Nauka innov. 2006, 2(6):77-82

O. O. Moybenko1, R. B. Strutynskyi1, L. M. Yagupolskii2, А. М. Mohort3
1 O.O. Bohomolets Institute of Physiology. NAS of Ukraine, Kyiv
2 Institute of Organic Chemistry, NAS of Ukraine, Kyiv
3 Institute of Pharmacology and Toxicology, AMS of Ukraine, Kyiv


Creation and Preparation of the New Domestic Cardioprotective Drug – Fluorine-Containing Activator of ATP-Dependent Potassium Channels Flokalin

Section: Innovative Projects of National Academy of Sciences of Ukraine
Language: Ukrainian
Abstract: In accordance with the task of the present scientific-research work the technological highly remunerative scheme of synthesis of the new orginative cardioprotective preparation – fluorine-containing KATP channel opener Flokalin has been developed. Investigation of innocence of this substance and drug (tablets) has shown that Flokalin belongs to the class of low toxical compounds. In vitro and in vivo experiments have shown that Flokalin exhibits the dilatation of blood vessels depending on dose; decreases the number of extrasystoles; increases minute volume of blood. The experiment with myocardial ischemi-reperfusion has shown that Flokalin had expressed cardioprotective properties: vastly improves cardiac function during reperfusion (in particular, improves recovery of the contractive activity of miocardium), decreases arrhythmias in ishemic hearts and prevents appearance of reperfusion vasoconstriction. It has been shown that under modeling experimental acute ischemia-reperfusion Flokalin has the antioxidant properties, reduces free radical production, protects the structure of intracellular organels and limits infarct size of heart by 37.5 % comparing with the control group.
Key words: KATP channels, Flokalin, ischemia-reperfusion, cardioprotection.

1. Klebanov B. M., Maljetina I. I., Jagupol's'kyj L. M. ta in. Pat. 17071A Ukrai'na, MPK6 A 61K31/03. N-(1,2,2-trymetylpropil)-N′′-ciano-N′-arylguanidyny z ftorvmisnymy zamisnykamy v aromatychnomu jadri, jaki projavljajut' gipotenzyvnu ta kardiotonichnu diju. N 95041977, Zajav. 26.04.95, Opubl. 31.10.97. Promyslova vlasnist'. 1997, 5:3.1.76 [in Ukrainian].
2. Cavero I., Djellas Y., Guillon J-M. Ischemic miocardial cell protection conferred by the opening of ATP-sensitive potassium channels. Cardiovasc Drags Ther. 1995, 9(2):245–255 [in English].
3. Eells J. T., Henry M. M., Gross G. J., Baker J. E. Increased mitochondrial KATP channel activity during chronic myocardial hypoxia. Is cardioprotection mediated by improved bioenergetics? Circ Res. 2000, 87(10):915–921 [in English].
4. Yagupolskii L. M., Maletina I. I., Klebanov B. M. Fluorine-containing cardiovascular drugs R. Filler et al. Organorluorine compounds and biomedical application. 1993. Elsevier. P. 560 [in English].
5. Eksperymental'ne vyvchennja toksychnoi' dii' potencijnyh likars'kyh zasobiv. Metodychni rekomendacii' Derzhavnogo farmakologichnogo centru MOZ Ukrai'ny. Kyiv: Avicena, 2000 [in Ukrainian].
6. Doklinichni doslidzhennja likars'kyh zasobiv. Metodychni rekomendacii'. Kyiv: Avicena, 2001 [in Ukrainian].
7. Zaugol'nikov S. D., Kochanov M. I., Lojt A. O., Stavchanskij I. I. Jekspressnye metody opredelenija toksichnosti i opasnosti himicheskih veshhestv. M.: Medicina, 1978 [in Russian].
8. Strutyns'kyj R. B., Mojbenko O. O., Jagupol's'kyj L. M., Juz'kiv M. Ja., Kvochina L. I., Shysh A. M. Doslidzhennja kardioprotektornyh efektiv novogo ftormisnogo aktyvatora ATF-zalezhnyh kalijevyh kanaliv. Fiziol. zhurn. 2001, 47(2):16–23 [in Ukrainian].
9. Mojbenko O. O., Juz'kiv M. Ja., Tumanovs'ka L. V., Kocjuruba A. V. Gostra ishemija-reperfuzija miokarda: rol' oksydu azotu. Fiziol. zhurn. 2004, 50(2):34–42 [in Ukrainian].