conditions of the secretion stimulated by histamine.

About the authors

M. V. Chernikov

Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University

Email: pharmax@list.ru

M. A. Oganova

Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University

Email: marina-oganova81@mail.ru

A. S. Gerasimenko

Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University

Email: ger_ann5@ro.ru

E. A. Artemyev

Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University

Email: johni1001@rambler.ru

References

  1. Фундаментальные основы кислотопродукции в желудке / И.В. Маев, Д. Н. Андреев, А.В. Заборовский // Медицинский совет. - 2018. - № 3. - с. 7-14. Doi: https://doi.org/10.21518/2079-701X-2018-3-7-14
  2. Маев И.В., Самсонов А.А., Андреев Д.Н. Болезни желудка. М.: ГЭОтАР-Медиа, 2015. - 563 с.
  3. Руководство по внутренней медицине / под ред. Г.П. Арутюнова, А.И. Мартынова, А.А. Спасского. - М.: ГЭОтАР-Медиа, 2015. - 800 с.
  4. Schubert M.L. Physiologic, pathophysiologic,and pharmacologic regulation of gastric acidsecretion // Curr Opin Gastroenterol. - 2017. - 33(6). - P. 430-438. doi: 10.1097/MOG.0000000000000392.
  5. Перспективы лечения больных с кислотозависимыми заболеваниями / Кучерявый Ю.А., Андреев Д.Н. // Клинические перспективы гастроэнтерологии, гепатологии. - 2014. - № 2. - С. 15-24.
  6. Lassen A.T. Acid-related disorders and use ofantisecretory medication // Dan Med Bull. - 2007. - т. 54, №1. - P. 18-30.
  7. Дозозависимая антисекреторная активность эзомепразола: результаты длительного мониторирования внутрижелудочного рН / С.А. Курилович, Е.А. чекалина, А.В. Белковец, Л.В. Щербакова // Российский журнал гастроэнтерологии, гепатологии, колопроктологии. - 2016. - №3. - с. 33-40.
  8. НПВП-индуцированная гастропатия: от понимания механизмов развития к разработке стратегии профилактики и лечения / Г.А. Карасёва // Медицинские новости. - 2012. - № 8. - С. 21-26.
  9. Morgan D.R., Crowe S.E. Helicobacter pylori infection. In.: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management / edited by Mark Feldman, Lawrence S Friedman, Laurence J Brandt. - 10th ed. 2015: 856-884.
  10. H2-блокаторы гистаминовых рецепторов в терапевтической практике / Ж.Л. Сухих // Рецепт. - 2006. - № 1 (45). - С. 61-63.
  11. Эволюция лечения кислотозависимой патологии / С.М. ткач, А.Э. Дорофеев // Гастроэнтерология. - 2015. - №4 (58). - с. 94-100.
  12. Fandriks L. Can famotidine and omeprazole be combined on a once-daily basis? / Fandriks L., Lonroth H., Pettersson A., Vakil N // Scand. J. Gastroenterol. - 2007. - 42. - 689-694.
  13. Huang J.Q. Pharmacological and pharmacodynamic essentials of H2-receptor antagonists and proton pump inhibitors for the practising physician / Huang J.Q., Hunt R.H. // Best Pract. Res. Clin. Gastroenterol. - 2001. - 15. - 355-370.
  14. Scarpignato C. The role of H2-receptor antagonists in the era of proton pump inhibitors / Scarpignato C., Galmiche J.P. Edited by Lundell L // Guidelines for Management of Symptomatic Gastro-oesophageal Reflux Disease. - Science Press, 1998. - Р. 55-66.
  15. Современные взгляды на безопасность длительной терапии ингибиторами протонной помпы. Обзор литературы / В.А. Ахмедова, В.А. Ноздряков // РМЖ. - 2017. - №10. - с. 765-768.
  16. Modlin I.M Edkins and a century of acid suppression / Modlin I., Sachs G., Wright N., Kidd M. // Digestion. - 2005. - № 72. - С. 129-145.
  17. Salahuddin A. Benzimidazoles: A biologically active compounds / A. Salahuddin, M. Shaharyar, A. Mazumder // Arabian J. Chem. - 2017. - V. 10, Suppl. 1. - P. S157- S173. Doi: https://doi.org/10.1016/j.arabjc.2012.07.017
  18. Gaba M. Development of drugs based on imidazole and benzimidazole bioactive heterocycles: recent advances and future directions / M. Gaba, C. Mohan // Med. Chem. Res. - 2016. - № 25. - P. 173-210. Doi: https://doi. org/10.1007/s00044-015-1495-5.
  19. Yadav G., Ganguly S. Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review / G. Yadav, S. Ganguly // Eur. J. Med. Chem. - 2015. - № 97. - P. 419-443. doi: 10.1016/j.ejmech.2014.11.053.
