THE COMPARATIVE STUDYING OF ANTI-HYPOXEMIC ACTIVITY OF COMPLEX OF ZINC ACETATE WITH N-PROPARGYLIMIDAZOLE AND 3-HYDROXYPYRIDINE

The pharmacotherapy of hypoxia is an important task of modern experimental and clinical pharmacology. The medications with anti-hypoxic effect implemented into clinical practice unfortunately do not meet requirements of physicians due to poor efficiency, narrow range of active dosages and undesirable side effects. The complexes of zinc with N-alkenylimidazole demonstrated anti-hypoxic activity at various models of acute hypoxia within large range of dosage. Therefore, further studying of zinc-contained compounds as possible correctors of hypoxia is of particular interest. The experiments with white nonlinear male mice were used for comparative investigation of ant-hypoxic effect of complex compounds of zinc acetate with N-propargylimidazole and 3-hydroxipyridine, including complexes immobilized on sulfated arabinogalaсtan and also well-known anti-hypoxants and/or anti-oxidants: etomerzol, mexidol, nooglutil and hypoxen. It is demonstrated that anti-hypoxic effect of complex of zinc acetate with N-propargylimidazolein conditions of acute hypobaric hypoxia, acute hypoxia with hypercapnia acute hematic hypoxia by width of active dosages (1-100 mg/kg, intraperitoneally) and degree of expression (19-317% in comparison with control groups of animals) excels the similar effect in well-known anti-hypoxants and/or anti-oxidants: etomerzol (25-100 mg/kg, intraperitoneally), mexidol (100 mk per kg, intraperitoneally), nooglutil (25-100 mg/kg, intraperitoneally) and hypoxen (50-150 mg/kg, intraperitoneally). The protective effect of complex of zinc acetate with 3-hydroxipyridine by width of active dosages (25-100 mg/kg, intraperitoneally) and degree of expression (27-167% in comparison with control groups of animals) in conditions of exogenous hypoxia (acute hypobaric hypoxia and acute hypoxia with hypercapnia) excels similar effect of etomerzol and mexidol ans is comparable with effect of nooglutil and hypoxen. The complexes immobilized on sulfated arabinogalactan were ineffective.

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Potentiation of the hypoxic preconditioning effect by antihypoxants

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf17137-44 ◽

2019 ◽

Vol 17 (1) ◽

pp. 37-44

Author(s):

Vasiliy E. Novikov ◽

Olga S. Levchenkova ◽

Elena I. Klimkina ◽

Konstantin N. Kulagin

Keyword(s):

Hypobaric Hypoxia ◽

Carotid Arteries ◽

Acute Hypoxia ◽

Hypoxia Inducible Factor ◽

Experimental Models ◽

Hypoxic Preconditioning ◽

Acute Hypobaric Hypoxia ◽

Hypoxia With Hypercapnia ◽

The Common ◽

Common Carotid Arteries

The development of effective methods to increase the organism resistance to hypoxia is an important task of current medicine. One of such methods is preconditioning, as a result of which, a potent mobilization of the adaptive organism abilities occurs under a preconditioning factor action. Aim. To study the possibility of potentiating of the hypoxic preconditioning effect with help of antihypoxants. Methods. Evaluation of the effectiveness of combined preconditioning (antihypoxants + moderate hypobaric hypoxia) was performed on experimental models of acute hypoxia with hypercapnia, acute hypobaric hypoxia in mice, and bilateral occlusion of the common carotid arteries in rats. Investigated antihypoxants are amtizol, hypoxen, cobazole, metaprot, mexidol, mildronate, substances under the codes VM-606, pQ-4 and pQ-1104. Results. PreC with use of amtizol at dose 25 mg/kg, cobazole at dose 30 mg/kg, VM-606, pQ-4 and pQ-1104 at doses 50 mg/kg in combination with moderate hypoxia increased the lifespan of mice in acute hypoxia with hypercapniamodel and acute hypobaric hypoxia from 57 to 170%. Combined preconditioning with amtizol, cobazole and pQ-4 significantly increased the survival rate of rats in cerebral ischemia, amtizol and pQ-4 reduced neurological deficiency in the post ischemic period as well. Conclusion. Antitipoxants as amtizol, cobazole, VM-606, pQ-4, pQ-1104 potentiate the hypoxic preconditioning effect on acute hypoxia with hypercapnia, acute hypobaric hypoxia and occlusion of the common carotid arteries models, the most significant effect was noted for amtizol and pQ-4. Signal role in the adaptation induction to hypoxia and ischemia by combined preconditioning with use of antihypoxants hypoxia-inducible factor HIF-1α can play.

