Place of tiotriazoline in the gallery of modern metabolitotropic medicines

Authors

  • I. F. Bielenichev Zaporizhzhia State Medical University, Ukraine,
  • V. A. Vіzіr Zaporizhzhia State Medical University, Ukraine,
  • V. Yo. Mamchur SI “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro,
  • O. V. Kuriata SI “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro,

DOI:

https://doi.org/10.14739/2310-1210.2019.1.155856

Keywords:

Thiotriazolin, pharmacokinetics, harmlessness, cardioprotonic agents, clinical effictiveness

Abstract

We want to show pharmacological characterization of Tiotriazoline, based on results of tentative analysis and clinical research, also features of its therapeutic action and advantage over another metabolitotropic cardio protectors. As a result of the literary sources analysis, we found out that the team of scientists led by professor I. A. Mazur had developed and created qualitatively new innovative medicine of cation-anionic action, namely Thiotriazolin, which is based on 1,2,4-triazole molecule and was selected among more than 1000 compounds. This drug is the first representative of the class of metabolitotropic cyto- and cardioprotectors and it exhibits anti-ischemic, cardioprotective, antioxidant, energotropic, membrane-protective and immunomodulating properties and is widely used to treat diseases of the cardiovascular system and eye diseases. The mechanism of action of Thiotriazolin is to increase the expression of antioxidant enzymes, reduce the concentration of free radicals, activate a compensatory malate-aspartate shunt of energy production, normalize the work of the Krebs cycle, and initiate Red / Oxi-dependent expression of transcription factors in ischemia. Using the example of pharmacodynamics and clinical efficacy of Thiotriazoline, the modern concept of metabolitotropic cardioprotection was further developed. Thiotriazolin belongs to V class of toxicity (practically non-toxic substances). Thiotriazolin reduces the number and duration of ischemia episodes, cardiac arrhythmias, increases tolerance to physical activity, and also improves the quality and lifetime (assessed using the Minnesota questionnaire and Nottingham health profile) of patients with cardiovascular pathology (stable angina, myocardial infarction, post infarction myocardial remodeling, chronic heart failure, arrhythmias). We can add that application of Tiotriazolin have social value because it leads to the decrease in mortality and disability of patients with pathology of the cardiovascular system, also decrease in blindness after injury, eye burns, cataracts. The economic efficiency from the Thiotriazolin use is also indicated by reducing the time spent by patients with pathology of the cardiovascular system in the hospital, as a result reducing the state's expenses for the treatment and rehabilitation of this category of patients; also by increase the efficiency of persons whose activities are associated with increased load on the visual analyzer

References

Chekman, I. S., Belenichev, I. F., Gorchakova, N. A., Kucherenko, L. I., Bukhtiyarova, N. V., & Pogotova, G. A. (2014) Antioksidanty: kliniko-farmakologicheskij aspect [Antioxidants: clinical and pharmacological aspects]. Ukrainskyi medychnyi chasopys, 1, 22–28. [in Russian].

Amosova, E. H. (2000) Metabolicheskaya terapiya povrezhdenij miokarda, obuslovlovlennykh ishemiej: novyj podkhod k lecheniyu IBS i serdechnoj nedostatochnosti [Metabolic therapy of myocardial damage due to ischemia: a new approach to the treatment of coronary artery disease and heart failure]. Kyiv. [in Russian].

Bobrov, V. A., Sledzevskaya, I. K., Mkhytarian, L. S., & Parkhomenko, A. N. (1993) Klinicheskoe ispytanie preparata Tiotriazolin u bol'nykh ostrym infarktom miokarda [Clinical trial of the drug Thiotriazolin in patients with acute myocardial infarction]. Kyiv: Farm. komitet MZ Ukrainy. [in Russian].

Zhitnikova, L. M. (2012) Metabolicheskaya terapiya, ili kardiocitoprotekciiya – kak neobkhodimyj komponent kombinirovannoj terapiyi serdechno-sosudistykh zabolevanij [Metabolic therapy, or cardioprotection - as a necessary component of combination therapy for cardiovascular diseases]. Russkij medicinskij zhurnal, 20(4), 137–143. [in Russian].

