Reviews on Clinical Pharmacology and Drug TherapyReviews on Clinical Pharmacology and Drug Therapy1683-41002542-1875Eco-Vector7061910.17816/RCF19155-63Research ArticleEvaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheresMaryshevaVera V.<p>Dr. Biol. Sci. (Pharmacology), Assistant Professor</p>vvmarysheva@yandex.ruMikheevVladimir V.<p>Dr. Sci. (Biol.)</p>vvmiheev@mail.ruShabanovPetr D.<p>Dr. Med. Sci. (Pharmacology), Professor</p>pdshabanov@mail.ruhttps://orcid.org/0000-0003-1464-1127S.M. Kirov Military Medical Academy1503202119155631405202114052021Copyright © 2021, Marysheva V.V., Mikheev V.V., Shabanov P.D.2021<p><em>PURPOSE:</em> To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-<em>b</em>]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.</p>
<p><em>METHODS: </em>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-<em>b</em>]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.</p>
<p><em>RESULTS:</em> 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.</p>
<p><em>CONCLUSION: </em>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.</p>antihypoxants with an isothiourea groupamtizol2-aminobenzthiazole2-amino-4-acetylthiazolo[5,4-b]indolehypoxia with hypercapniashutdown of one of the hemispheres and both hemispheresантигипоксанты с изотиомочевинной группировкойамтизол2-аминобензотиазол2-амино-4-ацетилтиазоло[5,4-b]индолгипоксия с гиперкапниейотключение работы одного из полушарий и обеих гемисфер[Allikmets LH, Otter MYa, Eepik TE. Sutochnye I sezonnye kolebaniya pezistentnosti inbrendnykh belykh myshei I krys v trekh modelyakh gipoksii. Tezisy Vsecoyuznoi konferentsii posvyaschennoi 50-letiyu Instituta fiziologii imeni IS Beritashvili. Tbilisi: Metsniereba; 1986. P. 18–19 (In Russ.)][Byresh Ya, Bureshova O, Huston DP. Metodiki I ersperimenty po izucheniyu mozga I povedeniya. Moscow: Vysshaya shkola; 1991. 400 p. (In Russ.)][Zarubina IV., Shabanov PD. Antigipoksanty pri cherepno-mozgovoi travme. Saint Petersburg: Elbi-SPb; 2006: 384 p. (In Russ.)][Kochinova OF, Zubkova IV, Chernykh VP. Sintez, reaktsionnaya sposobnost’ I biologicheskaya aktivnost’ proizvodnykh 2-aminobenztiazola. Khar’kov: Izdatel’stvo NFAU; 2000. 165 p. (In Russ.)][Marysheva VV, Shabanov PD. Antihypoxant activity in a series of 2-aminothiazole homologs. Experimental and Clinical Pharmacology. 2005;68(1):67–70. (In Russ.)][Marysheva VV. Razrabotka I izuchenie biologicheskoi aktivnosti novykh antigipoksantov v ryadakh kondensirovannykh indolov [dissertation abstract]. Saint Petersburg; 2006. 51 p. (In Russ.)][Marysheva VV. Antigipoksanty aminotiolovogo ryada. Reviews on Clinical Pharmacology and Drug Therapy. 2007;5(1):17–27. (In Russ.)][Metodicheskie rekomendatsii po eksperimental’nomu izucheniyu preparatov, predlagaemykh dlya klinicheskogo izucheniya v kachestve antigipoksicheskikh sredstv. LD. Lukyanova ed. Moscow; 1990. 8 p. (In Russ.)][Mikheev VV, Shabanov PD. Farmakologicheskaya asimmetriya mozga. Saint Petersburg: Elbi-SPb; 2007. 384 p. (In Russ.)][Mikheev VV, Marysheva VV, Bogomolov BN, Zhukova-Williams LV. Effect of aminothiol antihypoxants on interhemispheric asymmetry of the brain. Reviews on Clinical Pharmacology and Drug Therapy. 2012;10(1):51–53 (In Russ.) DOI: 10.17816/RCF10151-53][Novikov VE, Dikmanov VV, Marysheva VV. Effect of a new triazinoindole derivative on the functional state of cns in animals under normoxia and hypoxia conditions. Experimental and Clinical Pharmacology. 2012:75(9):7–10. (In Russ.) DOI: 10.30906/0869-2092-2012-75-9-7-10][Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh sredstv. Fisenko VP, ed. Moscow; 2000. P. 153–158. (In Russ.)][Smirnov AV, Krivoruchko BI. Antigiporsanty v neotlozhnoi meditsine. Anesteziologiya i Reanimatologiya. 1998;2:50–55. (In Russ.)]