A comparative study of the anti-ischemic activity of trimetazidine and the compound ALM-802 under conditions of endothelial dysfunction

2019

Фармакокинетика и Фармакодинамика, Vol 0, Iss 2, Pp 23-27 (2019)

Resume. Methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by isoproterenol (20 |jg/kg/ min, i.v.). Endothelial dysfunction was induced, causing hyperhomocysteinemia in rats (methionine 3 g/kg intragastrically 1 time per day for 7 days). The aim. To study on the subendocardial ischemia model in rats the peculiarities of the anti-ischemic action of p-FOX inhibitor trimetazidine and trihydrochloride N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine constructed on the basis of its structure (compound ALM-802) under conditions of endothelial dysfunction. Results. It was shown that in rats with an intact vascular bed and the reference drug trimetazidine (30 mg/kg, i.v.) and the compound ALM-802 (2 mg/kg, i.v.) demonstrated pronounced anti-ischemic activity, while in animals with endothelial dysfunction only the compound ALM-802 was effective. Conclusion. Endothelial dysfunction prevents the implementation of the trimetazidine anti-ischemic action, but does not affect on the compound ALM-802 effect. When studying the anti-ischemic properties of new pharmacological substances, it is advisable to carry out a certain part of the experiments in model experiments that reproduce endothelial dysfunction.

article

Russian

LLC “Publisher OKI”, 2019.

α, ω-диарилметильные производные бис-(ω-аминоалкил)аминов, алм-802, триметазидин, субэндокардиальная ишемия, эндотелиальная дисфункция, р-fox ингибиторы, α, ω-diarylmethyl derivatives of bis-(ω-aminoalkyl) amines, alm-802, trimetazidine, subendocardial ischemia, endothelial dysfunction, p-fox inhibitors, Pharmacy and materia medica, RS1-441