Study of methoxy-group position influence on compound alm-802 cardiotropic activity
https://doi.org/10.24411/2587-7836-2019-10033
Abstract
A new compound ALM-803 (trihydrochloride N1-(3,4,5-trimethoxybenzyl)-N2-{2-[(3,4,5-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine) was synthesized as analog of ALM 802, differing from it by the position of the methoxy groups in the phenyl rings. It is established that this structural change leads to the disappearance of anti-ischemic activity and antiarrhythmic activity on the model of aconitine arrhythmia in rats, but the antiarrhythmic activity on models of chloride-calcium arrhythmia and electrical fibrillation of the heart of rats remained (1 mg/kg, intravenously).
About the Authors
G. V. Mokrov
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
A. M. Likhosherstov
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
V. V. Barchukov
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
V. N. Stolyaruk
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
I. B. Tsorin
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
M. B. Vititnova
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
S. A. Kryzhanovskiy
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
T. A. Gudasheva
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
References
1. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000,86(5):580–588. DOI: 10.1161/01.RES.86.5.580
2. Aldakkak M, Camara AK, Heisner JS, et al. Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial integrity to protect against ischemia reperfusion injury in isolated hearts. Pharmacol Res. 2011,64(4):381–392. DOI: 10.1016/j.phrs.2011.06.018
3. Fragasso G, Salerno A, Spoladore R, et al. Effects of metabolic approach in diabetic patients with coronary artery disease. Curr. Pharm. Des. 2009,15(8):857–862. DOI: 10.2174/138161209787582093
4. Hu B, Li W, Xu T, et al. Evaluation of trimetazidine in angina pectoris by echocardiography and radionuclide angiography: a meta-analysis of randomized, controlled trials. Clin. Cardiol. 2011,34(6):395–400.DOI: 10.1002/clc.20888.
5. Zhang L, Lu Y, Jiang H, et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J. Am. Coll. Cardiol. 2012,59(10),913–922. DOI: 10.1016/j.jacc.2011.11.027
6. Vizzardi E, D’Aloia A, Quinzani F, et al. A focus on antiarrhythmic properties of ranolazine. J. Cardiovasc. Pharmacol. Ther. 2012,17(4):353–356. DOI: 10.1177/1074248412442000
7. 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. J. Cardiovasc. Pharmacol. 2002,39(2):234–241. DOI: 10.1097/00005344-200202000-00010
8. Миронов А.Н. Руководство по проведению доклинических исследований лекарственных средств. Часть 1. – М.: – Гриф и К. 2013. [Mironov AN. Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv. Part 1. Moscow. Grif i K. 2013. (In Russ).].
9. Илюшкина И.А., Берчатова А.Н., Дьяченко И.А. и др. Модели оценки новых противоаритмических препаратов // Биомедицина. – 2012. – № 2. – С. 6–13. [Ilushkina IA, Berchatova AN, Dyachenko IA, et al. Model evaluation of new antiarrhithmic drugs. Biomedicina, 2012,2:6-13. (In Russ).]
10. Харкевич Д.А. Фармакология. – М.: ГЭОТАР-МЕД, 2004. [Kharkevich DA. Farmakologiya. – M.: GEOTAR-MED, 2004. (In Russ).]
Review
For citations:
Mokrov G.V., Likhosherstov A.M., Barchukov V.V., Stolyaruk V.N., Tsorin I.B., Vititnova M.B., Kryzhanovskiy S.A., Gudasheva T.A. Study of methoxy-group position influence on compound alm-802 cardiotropic activity. Pharmacokinetics and Pharmacodynamics. 2019;(1):6-11. (In Russ.) https://doi.org/10.24411/2587-7836-2019-10033
Views:
870
Email this article 