ESTABLISHING THE AVERAGE EFFECTIVE DOSE OF 2-HYDROXY-N-NAPHTHALENE-1-IL-2-(2-OXO-1,2-DIHYDRO-INDOL-3-YLIDENE)-ACETAMIDE AT THE «PUNISHABLE BEHAVIOR» MODEL

  • R.V. Lutsenko Poltava state medical university
  • A.G. Sydorenko Poltava state medical university
  • N.O. Vlasenko Poltava state medical university
  • O.A. Lutsenko Poltava state medical university
Keywords: 2-oxoindolins, average effective dose, anxiolytic action.

Abstract

Derivatives of 2-oxoindoline demonstrate significant biological and pharmacological activity, including diuretic, anti-inflammatory, antitumor, antiviral, antibacterial, analgesic, sedative, anticonvulsant and other effects. The aim of this research is to establish the average effective dose of 2-hydroxy-n-naphthalene-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide (compound 18) as a potential anxiolytic, as well as its therapeutic index. Materials and methods of research. The experiments were performed on 36 albino adult male Wistar rats. The average effective dose (ED50) of compound 18 for anxiolytic activity was investigated in the «punishable behavior» test. Rats were divided into 6 groups of 6 animals each. The dose range for the intraperitoneal route of administration was (1, 3, 6; 12, 24, 48 mg/kg). Results and discussion. The «punishable behavior» model, Vogel variant, determined the average effective dose (ED50) and dose-response relationship for 2-hydroxy-n-naphthalene-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide (compound 18) with a single intraperitoneal injection. Analysis of the results shows that the maximum dose that did not cause the effect was 1.0 mg/kg, the minimum effective dose ED16 was 4.5 mg/kg, and the maximum effective dose ED100 was 48 mg/kg. Conclusion. Experimentally determined ED50 of compound 18 in rats when administered intraperitoneally in the «punishable behavior» test, variant Vogel, was 11.9±2.85 mg/kg. The ED50 confidence margins were (4.92÷18.9) mg/kg. According to the therapeutic index, substance 18 exceeds diazepam by 14.8 times.

Downloads

Download data is not yet available.

References

Berezniakova M. Ye., Nikytenko A. O. Vyznachennia efektyvnoi dozy i hostroi toksychnosti khinolinetanu. Za-porozhskyi medytsynskyi zhurnal. 2010. T. 12, №1. S. 49–50.

Veselovskyi A. V., Yvanov A. S., Medvedev A. E. Kom-piuternoe modelyrovanye monoamynoksydaz. Byome-dytsynskaia khymyia. 2015. T. 61, № 2. S. 265–271.

Doklinichne vyvchennia nootropnoi aktyvnosti ta suputnikh psykhotropnykh vlastyvostei pokhidnykh 2– oksoindolinu / O. V. Shatilov, S. Yu. Shtryhol, S. V. Kolisnyk, V. V. Bolotov. Aktualni problemy suchasnoi medytsyny: Vis-nyk Ukrainskoi medychnoi stomatolohichnoi akademii. 2009. T. 9, vyp. 2 (26). S. 139–142.

Doklinichni doslidzhennia likarskykh zasobiv: metodychni rekomendatsii / [Litvinova N.V., Filonenko - Patrusheva M. A., Frantstsuzova S. B. ta in.]: pid red. O.V. Stefano-va. – K.: Avytsena. – 2001. – 528 c.

Zviazok «struktura–diia–aktyvnist» u riadu pokhidnykh 2–oksoindolin–3–hlioksylovoi kysloty / I. I. Shevtsov, V. I. Berezniakov, E. L. Torianik, S. V. Kolisnyk. Medychna khi-miia. 2006. T. 8. № 1. S. 67 – 71.

Kovalova S.V. Syntez, vlastyvosti ta biolohichna akty-vnist efiriv ta amidiv 2–oksoindolinkarbonovykh kys-lot: dys. … kand. farmats. nauk: 15.00.02 / NFaU. Kh., 1999. 146 s.

Lutsenko R. V. Vstanovlennia toksychnosti 2–hidroksy–N–naftalen–1–il–2–(2–oksy–1,2–dyhidroindol–3–iliden)–atsetamidu Visnyk problem biolohii i medytsyny. 2017. Vyp. 4, T. 1 (139). S. 190–193.

Nootropni, antyhipoksychni ta tserebroprotektorni vlas-tyvosti pokhidnykh (2–oksoindoliniliden–3)–otstovoi kys-loty / O. V. Shatilov, S. Yu. Shtryhol, S. V. Kolisnyk, V. V. Bolotov. Bukovynskyi medychnyi visnyk. 2012. T. 16, № 3(63). S. 118–123.

Sydorenko A. H. Poshuk antydepresantiv sered pokhidnykh 2-oksoindolin-3-hlioksynovoi kysloty: dys. … kand. med. Nauk: 14.03.05/ NFaU. Kh., 2016. 185 s.

Sydorenko A. H., Lutsenko R. V. Antydepresyvna ak-tyv-nist pokhidnykh 2–oksoindolin–3–hlioksylovoi kysloty pry modeliuvanni klofelinovoi depresii. Ak-tualni problemy suchasnoi medytsyny: Visnyk Ukrainskoi medy-chnoi stomatolohichnoi akademii. 2012. T. 12, vyp. 4 (40). S. 161–164.

Csende F. Investigation of the intramolecular cycliza-tion of the thiophene substituted cyclohexane skele-ton gamma–oxocarboxylic acid and synthesis of some N–heteroaryl isoindole derivatives. Acta Pharm Hung. 2011. Vol. 81 (2). P. 59–62.

Saravanan G., Alagarsamy V. G., Prakash C. R. Syn-thesis, analgesic, antiinflammatory and ulcerogenic properties of some novel N'–((1–(substituted ami-no)methyl)–2–oxoindolin–3–ylidene)–4–(2–(methyl/phenyl)–4–oxoquinazolin–3 (4H)–yl) benzo-hydrazide deri–vatives. Drug Discov Ther. 2012. Vol. 6, № 2. Р. 78–87.

Synthesis and anticancer potential of certain novel 2–oxo–N'–(2–oxoindolin–3–ylidene)–2H–chromene–3–carbohydrazides / H.A. Abdel–Aziz et al. Eur J Med Chem. 2013. Vol. 70. P. 358–363.

Williams R. B., Hu J. F., Olson K. M. Аntibiotic indole sesquiterpene alkaloid from Greenwayoden–dron suaveolens with a new natural product framework. J. Nat Prod. 2010. Vol. 28, № 73(5). Р. 1008–1011.

Published
2022-04-15
How to Cite
Lutsenko, R., Sydorenko, A., Vlasenko, N., & Lutsenko, O. (2022). ESTABLISHING THE AVERAGE EFFECTIVE DOSE OF 2-HYDROXY-N-NAPHTHALENE-1-IL-2-(2-OXO-1,2-DIHYDRO-INDOL-3-YLIDENE)-ACETAMIDE AT THE «PUNISHABLE BEHAVIOR» MODEL. The Medical and Ecological Problems, 26(1-2), 19-21. https://doi.org/10.31718/mep.2022.26.1-2.05