The mechanisms underlying the antiarrhythmic action of compound trihydrochloride N1-(2,3,4-trimethoxy)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethane-diamine (code ALM-802) were studied in vitro. The experiments were performed on a culture of rat hippocampal neurons. The electrical activity of neurons was recorded by the patch-clamp method in the whole cell configuration. It is shown that the compound ALM-802 effectively blocks potential-dependent Na+ and K+ channels and does not affect the activity of potential-dependent Ca2+ channels. The inhibition of currents through these channels is dose-dependent; the IC50 of Na+ and K+ channels were 94±4 and 67±3 μM, respectively. These findings indicate that compound ALM-802 combines the properties of class I and class III antiarrhythmic agents according to the Vaughan—Williams classification.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update from the GBD 2019 Study. J. Am. Coll. Cardiol. 2020;76(25):2982-3021. doi: https://doi.org/10.1016/j.jacc.2020.11.010
Savina AA, Feyginova SI. Dynamics in incidence of diseases of the circulatory system among adults in the Russian Federation in 2007-2019. Sots. Aspecty Zdorov’ya Naseleniya. 2021;67(2):1-15. Russian. doi: https://doi.org/10.21045/2071-5021-2021-67-2-1
Magadum A, Kishore R. Cardiovascular Manifestations of COVID-19 Infection. Cells. 2020;9(11):2508. doi: https://doi.org/10.3390/cells9112508
Al-Wahaibi K, Al-Wahshi Y, Mohamed Elfadil O. Myocardial injury is associated with higher morbidity and mortality in patients with 2019 novel coronavirus disease (COVID-19). SN Compr. Clin. Med. 2020;2(12):2514-2520. doi: https://doi.org/10.1007/s42399-020-00569-6
Ministry of Health of the Russian Federation: Mortality from Cardiovascular Disease Increased by 6.6% in 10 Months of 2020. VADEMECUM: Healthcare Business Magazine [website]. Russian. URL: https://vademec.ru/news/2020/11/27/minzdrav-smertnost-ot-ssz-za-10-mesyatsev-2020-goda-vyrosla-na-6-6/
Healthcare in Russia. 2021. Statistics Digest. Moscow, 2021. Russian.
Litvinova AA, Silinkina ED, Saphonova KA, Litvinova IA. Evaluation of cardiac rhythm and conduction disorders occurring in patients with COVID-19. Smolensk. Med. Al’manakh. 2021;(3):24-26. Russian.
Sapp JL, Alqarawi W, MacIntyre CJ, Tadros R, Steinberg C, Roberts JD, Laksman Z, Healey JS, Krahn AD. Guidance on minimizing risk of drug-induced ventricular arrhythmia during treatment of COVID-19: a statement from the Canadian Heart Rhythm Society. Can. J. Cardiol. 2020;36(6):948-951. doi: https://doi.org/10.1016/j.cjca.2020.04.003
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. doi: https://doi.org/10.1001/jama.2020.1585
Kryzhanovskii SA, Likhosherstov AM, Tsorin IB, Stolyaruk VN, Vititnova MB, Mokrov GV, Gudasheva TA. Screening of the compounds having cardiotropic activity among the α, ω-diarilmetil derivatives of bis-(ω-aminoalkyl)amines. Farmakokinet. Farmakodinam. 2016;(2):10-13. Russian.
Mokrov GV, Likhosherstov AM, Barchukov VV, Stolyaruk VN, Tsorin IB, Vititnova MB, Kryzhanovskiy SA, Gudasheva TA. Study of methoxy-group position influence on compound ALM-802 cardiotropic activity. Farmakokinet. Farmakodinam. 2019;(1):6-11. Russian. doi: https://doi.org/10.24411/2587-7836-2019-10033
Tsorin IB, Teplov IYu, Zinchenko VP, Vititnova MB, Tsyrlina EM, Yunusov MS, Kryzhanovskii SA. Analysis of electrophysiological mechanisms of N-deacetyllapaconitine monochlorhydrate, the main metabolite of lappaconitine hydrobromide. Bull. Exp. Biol. Med. 2022;173(2):193-198. doi: https://doi.org/10.1007/s10517-022-05522-2
Teplov IYu, Tuleukhanov ST, Zinchenko VP. Regulation of action potential frequency and amplitude by T-type Ca2+ channel during spontaneous synchronous activity of hippocampal neurons. Biophysics. 2018;63(4):566-575. doi: https://doi.org/10.1134/S0006350918040206
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 8, pp. 179-183, August, 2022
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Tsorin, I.B., Teplov, I.Y., Zinchenko, V.P. et al. Mechanisms Underlying the Antiarrhythmic Action of Compound ALM-802. Bull Exp Biol Med 174, 216–220 (2022). https://doi.org/10.1007/s10517-023-05676-7
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-023-05676-7