The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.3.287999

Keywords:

triazolobenzodiazepines, neuromuscular agents, rotarod, vertical grid, coordination

Abstract

Anxiety disorders represent one of the most prevalent categories of psychiatric illnesses, affecting individuals regardless of gender, age, or social standing. They result in substantial personal and societal costs. The pursuit of novel pharmacological approaches for treating these disorders is driven by the increasing medical necessity to enhance the effectiveness and safety profiles of anxiolytic medications. Due to the fact that benzodiazepines and their derivatives have anti-anxiety, hypnotic-sedative, antidepressant, anticonvulsant, and muscle relaxant properties, they occupy a leading place in the treatment of anxiety disorders. An essential aspect of investigating the pharmacological activity of new triazolobenziazepine derivatives is assessing their impact on rodent muscle tone and coordination of movements.

The aim of the work is to find out the influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents in the “vertical grid” test and coordination of movements using the rotarod test.

Materials and methods. The objects of the study were 5 new derivatives of 1,2,3-triazolo-1,4-benzodiazepines. Before conducting in vivo experiments, these derivatives were mixed with lactose at a ratio of 1:1000. The “vertical grid” test and rotarod test (rotating rod test) were used to reproduce the model of motor behavior of rodents.

Results. The presence of a tendency to the manifestation of a myorelaxant effect in the “vertical grid” test was established. The indicator of the total duration of detention at the facilities was similar and did not differ significantly in the control and experimental groups at doses of 0.50 mg/kg and 0.75 mg/kg. Derivatives MA-252, MA-253 and MA-254 at a dose of 1 mg/kg reduced the total duration of retention on the vertical grid, which indicates their mild muscle relaxant effect. In the rotating rod test, MA-253 derivative at a dose of 1 mg/kg increased the retention time on the rotarod, which demonstrates greater physical endurance of the animals of these experimental groups.

Conclusions. The study’s findings indicated that the 1,2,3-triazolo-1,4-benzodiazepine derivatives did not exhibit an adverse impact on movement coordination. Some of these derivatives demonstrated a mild muscle relaxant effect. These results support the need for further research into their influence on spontaneous motor activity. Additionally, there’s a necessity to determine the dosage regimen, establish an effective dose, and adapt it for human use.

Author Biographies

I. V. Botsula, National University of Pharmacy, Kharkiv, Ukraine

PhD Student of the Department of Clinical Pharmacology and Clinical Pharmacy

I. V. Kireyev, National University of Pharmacy, Kharkiv, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Clinical Pharmacology and Clinical Pharmacy

O. M. Koshovyi, National University of Pharmacy, Kharkiv, Ukraine

PhD, DSc, Professor of the Department of Pharmacognosy and Nutriciology

V. A. Chebanov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, DSc, Professor, First Deputy General Director of Scientific Research Department of Chemistry of Functional Materials

References

Bandelow, B., & Michaelis, S. (2015). Epidemiology of anxiety disorders in the 21st century. Dialogues in clinical neuroscience, 17(3), 327-335. https://doi.org/10.31887/DCNS.2015.17.3/bbandelow

American Psychiatric Association. (2022). Anxiety Disorders. In: Diagnostic and Statistical Manual of Mental Disorders. Text Revision. (5th ed., pp. 215-231). American Psychiatric Association.

World Health Organization. (2022, June 16). World mental health report: transforming mental health for all. World Health Organization. License: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/handle/10665/356119

International Organization for Migration. (2023). Ukraine situation. Retrieved March 1, 2023, from https://reporting.unhcr.org/operational/situations/ukraine-situation

International Organization for Migration. (2023). Ukraine: IOM response 2022-2023. Retrieved June 16, 2023, from https://www.iom.int/ukraine-iom-response-2022-2023

Griebel, G., & Holmes, A. (2013). 50 years of hurdles and hope in anxiolytic drug discovery. Nature reviews. Drug discovery, 12(9), 667-687. https://doi.org/10.1038/nrd4075

Koshovyi, O., Raal, A., Kireyev, I., Tryshchuk, N., Ilina, T., Romanenko, Y., Kovalenko, S. M., Bunyatyan, N. (2021). Phytochemical and Psychotropic Research of Motherwort (Leonurus cardiaca L.) Modified Dry Extracts. Plants, 10, 230. https://doi.org/10.3390/plants10020230

Samelyuk, Y. G., & Kaplaushenko, A. G. (2014). Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, Containing methoxyphenyl substituents at c5atoms, Their antipyretic activity, Propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research, 6(5), 1117-1121.