Kovsh, Ye. V., Bulgak, A. G., Zhiznevskaya, E. E., Shibeko, N. A., Kashitskaya, M. E., & Rabtsevich, V. A. (2010) Tiotriazolin v kompleksnoj terapii pacientov s ostrym koronarnym sindromom [Tiotriazolin in complex therapy of patients with acute coronary syndrome]. Zdravookhranenie, 3, 65–67. [in Russian].

Lollini, V. A., Lysenko, T. F., Andaralova, L. H., & Solov'eva, T. Ya. (2008) Primenenie tiotriazolina u bol'nykh s ostrym infarktom miokarda [Use of thiotriazoline in patients with acute myocardial infarction]. Zaporozhye medical journal, 12(5), 54–55. [in Russian].

Mazur, I. A, Maksimenko, S. F., Belenichev, I. F, & Mikhalchyk, T. S. (1996) Klinichni aspekty zastosuvannia v oftalmolohichnii praktytsi novoho protyishemichnoho antyoksydantnoho preparatu tiotryazolin pry hostrii sudynnii optychnii neiropatii [Clinical aspects of application in the ophthalmic practice of a new anti-ischemic antioxidant preparation tiotriazolin in acute vascular optical neuropathy]. Liky, 6, 133–136. [in Ukrainian].

Mazur, I. A., Belenychev, I. F., & Kucherenko, L. I. (2007) Metabolitotropnye preparaty [Metabolitotropic drugs]. Moscow. [in Russian].

Tolstikova, T. G., Khvostov, M. V., Bryzgalov, A. O., Bukhtiyarova, N. V., Kucherenko, L. I., & Pavlov, S. V. (2010) Nekotorye aspekty metabolitotropnogo dejstviya tiotriazolina pri arterial'noj gipertenzii [Some aspects of the metabolitotropic action of thiotriazolin in arterial hypertension]. Zaporozhye medical journal, 12(5), 74–77. [in Russian].

Stec, V. R., Drogovoz, S. M., Sarbash, T. F., Sal'nikova, S. Yu., Syrcov, V. K., Evdokimov, E. I. (1990) Otchet ob e'ksperimental'nom izuchenii specificheskoj (ranozazhivlyayushchej i gepatoprotektornoj) aktivnosti tiotriazolina [Report on the experimental study of the specific (wound-healing and hepatoprotective) activity of thiotriazoline]. Zaporizhzhia. [in Russian].

Tishkin, V. S., Belenichev, I. F., & Serikov, V. I. (1990) Otchet ob issledovanii obshchetoksicheskogo dejstviya preparata «Rastvor tiotriazolina dlyia vnutrivennykh in'ekcij 2,5%» [Report on the study of the general toxic effect of the drug «Thiotriazoline solution for intravenous injections of 2.5%»]. Zaporizhzhia. [in Russian].

Reshetilov, V. I., Karzov, M. V., & Knysh, E. G. (1994) Otchet ob izuchenii embriotoksicheskikh svojstv novogo lekarstvennogo sredstva tiotriazolina i ego lekarstvennykh form [Report on the study of the embryotoxic properties of thiotriazoline and its dosage forms]. Zaporizhzhia. [in Russian].

Mazur, I. A., Voloshin, N. A., Knysh, E. G., Bondarenko, N. A., & Kovalev, S. P. (1994) Otchet ob izuchenii mutagennykh svojstv novogo lekarstvennogo sredstva «Tiotriazolin» i eho lekarstvennyh form [Report on the study of the mutagenic properties of the new drug «Thiotriazolin» and its dosage forms]. Zaporizhzhia. [in Russian].