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Study of antihypoxic activities of metal complex selenium containing substances after their parenteral and enteralintroductions

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf10328-34 ◽

2012 ◽

Vol 10 (3) ◽

pp. 28-34

Author(s):

Denis Vladimirovich Sosin ◽

Andrey Viktorovich Yevseyev ◽

Edgar Andreyevich Parfenov ◽

Vitaliy Andreyevich Pravdivtsev ◽

Marina Anatolyevna Yevseyeva ◽

...

Keyword(s):

Metal Complex ◽

Hypobaric Hypoxia ◽

Protective Action ◽

Complex Compounds ◽

Acute Hypobaric Hypoxia ◽

Hypercapnic Hypoxia ◽

First Time

In experiments on mice undergone to an acute hypercapnic hypoxia and an acute hypobaric hypoxia a screening of antihypoxants among new selenium containing metal complex substances was performed after their intra-abdominal and oral introductions. It was found that substances πQ1983 and πQ2170 on both models of hypoxia make the defensive effects surpassing actions well-known antihypoxants such as amthizole and bemythil. It was shown that antihypoxiс affects of studied substances depend on their caused hypothermia. For the first time the protective action of selenium containing metal complex compounds was demonstrated after their introduction per os.

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II-Valent metals complex compounds and prospects of the acute hypoxia protection

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf17153-56 ◽

2019 ◽

Vol 17 (1) ◽

pp. 53-56

Author(s):

Andrey V. Evseev ◽

Albert E. Belenky ◽

Dmitrij V. Surmenev ◽

Marina A. Evseeva ◽

Denis V. Sosin

Keyword(s):

Protective Effect ◽

Rectal Temperature ◽

Active Substance ◽

Acute Hypoxia ◽

Complex Compounds ◽

Antihypoxic Activity ◽

Reference Substance ◽

Divalent Metals ◽

Hypoxia With Hypercapnia ◽

Antihypoxic Effect

Aim. To find antihypoxic properties in complex compounds of some divalent metals on the model of acute hypoxia with hypercapnia. Methods. In the experiments on mice in acute hypoxia with hypercapnia (AH+Hc), the protective effect of 6 new complex compounds was studied in comparison with the effectiveness of reference antihypoxants. Substances were injected intraperitoneally 60 min before acute hypoxia with hypercapnia in doses of 25 and 50 mg/kg. Antihypoxic effect was compared with their ability to change the rectal temperature. Results. The most active substance πQ-2116 with Nickel as a complexing metal was established. Mice resistance to acute hypoxia with hypercapnia at a dose of 25 mg/kg was increased to 89.5%, at a dose of 50 mg/kg – to 165.8%. The effect was accompanied by serious hypothermia, reaching 28.5 °C. Antihypoxic activity of the substance πQ-2116 is comparable with reference substance πQ-1983 and greater than the effect of aminothiol antihypoxants – Amtizole and Sunazole.

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Influence of the new tiazoloindole derivative on the organism resistance to hypoxia in the early and late periods of preconditioning

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf12454-57 ◽

2014 ◽

Vol 12 (4) ◽

pp. 54-57

Author(s):

Olga Sergeevna Levchenkova ◽

Vasiliy Egorovich Novikov ◽

Vera Vasil'yevna Marysheva

Keyword(s):

Early Phase ◽

Hypobaric Hypoxia ◽

Acute Hypoxia ◽

Late Phase ◽

Animal Life ◽

Resistance To Hypoxia ◽

Hypoxia With Hypercapnia

The aim of this investigation was to study an ability of tiazoloindole derivative encoded VM-606 to influence the lifespan of mice in experimental acute hypoxia with hypercapnia and hypobaric hypoxia in early and late phase of preconditioning. It was found that the use of VM- 606 in dose of 50 mg/kg leads to significant increase in the duration of animal life in case of subsequent acute hypoxia in early phase of preconditioning, but doesn’t produce effect in the late phase of preconditioning.

