Reviews on Clinical Pharmacology and Drug TherapyReviews on Clinical Pharmacology and Drug Therapy1683-41002542-1875Eco-Vector10828810.17816/RCF20175-82Research ArticleAssessment of ethylthiobenzimidazole and fabomotizole activity in a model of hypercapnic hypoxia with cutting off the brain hemispheres workMaryshevaVera V.<p>Dr. Sci. (Pharmacology), Lecturer</p>vvmarysheva@yandex.ruMikheevVladimir V.<p>Dr. Sci. (Pharmacology), Lecturer</p>vvmiheev@mail.ruShabanovPetr D.<p>Dr. Med. Sci. (Pharmacology), Professor and Head of the Department</p>pdshabanov@mail.ruhttps://orcid.org/0000-0003-1464-1127S.M. Kirov Military Medical Academy2705202220175822705202227052022Copyright © 2022, Marysheva V.V., Mikheev V.V., Shabanov P.D.2022<p><strong>BACKGROUND</strong>: Resistance to hypoxia depends on the type of animal, its condition (fatigue, pre-exposure, pregnancy in females) and the conditions of the experiments.</p>
<p><strong>AIM</strong>: study the effect of ethylthiobenzimidazole (Metaprot, Bemityl) and fabomotizole (Afobazole), which were antihypoxants with an isothiourea group, on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one of the cerebral hemispheres.</p>
<p><strong>MATERIALS AND METHODS</strong>: Acute hypoxia with hypercapnia was simulated by the cupping method by placing male mice in a closed hermetic volume (200 cm<sup>3</sup>) until the death of the animal. Previously, in some mice, one of the cerebral hemispheres was temporarily switched off according to the Leao method.</p>
<p><strong>RESULTS</strong>: It has been shown that ethylthiobenzimidazole and fabomotizole, administered intraperitoneally in equimolar doses (25 and 32.8 mg/kg, respectively) 30 min before a hypoxic episode, increase the life time of experimental animals when either of the hemispheres (right or left) is turned off approximately equally.</p>
<p><strong>CONCLUSIONS</strong>: Data are considered in terms of the possibility of using both drugs in the prevention and treatment of ischemic strokes.</p>isothiourea antihypoxantsethylthiobenzimidazole (Metaprot)fabomotizole (Afobazole)hypoxia with hypercapniacerebral hemisphere shutdownischemic strokeантигипоксанты с изотиомочевинной группировкойэтилтиобензимидазол (Метапрот)фабомотизол (Афобазол)гипоксия с гиперкапниейвыключение полушария головного мозгаишемический инсульт[Allikmets LKh, Otter MYa, Eepik TE. Sutochnye i sezonnye kolebaniya rezistentnosti intaktnykh belykh myshei i krys v trekh modelyakh gipoksii. Proccedings of the All-Union Conference dedicated to the 50th anniversary of the Institute of Physiology named after I.S. Beritashvili. Tbilisi: Metsniereba, 1986. P. 18–19.][Balosanyan MG, Kanayan AS, Topchan AV, et al. Neuroprotective activity of afobazole in ischemized brain. Experimental and Clinical Pharmacology. 2021;84(2):23–27. DOI: 10.30906/0869-2092-2021-84-2-23-27][Buresh Ya, Bureshova O, Kh’yuston DP. Metodiki i eksperimenty po izucheniyu mozga i povedeniya. Moscow: Vysshaya shkola; 1991. 400 p.][Kapitsa IG, Ivanova EA, Val’dman EA, et al. Activity of afobazole in experimental models of Parkinson’s disease. Experimental and Clinical Pharmacology. 2017;80(6):39–44. DOI: 10.30906/0869-2092-2017-80-6-3-7][Kryzhanovskii SA, Tsorin IB, Stolyarchuk VN, et al. Studying the cardioprotective effects of fabomotizol hydrochloride on a translation model of chronic heart failure. Bulletin of Experimental Biology and Medicine. 2019;168(7):39–44.][Kryzhanovskii SA, Tsorin IB, Stolyarchuk VN, et al. Delayed results of experimental afobazole therapy in rats after acute myocardial infarction. Bulletin of Experimental Biology and Medicine. 2017;163(2):140–143.][Marysheva VV. Razrabotka i izuchenie biologicheskoi aktivnosti novykh antigipoksantov v ryadakh kondensirovannykh indolov [dissertation abstract]. Saint Petersburg; 2006. 51 p.][Marysheva VV. Antigipoksanty aminotiolovogo ryada. Reviews on Clinical Pharmacology and Drug Therapy. 2007;5(1):17–27.][Marysheva VV, Shabanov PD. Enhancement of physical endurance in animals by means of compounds with thiourea group (review of literature). Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(1):17–30. DOI: 10.7816/RCF17117-30][Marysheva VV, Mikheev VV, Shabanov PD. 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. 2021;19(1): 55–63. DOI: 10.17816/RCF19155-63][Metodicheskie rekomendatsii po eksperimental’nomu izucheniyu preparatov, predlagaemykh dlya klinicheskogo izucheniya v kachestve antigipoksicheskikh sredstv. Luk’yanova LD. ed. Moscow: B.i.; 1990. P. 8.][Mikheev VV, Shabanov PD. Farmakologicheskaya asimmetriya mozga. Saint Petersburg: Elbi-SPb; 2007. 384 p.][Mihkeev VV, Marysheva VV, Bogomolov B, 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. DOI: 10.17816/RCF10151–53][Ostrovskaya RU, Ivanov SV, Voronin MV, et al. Antidiabetic activity of afobazole in Wistar rats. Bulletin of Experimental Biology and Medicine. 2018;165(5):592–596.][Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologichekikh veshchestv. Moscow; 2000. P. 153–158.][Shabanov PD. Klinicheskaya farmakologiya metaprota / Metodicheskie rekomendatsii dlya vrachei. Saint Petersburg: VMedA; 2010. 96 p.]