Dunaev, V. V., Tishkin, V. S., Stec, V. R., Mazur, I. A., & Knysh, E. H. (1994) Otchet ob e'ksperimental'nom issledovanii antianginal'noj i antiaritmicheskoj aktivnosti preparata Tiotriazolin 2,5% dlia v/v in''ekcij 2 ml [Report on an experimental study of the antianginal and antiarrhythmic activity of the drug Tiotriazolin 2.5% for intravenous injection of 2 ml]. Zaporizhzhia. [in Russian].

Mukhina, I. V. (2009) Otchet o nezavisimoj doklinicheskoj ocenke specificheskoj aktivnosti lekarstvennykh form tiotriazolina (2,5% rastvor dlya in''ekcij tabletki) [Report on the independent preclinical evaluation of the specific activity of the dosage forms of thiotriazoline (2.5% injection and tablets)]. Nizhnij Novgorod. [in Russian].

Frolov, V. M. (2006) Otchet po rezul'tatam otkrytogo issledovaniya po izucheniyu e'ffektivnosti i perenosimosti preparata Tiotriazolin, rastvor dlya in''ekcij 2,5% po 2 ml v ampulakh i tabletki po 0,1 h proizvodstva AO Halychfarm v sravnenii s preparatom E'ssenciale, rastvor dlya in''ekcij 2,5% po 5 ml v ampulakh i kapsuly po 0,3 h proizvodstva firmy «Natterman» u pacientov s khronicheskimi toksicheskimi gepatitami [Report on the results of an open study on the effectiveness and tolerability of the drug Thiotriazolin, 2.5% injection solution for 2 ml in ampoules and 0.1 g tablets produced by JSC Galichpharm compared with Essentiale, 2.5% injection solution 5 ml in ampoules and 0.3 g capsules manufactured by Natterman in patients with chronic toxic hepatitis]. Lugansk [in Russian].

Polivoda, S. N. (2006) Otchet ob otkrytom issledovanii po ocenke e'ffektivnosti i perenosimosti preparata Tiotriazolin proizvodstva AO «Halychfarm» v lechenii ishemycheskoj bolezni serdca [Report on an open study assessing the efficacy and tolerability of the drug Thiotriazolin produced by Halychpharm JSC in the treatment of ischemic heart disease]. Zaporizhzhia. [in Russian].

Dzyak, G. V. (2010) Otchet klinicheskogo issledovaniya «Dvojnoe slepoe, mnogocentrovoe, randomizirovannoye issledovaniye v parallel'nykh gruppakh po ocenke e'ffektivnosti i perenosimosti preparata Tiotriazolin, tabletki proizvodstva OAO «Kievmedpreparat» v sravnenii s placebo u pacientov s IBS, stabil'noj stenokardiej napryazheniya II–III FK», IV faza issledovaniya. Kod klinycheskogo issledovaniya: Thiotriazolin KMP/0607 [Report of the clinical study “Double-blind, multi-center, randomized study in parallel groups to assess the effectiveness and tolerability of the drug Thiotriazolin, tablets manufactured by Kievmedpreparat compared with placebo in patients with coronary artery disease, stable angina, II-III FC”, phase IV research. Clinical research code: Thiotriazolin]. Kyiv. [in Russian].

Zupanec, I. A., & Podpruzhnikov, Yu. V. (2011) Otchet o provedenii klinicheskogo issledovaniya. Klinicheskoe issledovanie po izucheniyu farmakokinetiki lekarstvennogo sredstva tiotriazolin v dvukh lekarstvennykh formakh: tabletki po 0,1 h proizvodstva OAO «Kievmedpreparat» (Ukraina) i Tiotriazolin, rastvor dlya in'ekcij 25 mh/ml, proizvodstva AO «Halychfarm» (Ukraina) pri odnokratnom vvedenii s uchastiem zdorovykh dobrovol'cev [Report on the conduct of a clinical study. A clinical study on the pharmacokinetics of the drug thiotriazolin in two dosage forms: tablets of 0.1 g produced by Kievmedpreparat (Ukraine) and Thiotriazolin, injection solution 25 mg / ml, manufactured by JSC Halychpharm (Ukraine) when administered once healthy volunteers]. Kharkov. [in Russian].