Sameliuk, Y., Kaplaushenko, A., Diakova, F., Ostretsova, L., Nedorezaniuk, N., & Gutyj, B. (2022). Prospects For the Search For New Biologically Active Compounds Among the Derivatives of the Heterocyclic System of 1,2,4-Triazole. Hacettepe University Journal of the Faculty of Pharmacy, 42(3), 175-186. https://doi.org/10.52794/hujpharm.1019625

Shepeta, Yu. L., Lozynskyi, A. V., Nektiehaiev, I. O., & Lesyk, R. B. (2019). Doslidzhennia antyeksudatyvnoi aktyvnosti S-alkilovanykh pokhidnykh 1,3,4-oksadiazol-2-tiolu [The study of antiexudative action of S-alkylated 1,3,4-oxadiazole-3-thionе derivatives]. Current issues in pharmacy and medicine: science and practice, 12(3), 266-269. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2019.3.184184

Safonov, A. A., & Nevmyvaka, A. V. (2020). Actoprotective activity research of 2-((5-(2-bromophenyl)-4-substituted-4H-1,2,4-triazole-3-yl)thio)acetates. Current issues in pharmacy and medicine: science and practice, 13(2), 260-264. https://doi.org/10.14739/2409-2932.2020.2.207196

Guina, J., & Merrill, B. (2018). Benzodiazepines I: Upping the Care on Downers: The Evidence of Risks, Benefits and Alternatives. Journal of clinical medicine, 7(2), 17. https://doi.org/10.3390/jcm7020017

Sayana, S. B., Sampathirao, Y., Munge, B., Moorthy, S., & Burli, K. (2018). Comparative study of centrally acting skeletal muscle relaxants nitrazepam and thiocolchicoside in Albino mice. International Journal of Basic & Clinical Pharmacology, 7(6), 1182. https://doi.org/10.18203/2319-2003.ijbcp20182103

Mazur, M. O., Zhelavskyi, O. S., Zviagin, E. M., Shishkina, S. V., Musatov, V. I., Kolosov, M. A., Shvets, E. H., Andryushchenko, A. Y., & Chebanov, V. A. (2021). Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide-alkyne cycloaddition. Beilstein journal of organic chemistry, 17, 678-687. https://doi.org/10.3762/bjoc.17.57

Directive 2010/63. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. https://eur-lex.europa.eu/eli/dir/2010/63/2019-06-26

National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. (2011). Guide for the Care and Use of Laboratory Animals (8th ed.). National Academies Press. https://www.ncbi.nlm.nih.gov/books/NBK54050/

Lubrich, C., Giesler, P., & Kipp, M. (2022). Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm. International journal of molecular sciences, 23(19), 11342. https://doi.org/10.3390/ijms231911342

Starchenko, G., Hrytsyk, A., Raal, A., & Koshovyi, О. (2020). Phytochemical Profile and Pharmacological Activities of Water and Hydroethanolic Dry Extracts of Calluna vulgaris (L.) Hull. Herb. Plants (Basel, Switzerland), 9(6), 751. https://doi.org/10.3390/plants9060751

Deacon R. M. (2013). Measuring the strength of mice. Journal of visualized experiments : JoVE, (76), 2610. https://doi.org/10.3791/2610

Koshovyi, O., Romanenko, Ye., & Komissarenko, A. (2016). The study of the phenolic composition of the dry extract of motherwort herb and its psychotropic activity. American Journal of Science and Technologies, 1(21), 1055-1059.

Castagné, V., Hernier, A. M., & Porsolt, R. D. (2014). CNS Safety Pharmacology. In Reference Module in Biomedical Sciences. Elsevier. https://doi.org/10.1016/b978-0-12-801238-3.04931-x

Rustay, N. R., Wahlsten, D., & Crabbe, J. C. (2003). Influence of task parameters on rotarod performance and sensitivity to ethanol in mice. Behavioural brain research, 141(2), 237–249. https://doi.org/10.1016/s0166-4328(02)00376-5

Compton, D. R., & Hudzik, T. J. (2015). Neurochemistry of Abuse Liability Assessment and Primary Behavioral Correlates. In Nonclinical Assessment of Abuse Potential for New Pharmaceuticals (pp. 9–48). Elsevier Inc. https://doi.org/10.1016/B978-0-12-420172-9.00002-3

Romanenko, Ye. A., Koshovyi, O. M., Komissarenko, A. M, Golembiovska, O. I., & Gladysh, Yu. I. (2018). The study of the chemical composition of the components of the motherwort herb. News of Pharmacy, (3), 34-38. https://doi.org/10.24959/nphj.18.2222

Romanenko, Y., Koshovyi, O., Ilyina, T., Borodina, N., & Melnyk, N. (2019). Standardization parameters of modified extracts from leonurus cardiaca herb. ScienceRise: Pharmaceutical Science, 17(1), 17-23. https://doi.org/10.15587/2519-4852.2019.157996

Published

2023-11-03

How to Cite

1.
Botsula IV, Kireyev IV, Koshovyi OM, Chebanov VA. The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents. Current issues in pharmacy and medicine: science and practice [Internet]. 2023Nov.3 [cited 2024Oct.12];16(3):217-22. Available from: http://pharmed.zsmu.edu.ua/article/view/287999