Anti-Ischemic Activity of Triamine ALM-802 under Conditions of Endothelial Dysfunction
- Authors: Barchukov V.V.1, Tsorin I.B.1, Likhosherstov A.M.1, Vititnova M.B.1, Mokrov G.V.1, Gudasheva T.A.1, Kryzhanovskii S.A.1
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Affiliations:
- V. V. Zakusov Research Institute of Pharmacology
- Issue: Vol 167, No 4 (2019)
- Pages: 460-463
- Section: Article
- URL: https://journals.rcsi.science/0007-4888/article/view/241796
- DOI: https://doi.org/10.1007/s10517-019-04549-2
- ID: 241796
Cite item
Abstract
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.
About the authors
V. V. Barchukov
V. V. Zakusov Research Institute of Pharmacology
Email: SAK-538@yandex.ru
Russian Federation, Moscow
I. B. Tsorin
V. V. Zakusov Research Institute of Pharmacology
Email: SAK-538@yandex.ru
Russian Federation, Moscow
A. M. Likhosherstov
V. V. Zakusov Research Institute of Pharmacology
Email: SAK-538@yandex.ru
Russian Federation, Moscow
M. B. Vititnova
V. V. Zakusov Research Institute of Pharmacology
Email: SAK-538@yandex.ru
Russian Federation, Moscow
G. V. Mokrov
V. V. Zakusov Research Institute of Pharmacology
Email: SAK-538@yandex.ru
Russian Federation, Moscow
T. A. Gudasheva
V. V. Zakusov Research Institute of Pharmacology
Email: SAK-538@yandex.ru
Russian Federation, Moscow
S. A. Kryzhanovskii
V. V. Zakusov Research Institute of Pharmacology
Author for correspondence.
Email: SAK-538@yandex.ru
Russian Federation, Moscow