  20. Keri R.S. Comprehensive Review in Current Developments of Benzimidazole-Based Medicinal Chemistry / R.S. Keri, A. Hiremathad, S. Budagumpi, B.M. Nagaraja // Chem. Biol. Drug. Des. - 2014. - V. 5, №2. - P. 1-47. doi: 10.1111/cbdd.12462.
  21. Липунова Г.Н. Фторсодержащие бензимидазолы и их- игетероаннелированные производные: cинтез и биологическая активность / Г.Н. Липунова, Э.В. Носова, В.Н. чарушин // Химия гетероциклических соединений. - 2014. - №6. - С. 831-859.
  22. Bansal Y. The therapeutic journey of benzimidazoles: A review / Y. Bansal, O. Silakari // Bioorganic & Medicinal Chemistry. - 2012. - № 20. - P. 6208-6236. doi: 10.1016/j. bmc.2012.09.013.
  23. Руководство по проведению доклинических исследований лекарственных средств. часть первая / под ред. А.Н. Миронов, Н.Д. Бунатян, А.Н. Васильев и др. // М.: Гриф и К, 2012. - 944 с.
  24. ГОСт Р 33044-2014. Принципы надлежащей лабораторной практики. (OECD Guide 1:1998, IDT). - М.: Стандартинформ, 2015. - 11 с.
  25. Приказ Министерства здравоохранения РФ от 1 апреля 2016 г. № 199н «Об утверждении Правил надлежащей лабораторной практики» (Зарегистрировано в Минюсте РФ 15 августа 2016 г. № 43232) // Бюллетень нормативных актов федеральных органов исполнительной власти, № 37, 12.09.16.
  26. Sherifa M. Abu-Bakr, Bassyouni F.A.; Rehim, M.A. Pharmacological evaluation of benzimidazole derivatives with potential antiviral and antitumor activity // Research on Chemical Intermediates. - 2012. - V. 38, №9. - P. 2523-2545.
  27. Keri R.S., Rajappa C.K., Patil S.A.; Nagaraja B.M. Benzimidazole-core as an antimycobacterial agent // Pharmacological Reports. - 2016. - V. 68, №6. - P. 1254- 1265. Doi: https://doi.org/10.1016/j.pharep.2016.08.002
  28. Singh N., Pandurangan A., Rana K., Anand P., Ahmad A., Tiwari A.K. Benzimidazole: A short review of their antimicrobial activities // Int. Current Pharm. J. - 2012. - V. 1, №5. - P. 119-127. Doi: https://doi.org/10.3329/icpj.v1i5.10284
  29. Shrivastava N., Naim M. J.; Alam Md. J., Nawaz F., Ahmed S., Alam O. Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure-Activity Relationship // Archiv der Pharmazie. - 2017. - V. 350, №6. doi: 10.1002/ardp.201700040
  30. Furtado L.F.V., de Paiva Bello A.C.P.; Rabelo É.M.L. Benzimidazole resistance in helminths: From problem to diagnosis // Acta Tropica. - 2016. - V. 162. - P. 95-102. doi: 10.1016/j.actatropica.2016.06.021.
  31. Gaba M., Singh S., Mohan C. Benzimidazole: an emerging scaffold for analgesic and anti- inflammatory agents // Eur. J. Med. Chem. - 2014. - V. 76. -Р. 494-505. doi: 10.1016/j. ejmech.2014.01.030.
  32. Kim R.M., Chang J., Lins A.R., Brady E., Candelore M.R., Dallas-Yang Q., Ding V. Discovery of potent, orally active benzimidazole glucagon receptor antagonists // Bioorg. Med. Chem. Lett. - 2008. - V. 18. - P. 3701. doi: 10.1016/j.bmcl.2008.05.072.
  33. Gomez H.T., Nunez E.H., Rivera I.L., Alvarez J.G., Rivera R.C. Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids // Bioorg. Med. Chem. Lett. - 2008. - V. 18. - P. 3147. doi: 10.1016/j. bmcl.2008.05.009.
  34. Ates-Alagoz Z. Antioxidant activities of retinoidal benzimidazole or indole derivatives in In vitro model systems // Current Med. Chem. - 2013. - Vol. 20, N36. - P. 4633-4639.
  35. Jain Z.J., Kankate R.S., Chaudhari B.N., Kakad R.D. Action of benzimidazolo-piperazinyl derivatives on dopamine receptors // Med. Chem. Research. -2013. - V. 22, N2. - P. 520-530. https://doi.org/10.1007/s00044-012-0055-5
  36. Patil A., Ganguly S., Surana S. A systematic review of benzimidazole derivatives as an antiulcer agent // Rasayan J. Chem. - 2008. - V. 1, N3. - P. 447-460.
  37. Галенко-Ярошевский П.А., Галенко-Ярошевский А.П., Анисимова В.А., чемоданова П.С. Производные бензимидазола: местноанестезирующие свойства, механизмы действия, перспективы использования в офтальмологии. - Краснодар: Просвещение_ЮГ. - 2015. -781 с.

Copyright (c) 2019 Chernikov M.V., Oganova M.A., Gerasimenko A.S., Artemyev E.A.

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