The experimental study of the antihypoxic properties of harmine hydrochloride

A derivative of the beta-carboline alkaloid harmine — the drug harmine hydrochloride was studied for the presence of antihypoxic properties in models of hypobaric hypoxia and normobaric hypoxia with hypercapnia. It was found that harmine hydrochloride does not have a signifi cant compensatory effect in the normobaric hypoxia test with hypercapnia. At the same time, harmine hydrochloride in small doses (2.5 and 5 mg/kg) has antihypoxic activity in the hypobaric hypoxia test, which is expressed in a statistically signifi cant increase in the life expectancy of animals treated with the drug, compared with the control, in conditions of hypoxia. According to the antihypoxic effect, harmine hydrochloride at doses of 2.5 and 5 mg/kg was found to be comparable with the reference drug (mexidol, 100 mg/kg).

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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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EFFECT OF AMINOTHIOL ANTIHyPOXANTS ON INTERHEMISPHERIC ASyMMETRy OF THE bRAIN

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf10151-53 ◽

2012 ◽

Vol 10 (1) ◽

pp. 51-53

Author(s):

Vladimir Vladimirovich Mihkeev ◽

Vera Vasilievna Marysheva ◽

Boris Nikolaevich Bogomolov ◽

Lubov Vladislavovna Zhukova-Williams

Keyword(s):

Left Hemisphere ◽

Right Hemisphere ◽

Acute Hypoxia ◽

Life Time ◽

Antihypoxic Activity ◽

Interhemispheric Relations ◽

Hypoxia With Hypercapnia ◽

Antihypoxic Effect ◽

The Right ◽

The Brain

The effect of aminothiol antihipoxants amthizol and its analogue VM-606 on the resistance of the SHR mice males to an acute hypoxia with hypercapnia under conditions of isolated functioning of one of the hemispheres of the brain was studied. Antihypoxic agent amthizol 25 mg/kg increases life time of naïve mice by 46.2%. The drug acted on the sham-operated mice more slightly, increasing of their life only on 28.1% (p<0.01). Administration of amthizol under conditions of functioning of the right hemisphere significantly enhanced (+64.8%) the life time of mice. No antihypoxic effect was registered after administration of amthizol to mice with active left hemisphere: the result was the same as in mice without amthizol. Therefore, antihypoxic effect of amthizol was due to its action on the right (but not the left) hemisphere of the brain. VM-606 possessed more antihypoxic activity in comparison with amthizol. After unilateral cortical inactivation, VM-606 increased life time of mice both in active right and active left hemispheres, but in more degree in active right hemisphere. Thus, interhemispheric differences in resistance of mice to hypoxia with hypercapnia were diminished. Therefore, the differences between amthizol and VM-606 are the followings: amthizol inverts interhemispheric relations in hypoxia whereas VM-606 diminishes them.

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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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Antihypoxic activity of the VMA-10-18 derivate under hypobaric hypoxia in mice

Archiv Euromedica ◽

10.35630/2199-885x/2020/10/4.6 ◽

2020 ◽

Vol 10 (4) ◽

pp. 29-30

Author(s):

Anastasia Gerashchenko ◽

Natalia Shabanova ◽

Andrey Voronkov

Keyword(s):

Hypobaric Hypoxia ◽

Life Time ◽

Test Site ◽

Control Group ◽

Antihypoxic Activity ◽

Acute Hypobaric Hypoxia ◽

Reference Drug

The present study was carried out to evaluate the effect of a new derivative VMA-10-18 (10 mg/kg) on the resistance of mice to acute hypobaric hypoxia. It was confirmed that the studied derivative contributes to an increase in the life time on the lethal test site by 2,7 times (p <0,05) compared with the control group of animals and exceeds the strength of the effect of the reference drug Metaprot by 1,2 (p <0,05).

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EXPERIMENTAL STUDY OF THE EFFICACY OF L-LYSINE-A-OXIDASE TRICHODERMA CF. AUREOVIRIDE RIFAI ON MODELS OF XENOGRAFTS OF HUMAN TUMORS IN ATHYMIC MICE AND EVALUATION OF SYNERGISM WITH CISPLATIN OR TOPOISOMERASE INHIBITORS

Problems in oncology ◽

10.37469/0507-3758-2017-63-3-497-505 ◽

2017 ◽

Vol 63 (3) ◽

pp. 497-505

Author(s):

Vadim Pokrovskiy ◽

Yelena Lukasheva ◽

Nikolay Chernov ◽

Yelena Treshchalina

Keyword(s):

