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

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Abstract

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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About the authors

Vera V. Marysheva

S.M. Kirov Military Medical Academy

Author for correspondence.
Email: vvmarysheva@yandex.ru

Dr. Biol. Sci. (Pharmacology), Assistant Professor

Russian Federation, 6 Acad. Lebedev str., Saint Petersburg, 194044

Vladimir V. Mikheev

S.M. Kirov Military Medical Academy

Email: vvmiheev@mail.ru

Dr. Sci. (Biol.)

Russian Federation, 6 Acad. Lebedev str., Saint Petersburg, 194044

Petr D. Shabanov

S.M. Kirov Military Medical Academy

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477

Dr. Med. Sci. (Pharmacology), Professor

Russian Federation, 6 Acad. Lebedev str., Saint Petersburg, 194044

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