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Comparative analysis of metal-complex and aminothiol antihypoxants efficiencies in the experiment

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf16218-24 ◽

2018 ◽

Vol 16 (2) ◽

pp. 18-24

Author(s):

Andrey V Evseev ◽

Dmitrij V Surmenev ◽

Marina A Evseeva ◽

Denis V Sosin ◽

Yana V Tishkova

Keyword(s):

Clinical Pharmacology ◽

Comparative Analysis ◽

Metal Complex ◽

Rectal Temperature ◽

Acute Hypoxia ◽

Male Rats ◽

Antihypoxic Activity ◽

Control Groups ◽

Hypoxia With Hypercapnia ◽

Antihypoxic Effect

Aim. Comparative analysis of the efficiency of metal-complex (πQ1983, πQ2721) and aminothiol (Amtizole, Sunazole) antihypoxants in experiments on rats exposed to acute hypoxia with hypercapnia. Methods. Experiments performed on 182 male rats of Wistar line weighing 150-170 g. The study of antihypoxic activity of substances was carried out on the model the AH+Hc. The condition of acute hypoxia in rats was formed by placing them in glass airtight containers with a free volume of 1.0 L. Antihypoxic effect was evaluated by the life expectancy of animals in the described conditions. Substances πQ2721, πQ1983, Amtizole and Sunazole was administered once intraperitoneally at doses of 25, 50 and 100 mg/kg. Previously each substance was dissolved in 0.9% NaCl (1.0 ml). Testing the effectiveness of the substances on AH+Hc model was carried out after 1 h after administration of the substances and after 24 h. Animals of control groups were injected with 1.0 ml of 0.9% NaCl. In animals exposed to test AH+Hc in 1 h after administration were performed measurements of the rectal temperature before the experiment and through 1 h after administration, i.e. before AH+Hc. In animals selected for 24-hour observation, rectal temperature was measured before the experiment, and then after 1, 3, 6, 12, 18 and 24 h of observation, after which they were exposed to AH+Hc. Results. The antihypoxic effect of a selenium-containing substance πQ2721 based on Zn2+ was confirmed in experiments on rats. In a number of substances for comparison the πQ2721 proved himself not only as equally effective. It is found that after 1 h after administration at a dose of 50 mg/kg πQ2721 superior to all studied compounds, including antihypoxant with succinate Sunazole. An important advantage of the new promising antihypoxic agent was the preservation of its action for 24 hours after injection. (For citation: Evseev AV, Surmenev DV, Evseeva MA, et al. Comparative analysis of metal-complex and aminothiol antihypoxants efficiencies in the experiment. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):18-24. doi: 10.17816/RCF16218-24).

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Influence of the new tiazoloindole derivative on organism resistance to hypoxia in the early and late periodsof preconditioning

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf13152-55 ◽

2015 ◽

Vol 13 (1) ◽

pp. 52-55

Author(s):

Ol'ga Sergeevna Levchenkova ◽

Vasiliy Egorovich Novikov ◽

Vera Vasil'yevna Marysheva

Keyword(s):

Early Phase ◽

Hypobaric Hypoxia ◽

Acute Hypoxia ◽

Late Phase ◽

Animal Life ◽

Resistance To Hypoxia ◽

Hypoxia With Hypercapnia

The aim of this investigation was to study an ability of tiazoloindole derivative encoded VM-606 to influence the lifespan of mice in experimental acute hypoxia with hypercapnia and hypobaric hypoxia in early and late phase of preconditioning. It was found that the use of VM-606 in dose of 50 mg/kg leads to significant increase in the duration of animal life in case of subsequent acute hypoxia in early phase of preconditioning, but doesn’t produce effect in the late phase of preconditioning.

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