Experimental Study ◽

Life Expectancy ◽

Therapeutic Benefit ◽

Human Tumors ◽

Lymphocytic Leukemia ◽

Antitumor Drugs ◽

Athymic Mice ◽

Lewis Lung ◽

Topoisomerase Inhibitors ◽

Inhibition Of Growth

The effectiveness of L-lysine-alpha oxidase Trichoderma cf. Aureoviride Rifai BKMF-4268D (LO) on models of subcutaneous xenografts of human tumors in athymic mice as well as the effectiveness of combination therapy with known antitumor drugs: cisplatin, irinotecan, etoposide on models of P388 lymphocytic leukemia, Lewis lung (LLC) and B16 melanoma was evaluated. The intraperitoneal injection of LO in a discrete regime at doses of 150-75-75-75-75 E/kg demonstrated inhibition of growth of all studied xenografts of human tumors in athymic mice. The combination of irinotecan+LO on the LLC model gave a significant summative therapeutic benefit with an increase in mouse life expectancy up to 35%. Cisplatin and LO realized a significant (p

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Evaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheres

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf19155-63 ◽

2021 ◽

Vol 19 (1) ◽

pp. 55-63

Author(s):

Vera V. Marysheva ◽

Vladimir V. Mikheev ◽

Petr D. Shabanov

Keyword(s):

Acute Hypoxia ◽

Life Time ◽

The Body ◽

Cerebral Hemispheres ◽

Antihypoxic Activity ◽

Hypoxic Episode ◽

Hypoxia With Hypercapnia ◽

Hypercapnic Hypoxia ◽

Outbred Mice ◽

The Brain

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.

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Counterpoint: Hypobaric hypoxia does not induce different responses from normobaric hypoxia

Journal of Applied Physiology ◽

10.1152/japplphysiol.00067.2012a ◽

2012 ◽

Vol 112 (10) ◽

pp. 1784-1786 ◽

Cited By ~ 35

Author(s):

Remi Mounier ◽

Julien V. Brugniaux

Keyword(s):

Hypobaric Hypoxia ◽

Normobaric Hypoxia

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Effect of repeated normobaric hypoxia exposures during sleep on acute mountain sickness, exercise performance, and sleep during exposure to terrestrial altitude

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00633.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. R428-R436 ◽

Cited By ~ 55

Author(s):

Charles S. Fulco ◽

Stephen R. Muza ◽

Beth A. Beidleman ◽

Robby Demes ◽

Janet E. Staab ◽

...

Keyword(s):

Heart Rate ◽

Exercise Performance ◽

Hypobaric Hypoxia ◽

Sham Group ◽

Acute Mountain Sickness ◽

Time Trial ◽

Normobaric Hypoxia ◽

Performance Decrement ◽

Mountain Sickness ◽

End Tidal

There is an expectation that repeated daily exposures to normobaric hypoxia (NH) will induce ventilatory acclimatization and lessen acute mountain sickness (AMS) and the exercise performance decrement during subsequent hypobaric hypoxia (HH) exposure. However, this notion has not been tested objectively. Healthy, unacclimatized sea-level (SL) residents slept for 7.5 h each night for 7 consecutive nights in hypoxia rooms under NH [ n = 14, 24 ± 5 (SD) yr] or “sham” ( n = 9, 25 ± 6 yr) conditions. The ambient percent O2 for the NH group was progressively reduced by 0.3% [150 m equivalent (equiv)] each night from 16.2% (2,200 m equiv) on night 1 to 14.4% (3,100 m equiv) on night 7, while that for the ventilatory- and exercise-matched sham group remained at 20.9%. Beginning at 25 h after sham or NH treatment, all subjects ascended and lived for 5 days at HH (4,300 m). End-tidal Pco2, O2 saturation (SaO2), AMS, and heart rate were measured repeatedly during daytime rest, sleep, or exercise (11.3-km treadmill time trial). From pre- to posttreatment at SL, resting end-tidal Pco2 decreased ( P < 0.01) for the NH (from 39 ± 3 to 35 ± 3 mmHg), but not for the sham (from 39 ± 2 to 38 ± 3 mmHg), group. Throughout HH, only sleep SaO2 was higher (80 ± 1 vs. 76 ± 1%, P < 0.05) and only AMS upon awakening was lower (0.34 ± 0.12 vs. 0.83 ± 0.14, P < 0.02) in the NH than the sham group; no other between-group rest, sleep, or exercise differences were observed at HH. These results indicate that the ventilatory acclimatization induced by NH sleep was primarily expressed during HH sleep. Under HH conditions, the higher sleep SaO2 may have contributed to a lessening of AMS upon awakening but had no impact on AMS or exercise performance for the remainder of each day.

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