Netyazhenko, V. Z., Mal'chevskaya T. I. (2010) Vozmozhnosti metabolicheskoj terapii v lechenii ishemicheskoj bolezni serdca: opyt dvojnogo slepogo randomizirovannogo mul'ticentrovogo issledovaniya [Possibilities of metabolic therapy in the treatment of coronary heart disease: a double-blind, randomized, multicenter study experience]. Kyiv. [in Russian].

Savchenko, M. A., Teteryukov, A. A., & Savchenko, A. A. (2012) Tiotriazolin kak vazhnyj komponent lecheniya pacientov kardiologicheskogo profilya [Thiotriazolin as an important component in the treatment of cardiac patients]. Kardiologiya v Belarusi, 2, 87–94. [in Russian].

Sytyj, V. P. (2008) E'ffektivnost' Tiotriazolina v lechenii khronicheskoj serdechnoj nedostatochnosti [Thiotriazoline Efficacy in the Treatment of Chronic Heart Failure]. Recept, 5(61), 103–105. [in Russian].

Taschuk, V. K., Solobiukova, N. A., & Makarov, A. A. (2016) E'ffektivnost' preparata Tiotriazolin v kompleksnom lechenii pacientov s ostrym koronarnym sindromom bez pod'ema segmenta ST [Effectiveness of thiotriazolin in a complex treatment of the patients with acute coronary syndrome without ST elevation]. Medicina neotlozhnykh sostoyanij, 8(79), 34–43. [in Russian]. doi: 10.22141/2224-0586.8.79.2016.90371.

(2015) Simpozium «Tiotriazolin: kardioprotekciya s pozicii dokazatel'noj mediciny» v ramkah Rossijskogo nacional'nogo kongressa kardiologov [Symposium «Thiotriazolin: cardioprotection from the position of evidence-based medicine» within the framework of the russian national congress of cardiology]. Rossijskij medicinskij zhurnal, 23(27), 1638–1643. [in Russian].

Mazur, I. A., Kucherenko, L. I., & Belenychev, I. F. (2011) Tiotriazolin, tiodaron v lechenii serdechno-sosudistoj patologii [Thiotriazolin, thiodarone in the treatment of cardiovascular disease]. Zaporizhzhia: Pechatnyj mir. [in Russian].

Topchij, N. V. & Toporkov, A. S. (2015) Vozmozhnosti primeneniya Tiotriazolina v kachestve sredstva metabolicheskoj terapii [The possibility of using Thiotriazoline as a means of metabolic therapy]. Russkij medicinskij zhurnal, 23(15), 890–894. [in Russian].

Belenichev, I. F., Kolesnik, Yu. M., & Kucherenko, L. I. (2008) Racional'naya nejroprotekciya [Rational neuroprotection]. Doneck: Izdatel'skij dom Zaslavskogo. [in Russian].

Belenichev, I., Pavlov, S., Sokolik, E., Mazur, I., Buhtiyarova, N., & Kucherenko, L. (2010) Effect of the Spin Trapping Compound PBN and Thiotriazoline on the Outcome from Experimental Middle Cerebral Artery Occlusion in Rats. Molecular Pharmacology, 1(3), 90–95.

Nahorna, E. A., Chekman, I. S., Belenichev, I. F.,Kolesnik, Yu. M., Abramov, A. V., Gorchakova, N. A., & Levich, S. V. (2016) Molecular and Biochemical Mechanisms of Mitochondrial Dysfunction in Spontaneously Hypertensive Rats on the Background of Carvedilol and Thiotriazoline Usage. Biological Markers and Guided Therapy, 3(1), 73–85. http://dx.doi.org/10.12988/bmgt.2016.637.

How to Cite

1.
Bielenichev IF, Vіzіr VA, Mamchur VY, Kuriata OV. Place of tiotriazoline in the gallery of modern metabolitotropic medicines. Zaporozhye medical journal [Internet]. 2019Feb.8 [cited 2024Apr.25];(1). Available from: http://zmj.zsmu.edu.ua/article/view/155856

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