Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Behavior in Rats

Ivanova, E. A.; Matyushkin, A. I.; Vasilchuk, A. G.; Воронина, Т. А.

doi:10.3103/s009639252103007x

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…This calls for the search for and development of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system, in order to create new drugs with an appropriate mechanism of action. Numerous studies have demonstrated that the medications atmizole, hesperidin, hypoxene, petaprot, acizole and mexidol, combining antihypoxant and antioxidant properties, have anti-inflammatory effects and are also able to greatly increase the therapeutic efficacy of NSAIDs (Bobr et al 2010;Novikov et al 2010;Turgeneva et al 2011;Babaniyazova et al 2013;Novikov and Ilyukhin 2013;Pozhilova 2014;Maskurova et al 2018;Ivanova et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative

Galenko-Yaroshevsky,

Shelemekh,

Popkov

et al. 2024

RRP

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Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative. Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically. Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity. Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.

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Section: Introductionmentioning

confidence: 99%

Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative

Galenko-Yaroshevsky,

Shelemekh,

Popkov

et al. 2024

RRP

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Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Blood Pressure and Hematological Indices in Rats

Vasilchuk

Ivanova

Matyushkin

et al. 2022

Moscow Univ. Biol.Sci. Bull.

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Effect of multiple-dose regimens of cyclooxygenase inhibitors and their combinations with mexidol on behavior in mature rats

Ivanova

Vasilchuk

Matyushkin

et al. 2023

Fk&Fd

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Effects of multiple-dose regimens (oral, daily, once a day for 15 days) of cyclooxygenase (COX) inhibitors etoricoxib (1 and 10 mg/kg), diclofenac sodium (1 and 5 mg/kg) and their combinations with 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol 25 mg/kg) on rat behavior were studied in the open field test, rotarod test and elevated plus maze test. Exploratory (in open field test) and locomotor (in rotarod test) behavior of rats was significantly weakened only by the non-selective COX inhibitor diclofenac sodium at 5 mg/kg, which is due to the peripheral side effect of the drug. The selective COX-2 inhibitor etoricoxib increased the time in the central area of the elevated plus maze at 1 and 10 mg/kg and reduced the latent period of locomotion in the open field test at 10 mg/kg. A combination of diclofenac sodium (1 mg/kg) with mexidol neither reduced exploratory behavior nor caused motor deficit in contrast to diclofenac sodium at 5 mg/kg. However, a combination of etoricoxib (1 mg/kg) with mexidol inhibited locomotor activity in the rotarod test. Nevertheless, it produced no significant effects on the exploratory behavior or anxiety of animals in the open field test and elevated plus maze test.

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Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Behavior in Rats

Cited by 3 publications

References 18 publications

Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative

Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative

Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Blood Pressure and Hematological Indices in Rats

Effect of multiple-dose regimens of cyclooxygenase inhibitors and their combinations with mexidol on behavior in mature rats

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