Analgesic and anti-inflammatory activity of 5,7-diacyl-3-H(alkіl)-6- aryl-5H-[1,2,4]triazol[3,4-b][1,3,4]tіadiazin derivaties
DOI:
https://doi.org/10.11603/mcch.2410-681X.2015.v17.i2.4866Abstract
The search for new analgesic and anti-inflammatory drugs, exceeding by efficacy and/or safety the existinganalogues is very important and relevant. The nitrogenous heterocycles are promising in this respect, in particular,
the compounds containing an imidazole triazol and tіadiazin moiety. The aim of the current study was to investigate
the antiexudative and antinociceptive activity of new derivatives of 5,7-diacyl-3-H(alkyl)-6-aryl-5H[1,2,4]triazol[3,4-b]
[1,3,4]thiadiazine.
The antinociceptive and antiexudative activity studies were carried out on the white nonlinear mice. The
experimental evaluation of specific activity was carried out on the models “Hot plate”, acetic acid induced writhing
(antinociceptive action) and carrageenan edema (antiexudative action). The substance was used in a single oral rout
administration in a dose of 25 mg/kg. Ketorolac was used as a reference product in the dose of 25 mg/kg (models
“Hot plate”, acetic acid induced writhing). Diclofenac was used as a reference product in the dose of 25 mg/kg on
the model carrageenan edema. The experimental study showed the antinociceptive and antiexudative effects of the
derivatives. The antinociceptive activity of 5,7-diacyl-3-H(alkіl)-6-aryl-5H[1,2,4]triazol[3,4-b][1,3,4]tіadiazin derivaties
related to the modification structure in the para position of benzene ring. The antiexudative activity is associated with
acetyl groups thiadiazine ring. The most promising compound IFT_247 showed a significant antinociceptive effect,
which is comparable to an active comparator ketorolac: “Hot plate” +232.46 % and +112.71 %; acetic acid induced
writhing -66.67 % and -61.02 %, respectively.
References
Каннер Р. Секреты лечения боли / Р. Каннер ;
пер. с англ. – М. : БИНОМ, 2006. – 400 с.
Лапач С. Н. Статистика в науке и бизнесе /
С. Н. Лапач, А. В. Чубенко, П. Н. Бабич. – К. : Морион,
– 640 с.
In vivo модели для изучения анальгетиче-
ской активности / Д. А. Бондаренко, И. А. Дьяченко,
Д. И. Скобцов, А. Н. Мурашев // Биомедицина. –
– № 2. – С. 84–94.
Насонова В. А. Диклофенак натрия (вольтарен):
“золотой стандарт” среди неселективных противовос-
палительных препаратов (обзор литературы) [элек-
тронный ресурс] / В. А. Насонова. – Режим доступа :
http://www.paininfo.ru/articles/consilium_medicum/3523.
html.
Стефанов О. В. Доклінічні дослідження лікарських
засобів : метод. рек. / за ред. О. В. Стефа-
нова. – К. : Авіцена, 2001. – 528 с.
Тринус Ф. П. Нестероидные противовоспа-
лительные средства / Ф. П. Тринус, Н. А. Мохорт,
Б. М. Клебанов. – К. : Здоров’я, 1975. – 240 с.
A double-blind, multicenter trial comparing
duloxetine with placebo in the treatment of fibromyalgia
patients with or without major depressive disorder /
L. M. Arnold, Y. Lu, L. J. Crofford [et al.] // Arthritis
Rheum. – 2008. – 50, № 9. – P. 2974–2984.
Analgesic and anesthetic Drug. Analgesic
Drug.462707 // Drug Data Report. – 2007. – 29, № 10.
– P. 887–888.
Analgesic and spazmolitic action of 2-(2-nitrophenyl)-
H-benzimidazole 5-carboxylic acid: impotent of
-(o-change phenyl) groope / S. Aydin, R. Beis, S. Aydin
[et al.] // Pharmazie. – 2003. – 58, № 6. – P. 405–408.
Analgesic effects of lidocaine, morphine and
diclofenac on movement-induced nociception, as assessed
by the Knee-Bend and CatWalk tests in a rat
model of osteoarthritis / J. Ferreira-Gomes, S. Adães,
M. Mendonça [et al.] // Pharmacology Biochemistry and
Behavior. – 2012. – 101, № 4. – P. 617–624.
Autret E. Evaluation of ibuprofen versus aspirin
and paracetamol on efficacy and comfort in children with
fever / E. Autret // Eur. J. Clin. Pharmacol. – 1997. – 51,
№ 5. – Р. 367–371.
D`Amoue F. E. A method for determining lose of
pain sensation / F. E. D`Amoue, D. L. Smalh // J. Pharmacol.
Exp. Ther. – 1941. – 72. – Р. 74.
DrugBank database, DrugBank Version: 3.0
[Electronic resourse]. – Access mode: http://www.drugbank.
ca/.
Goodman A. The pharmacological basis of Therapeutic
(9th ed.) / A. Goodman, L. Gilman. – New York :
McGraw-Hill, 1996. – Ch. 27. – P. 836–932.
Incidence rates and treatment of neuropathic
pain conditions in the general population / J. P. Dieleman,
J. Kerklaan, F. J. P. M. Huygen [et al.] // Pain. – 2008. –
, № 3. – P. 681–688.
Komlos E. Morfin – prostigmin synergismus /
E. Komlos, J. Porsresr, J. Knole // Az. Acta. Phisiologica.
Acad. Scient. Hungaricae. – 1950. – № 1. – Р. 77–83.
Local infiltration analgesia for total knee arthroplasty:
should ketorolac be added? / K. V. Andersen,
L. Nikolajsen, V. Haraldsted [et al.] // Br J Anaesth. – 2013
(doi: 10.1093/bja/aet030).
Vogel W. H. Drug Discovery and Evaluation:
Pharmacological Assays. Second Edition. [Electronic resourse]
/ W. H. Vogel. – Access mode : http://web.squ.edu.
om/med-Lib/MED_CD/E_CDs/Drug%20Discovery%20
and%20Evaluatuon%202002/start.pdf).
Which Treatment for Postherpetic Neuralgia? /
K. Hempenstall, T. J. Nurmikko, R. W. Johnson [et. al.] //
PloS Medicine (PloS Med). – 2005. – 2, № 7. – P. 238.
Wood R. L.Animal models in analgesic testing /
R. L. Wood // Analgesics: Neurochemical, Behavioral
and Clinical perspectives. Kuhar M., Pasternak J. (Eds)
Raven Press. – 1941. – 42. – Р. 74.
