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Anti-Ischemic Activity of Triamine ALM-802 under Conditions of Endothelial Dysfunction

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Anti-ischemic activity of N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino] ethyl}-1,2-ethanediamine (ALM-802) based on the structure of standard p-FOX inhibitors trimetazidine and ranolazine was studied on the model of endocardial ischemia in intact rats and animals with endothelial dysfunction. Acute endocardial myocardial ischemia was caused by infusion of isoproterenol (20 μg/kg/min intravenously). Endothelial dysfunction in rats was modeled by inducing hyperhomocysteinemia (3 g/kg methionine intragastrically one a day over 7 days). The reference drugs trimetazidine (30 mg/kg, intravenously) and ranolazine 10 mg/kg, intravenously) that were effective only in intact rats. In contrast, ALM-802 (2 mg/kg, intravenously) showed a pronounced anti-ischemic effect in animals with endothelial dysfunction, which suggests that the mechanisms of its cardioprotective action differ from those known for p-FOX inhibitors.

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References

  1. Korokin MV, Pokrovskii MV, Kochkarov VI, Gudyrev OS, Pokrovskaia TG, Korokina LV, Polyanskaya OS. Research of endothelio-and cardioprotective effects of enalapril, lozartan and amlodipin at modelling hyperhomocystein induced endothelial dysfunction. Ross. Med.-Biol. Vestn. 2014;(1):60-65. Russian.

    Google Scholar 

  2. Bhandari B, Subramanian L. Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders. Recent. Pat. Cardiovasc. Drug Discov. 2007;2(1):35-39.

    Article  CAS  Google Scholar 

  3. Fukushima A, Milner K, Gupta A, Lopaschuk GD. Myocardial energy substrate metabolism in heart failure: from pathways to therapeutic targets. Curr. Pharm. Des. 2015;21(25):3654-3664.

    Article  CAS  Google Scholar 

  4. Jaswal JS, Keung W, Wang W, Ussher JR, Lopaschuk GD. Targeting fatty acid and carbohydrate oxidation — a novel therapeutic intervention in the ischemic and failing heart. Biochim. Biophys. Acta. 2011;1813(7):1333-1350.

    Article  CAS  Google Scholar 

  5. Kolwicz SC Jr, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ. Res. 2013;113(5):603-616.

    Article  CAS  Google Scholar 

  6. Lam A, Lopaschuk GD. Anti-anginal effects of partial fatty acid oxidation inhibitors. Curr. Opin. Pharmacol. 2007;7(2):179-185.

    Article  CAS  Google Scholar 

  7. Mamamtavrishvili N, Sanikidze T, Pavliashvili N, Kvirkvelia A, Narsia E. Some aspects of metabolic remodeling of myocard during chronic heart failure. Georgian Med. News. 2008;(154):33-36.

    Google Scholar 

  8. Myrmel Т, Korvald С. New aspects of myocardial oxygen consumption. Invited review. Scand. Cardiovasc. J. 2000; 34(3): 233-241.

    Article  CAS  Google Scholar 

  9. Rupp H, Zarain-Herzberg A, Maisch B. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002;27(7):621-636.

    Article  Google Scholar 

  10. Singer HA, Peach MJ. Calcium- and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta. Hypertension. 1982;4(3, Pt 2):19-25.

    Article  CAS  Google Scholar 

  11. Tousoulis D, Bakogiannis C, Briasoulis A, Papageorgiou N, Androulakis E, Siasos G, Latsios G, Kampoli AM, Charakida M, Toutouzas K, Stefanadis C. Targeting myocardial metabolism for the treatment of stable angina. Curr. Pharm. Des. 2013;19(9):1587-1592.

    PubMed  CAS  Google Scholar 

  12. Tuunanen H, Knuuti J. Metabolic remodelling in human heart failure. Cardiovasc. Res. 2011;90(2):251-257.

    Article  CAS  Google Scholar 

  13. van Bilsen M, Smeets PJ, Gilde AJ, van der Vusse GJ. Metabolic remodelling of the failing heart: the cardiac burn-out syndrome?. Cardiovasc. Res. 2004;61(2):218-226.

    Article  CAS  Google Scholar 

  14. van Bilsen M, van Nieuwenhoven FA, van der Vusse GJ. Metabolic remodelling of the failing heart: beneficial or detrimental? Cardiovasc. Res. 2009;81(3):420-428.

    Article  CAS  Google Scholar 

  15. Yamamoto S, Matsui K, Sasabe M, Ohashi N. Effect of an orally active Na+/H+ exchange inhibitor, SMP-300, on experimental angina and myocardial infarction models in rats. Cardiovasc. Pharmacol. 2002;39(2):234-241.

    Article  CAS  Google Scholar 

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Correspondence to S. A. Kryzhanovskii.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 4, pp. 443-446, April, 2019

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Barchukov, V.V., Tsorin, I.B., Likhosherstov, A.M. et al. Anti-Ischemic Activity of Triamine ALM-802 under Conditions of Endothelial Dysfunction. Bull Exp Biol Med 167, 460–463 (2019). https://doi.org/10.1007/s10517-019-04549-2

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  • DOI: https://doi.org/10.1007/s10517-019-04549-2

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